Yubo Fan

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Name: 樊瑜波
Organization: Beihang University
Department: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering
Title:

TOPICS

Co-reporter:Xufeng Niu;Rui Fan;Xiaolin Guo;Tianming Du;Zuo Yang;Qingling Feng
Journal of Materials Chemistry B 2017 vol. 5(Issue 46) pp:9141-9147
Publication Date(Web):2017/11/29
DOI:10.1039/C7TB02223A
Fluid shear stress (FSS) is regarded as a predominant stimulus to bone cells and matrix under physiological conditions. The influence of FSS on mineralization of collagen is explored by exposure to an environment of constant FSS values less than 2.0 Pa. At the designated time points, the apatite/collagen composites were characterized by X-ray diffraction, calcium/phosphorus assay, differential scanning calorimetry, transmission electron microscopy, and selected area electron diffraction. The results show that FSS within a certain range, especially within 1.5 Pa, has a positive effect on collagen mineralization, as illustrated by the enhanced degree of collagen self-assembly, accelerated speed of amorphous calcium phosphate (ACP) formation and transition, and well-organized apatite structure and orientation. Under the condition of FSS, the size of ACP is also well controlled, and the minerals disperse inside collagen fibrils; this leads to intrafibrillar mineralization. These findings are helpful for understanding the mechanism of mineralization in natural bone tissue and deepen the knowledge of biomechanics of this process.
Co-reporter:Zhiyong Qian;Haiping Wang;Xiaoye Tuo;Hongyan Guo;Peng Xu;Donghua Liu;Yen Wei;Haifeng Liu;Ximin Guo
Journal of Materials Chemistry B 2017 vol. 5(Issue 25) pp:4845-4851
Publication Date(Web):2017/06/28
DOI:10.1039/C7TB00802C
Controlling severe hemorrhages remains a challenge. Successful hemorrhage control depends on the speed and quality of blood clot formation. Fast deprivation of water from blood leads to the concentration of blood cells and coagulation factors and thus triggers blood clot formation. This inspired us to develop a new hemostatic material. In this study, we grafted sodium polyacrylate (SPA) onto the backbone of chitosan (CTS) and crosslinked with methacrylic anhydride-modified polyethylene glycol (MAAPEG) to provide a flexible and elastic inter-chain connection between SPA and CTS chains in the presence of a blowing agent to achieve a porous structure. By a simple one-pot reaction, we fabricated a soft, elastic porous xerogel sponge that could reach maximum water absorbency of 180 in less than 200 seconds. This SPA-co-chitosan xerogel sponge demonstrated superior hemostatic properties in thromboelastography (TEG®) test and in a rabbit lethal extremity arterial bleeding model as compared to zeolite granules, kaolin gauze, and chitosan granules. Furthermore, this hemostat worked as a whole to transfer external pressure to the bleeding area and was adhesive to wet wound tissue to seal the bleeding site. In general, the SPA-co-CTS sponge demonstrates a fast and powerful hemostatic effect both in vitro and in vivo, which is superior over the existing commercial products. It might be a promising first-aid device for severe hemorrhage control.
Co-reporter:Yi Yang;Xili Ding;Tongqiang Zou;Ge Peng;Haifeng Liu
RSC Advances (2011-Present) 2017 vol. 7(Issue 13) pp:7954-7963
Publication Date(Web):2017/01/20
DOI:10.1039/C6RA26807B
Electroactive scaffolds which can carry electrical stimulation to the cells growing on them have attracted more and more attention in recent years. In this study, a conductive fibrous scaffold made of silk fibroin (SF) and graphene was developed using electrospinning techniques. The chemical structural characterization of the obtained scaffolds confirmed the presence of graphene in the fibrous scaffolds. The surface morphologies, mechanical and electrochemical properties and cytocompatibility of the scaffolds were evaluated. The average diameters of the G/SF fibrous scaffolds increased with the addition of graphene until the content of graphene reached 4%. The G/SF scaffolds exhibited improved thermal stability with the addition of graphene, which confirmed that they were more crystalline than pure SF scaffolds. The 3% G/SF fibrous scaffolds showed improved electroactivity and mechanical properties. In addition, they could support the growth and expansion of rat bone mesenchymal stem cells (rBMSCs) based on cell morphology, viability and proliferation studies in vitro. Thus, all the data in this study suggested that the 3% G/SF scaffolds might represent an adequate substrate to successfully scaffold electroactive tissue during regeneration or engineering.
Co-reporter:Zhongjun Mo;Qi Li;Zhiwei Jia;Jiemeng Yang;Duo Wai-Chi Wong
European Spine Journal 2017 Volume 26( Issue 4) pp:
Publication Date(Web):
DOI:10.1007/s00586-016-4777-9
Co-reporter:Zhongjun Mo;Qi Li;Zhiwei Jia;Jiemeng Yang;Duo Wai-Chi Wong
European Spine Journal 2017 Volume 26( Issue 1) pp:
Publication Date(Web):
DOI:10.1007/s00586-016-4799-3
Co-reporter:Danyan Wang;Yan Sun;Xili Ding;Ge Peng
Journal of Medical and Biological Engineering 2017 Volume 37( Issue 5) pp:750-759
Publication Date(Web):16 June 2017
DOI:10.1007/s40846-017-0249-x
To design functional vascular grafts, it is essential to explore the interactions between endothelial cells and the surface of substrate biomaterials. The present study thus aimed at evaluating the influence of micropatterned silk fibroin films on human umbilical vein endothelial cell (HUVEC) behaviors including adhesion, migration, proliferation, and protein expressions. Silk fibroin films with different grafting micropatterns (10 μm × 10 μm, 20 μm × 20 μm, 20 μm × 30 μm, 40 μm × 40 μm) were prepared by soft-lithographic technique. HUVECs were shown to attach and grow well on the silk fibroin films. The results indicated that the 10 × 10 and 40 × 40 gratings induced higher proliferation rates as compared to the 20 × 20 and 20 × 30 groups. However, the increased orientation and alignment degree and stronger protein expressions (CD31, VWF and Vinculin) were observed on the 20 × 20 and 20 × 30 groups. Overall, this study suggested that the HUVEC behaviors could be regulated in vitro by different micropattern topographies. The micropatterned silk fibroin films may offer a potential improvement for the development of functional vascular grafts.
Co-reporter:Sicong Wang, Lizhen Wang, Yawei Wang, Chengfei Du, ... Yubo Fan
Medical Engineering & Physics 2017 Volume 39(Volume 39) pp:
Publication Date(Web):1 January 2017
DOI:10.1016/j.medengphy.2016.10.004
•We develop a finite element model of L1–L5 spine and a vibration dynamic model.•A new rehabilitation therapy that combines traction and vibration is investigated.•Combined therapy is more effective than traction alone in terms of biomechanics.•This therapy could help decompress the discs/nerves and thus relieve low back pain.•Patients with grade 1 degeneration (41–50 years) are able to obtain better results.In recent years, a combination of traction and vibration therapy is usually used to alleviate low back pain (LBP) in clinical settings. Combining head-down tilt (HDT) traction with vibration was demonstrated to be efficacious for LBP patients in our previous study. However, the biomechanics of the lumbar spine during this combined treatment is not well known and need quantitative analysis. In addition, LBP patients have different grades of degeneration of the lumbar spinal structure, which are often age related. Selecting a suitable rehabilitation therapy for different age groups of patients has been challenging. Therefore, a finite element (FE) model of the L1–L5 lumbar spine and a vibration dynamic model are developed in this study in order to investigate the biomechanical effects of the combination of HDT traction and vibration therapy on the age-related degeneration of the lumbar spine. The decrease of intradiscal pressure is more effective when vibration is combined with traction therapy. Moreover, the stresses on the discs are lower in the “traction + vibration” mode than the “traction-only” mode. The stress concentration at the posterior part of nucleus is mitigated after the vibration is combined. The disc deformations especially posterior disc radial retraction is improved in the “traction + vibration” mode. These beneficial effects of this therapy could help decompress the discs and spinal nerves and therefore relieve LBP. Simultaneously, patients with grade 1 degeneration (approximately 41–50 years old) are able to achieve better results compared with other age groups. This study could be used to provide a more effective LBP rehabilitation therapy.
Co-reporter:Xianghui Gong, Jie Yao, Hongping He, Xixi Zhao, Xiaoyi Liu, Feng Zhao, Yan Sun, Yubo Fan
Journal of the Mechanical Behavior of Biomedical Materials 2017 Volume 74(Volume 74) pp:
Publication Date(Web):1 October 2017
DOI:10.1016/j.jmbbm.2017.04.028
Assuring cell adhesion to an underlying biomaterial surface under blood flow is vital to functional vascular grafts design. In vivo endothelial cells (ECs) are located under the microenvironment of both surface topography of the basement membrane and the mechanical loading resulting from blood flow. Both topographical and mechanical factors should thus be considered when designing vascular grafts to enhance the flow-resistant EC adhesion. This study aims to investigate effects of integrating biomaterial surface topography and flow on EC adhesion, which was a deficit in previous studies. Human umbilical vein endothelial cells (HUVECs) were cultured on different fibronectin (FN) micropatterns parallel or perpendicular to the flow direction and exposed to sustained flow with physiological levels of shear stress (15 dyne/cm2). We demonstrated that micropattern alignment parallel to the flow direction enhanced flow-resistant EC adhesion, while micropattern alignment perpendicular to the flow direction attenuated it. Experimental and numeric modeling analysis underlined that the flow-induced mechanic distribution on the surface of cells that were aligned on the micropatterned surfaces and the subsequent cytoskeleton rearrangement were responsible for the significant difference in EC adhesion. Furthermore, pressure on the surface of cells that were aligned on the micropatterned surfaces induced by flow provided a more critical role in EC adhesion than shear stress. These findings highlight the importance of proper combination of topographical and flow cues in enhancement of EC adhesion and may suggest new strategies for designing functional vascular grafts.
Co-reporter:Wen-Ting Li;Yun-Fei Huang;Lian-Wen Sun
Microgravity Science and Technology 2017 Volume 29( Issue 1-2) pp:107-114
Publication Date(Web):2017 February
DOI:10.1007/s12217-016-9530-9
Despite the fast development of manned space flight, the mechanism and countermeasures of weightlessness osteoporosis in astronauts are still within research. It is accepted that unloading has been considered as primary factor, but the precise mechanism is still unclear. Since bone’s interstitial fluid flow (IFF) is believed to be significant to nutrient supply and waste metabolism of bone tissue, it may influence bone quality as well. We investigated IFF’s variation in different parts of body (included parietal bone, ulna, lumbar, tibia and tailbone) of rats using a tail-suspended (TS) system. Ten female Sprague-Dawley (SD) rats were divided into two groups: control (CON) and tail-suspension (TS) group. And after 21 days’ experiment, the rats were injected reactive red to observe lacuna’s condition under a confocal laser scanning microscope. The variations of IFF were analyzed by the number and area of lacuna. Volumetric bone mineral density (vBMD) and microarchitecture of bones were evaluated by micro-CT. The correlation coefficients between lacuna’s number/area and vBMD were also analyzed. According to our experimental results, a 21 days’ tail-suspension could cause a decrease of IFF in lumbar, tibia and tailbone and an increase of IFF in ulna. But in parietal bone, it showed no significant change. The vBMD and microarchitecture parameters also decreased in lumbar and tibia and increased in ulna. But in parietal bone and tailbone, it showed no significant change. And correlation analysis showed significant correlation between vBMD and lacuna’s number in lumbar, tibia and ulna. Therefore, IFF decrease may be partly contribute to bone loss in tail-suspended rats, and it should be further investigated.
Co-reporter:Wen-Ting Li;Yun-Fei Huang;Lian-Wen Sun
Microgravity Science and Technology 2017 Volume 29( Issue 1-2) pp:107-114
Publication Date(Web):2017 February
DOI:10.1007/s12217-016-9530-9
Despite the fast development of manned space flight, the mechanism and countermeasures of weightlessness osteoporosis in astronauts are still within research. It is accepted that unloading has been considered as primary factor, but the precise mechanism is still unclear. Since bone’s interstitial fluid flow (IFF) is believed to be significant to nutrient supply and waste metabolism of bone tissue, it may influence bone quality as well. We investigated IFF’s variation in different parts of body (included parietal bone, ulna, lumbar, tibia and tailbone) of rats using a tail-suspended (TS) system. Ten female Sprague-Dawley (SD) rats were divided into two groups: control (CON) and tail-suspension (TS) group. And after 21 days’ experiment, the rats were injected reactive red to observe lacuna’s condition under a confocal laser scanning microscope. The variations of IFF were analyzed by the number and area of lacuna. Volumetric bone mineral density (vBMD) and microarchitecture of bones were evaluated by micro-CT. The correlation coefficients between lacuna’s number/area and vBMD were also analyzed. According to our experimental results, a 21 days’ tail-suspension could cause a decrease of IFF in lumbar, tibia and tailbone and an increase of IFF in ulna. But in parietal bone, it showed no significant change. The vBMD and microarchitecture parameters also decreased in lumbar and tibia and increased in ulna. But in parietal bone and tailbone, it showed no significant change. And correlation analysis showed significant correlation between vBMD and lacuna’s number in lumbar, tibia and ulna. Therefore, IFF decrease may be partly contribute to bone loss in tail-suspended rats, and it should be further investigated.
Co-reporter:Xufeng Niu, Siqian Chen, Feng Tian, Lizhen Wang, Qingling Feng, Yubo Fan
Materials Science and Engineering: C 2017 Volume 70, Part 2(Volume 70, Part 2) pp:
Publication Date(Web):1 January 2017
DOI:10.1016/j.msec.2016.04.095
•ACP is prepared using a wet chemical method.•The conversion of crystal morphology and structure occurs mainly within the initial 9 h.•The calcium and orthophosphate ions release sustains over 14 d.The aim of this study is to investigate the calcium and orthophosphate ions release during the transformation of amorphous calcium phosphate (ACP) to hydroxyapatite (HA) in aqueous solution. The ACP is prepared by a wet chemical method and further immersed in the distilled water for various time points till 14 d. The release of calcium and orthophosphate ions is measured with calcium and phosphate colorimetric assay kits, respectively. The transition of ACP towards HA is detected by x-ray diffraction (XRD), transmission electron microscopy (TEM), and fourier transform infrared spectroscopy (FTIR). The results indicate that the morphological conversion of ACP to HA occurs within the first 9 h, whereas the calcium and orthophosphate ions releases last for over 7 d. Such sustained calcium and orthophosphate ions release is very useful for ACP as a candidate material for hard tissue regeneration.
Co-reporter:Fang Zhou, Xiaoling Jia, Yang Yang, Qingmao Yang, Chao Gao, Suli Hu, Yunhui Zhao, Yubo Fan, Xiaoyan Yuan
Acta Biomaterialia 2016 Volume 43() pp:303-313
Publication Date(Web):1 October 2016
DOI:10.1016/j.actbio.2016.07.048

Abstract

As manipulation of gene expression by virtue of microRNAs (miRNAs) is one of the emerging strategies for cardiovascular disease remedy, local delivery of miRNAs to a specific vascular tissue is challenging. In this work, we developed an efficient delivery system composed of electrospun fibrous membranes and target carriers for the intracellular delivery of miRNA-126 (miR-126) to vascular endothelial cells (VECs) in the local specific vascular environment. A bilayer vascular scaffold was specially prepared via emulsion electrospinning of poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) (PELCL) and dual-power electrospinning of poly(ε-caprolactone) (PCL) and gelatin. The inner layer of PELCL, which was loaded with complexes of miR-126 in REDV peptide-modified trimethyl chitosan-g-poly(ethylene glycol), regulated the response of VECs, while the outer layer of PCL/gelatin contributed to the mechanical stability. Biological activities of the miR-126-loaded electrospun membranes were evaluated by cell proliferation and SPRED-1 expression of a miR-126 target gene. By encapsulating targeting complexes of miR-126 in the electrospun membranes, a sustained release profile of miRNA was obtained for 56 days. Significant down-regulation of SPRED-1 gene expression in VECs was detected on day 3, and it was found that miR-126 released from the electrospun membranes accelerated VEC proliferation in the first 9 days. The bilayer vascular scaffold loaded with miR-126 complexes could also improve endothelialization in vivo. These results demonstrated the potential of this approach towards a new and more effective delivering system for local delivery of miRNAs to facilitate blood vessel regeneration.

Statement of Significance

Tissue engineering of small-diameter blood vessels is still challenging because of thrombosis and low long-term patency. The manipulation of gene expression by miRNAs could be a novel strategy in vascular regeneration. Here, we report an efficient delivery system of electrospun fibrous scaffold combined with REDV peptide-modified trimethyl chitosan for targeted intracellular delivery of miR-126 to VECs in the local vascular environment. Results exhibited that miR-126 released from the electrospun membrane could modulate VEC proliferation via down-regulation of SPRED-1 gene expression. The electrospun scaffolds loaded with target-delivery carriers may serve as an ideal platform for local delivery of miRNAs in the vascular tissue engineering.

Co-reporter:Fang Zhou, Xiaoling Jia, Qingmao Yang, Yang Yang, Yunhui Zhao, Yubo Fan and Xiaoyan Yuan  
Biomaterials Science 2016 vol. 4(Issue 5) pp:849-856
Publication Date(Web):08 Apr 2016
DOI:10.1039/C5BM00629E
Manipulation of gene expression by means of microRNAs (miRNAs) is one of the emerging strategies to treat cardiovascular and cancer diseases. Nevertheless, efficient delivery of miRNAs to a specific vascular tissue is limited. In this work, a short peptide Arg-Glu-Asp-Val (REDV) was linked to trimethyl chitosan (TMC) via a bifunctional poly(ethylene glycol) (PEG) linker for the targeted delivery of microRNA-126 (miRNA-126) to vascular endothelial cells (VECs). The morphology, serum stability and cytotoxicity of the polyplex/miRNA complexes, namely, TMC/miRNA, TMC-g-PEG/miRNA and TMC-g-PEG-REDV/miRNA, were investigated along with the cellular uptake, proliferation and in vitro miRNA transfection efficiency. By REDV modification, the TMC-g-PEG-REDV/miRNA complex showed negligible cytotoxicity, increased expression of miRNA-126 and enhanced VEC proliferation compared with the TMC/miRNA and TMC-g-PEG/miRNA complexes. In particular, the approaches adopted for the miRNA delivery and targeted peptide REDV modification promote the selective uptake and the growth of VECs over vascular smooth muscle cells. It was suggested that the REDV peptide-modified TMC-g-PEG polyplex could be potentially used as a miRNA carrier in artificial blood vessels for rapid endothelialization.
Co-reporter:Meng Guo, Zhaowei Chu, Jie Yao, Wentao Feng, Yuxing Wang, Lizhen Wang, Yubo Fan
Polymer Degradation and Stability 2016 Volume 124() pp:95-100
Publication Date(Web):February 2016
DOI:10.1016/j.polymdegradstab.2015.12.019
The inhomogeneous stress distribution of biodegradable stents after implantation affects the local degradation rate of the stents, leading to stress concentration and hence stent fracture. The quantitative relationship between the tensile stress and degradation rate of stent polymer is first investigated in this work. To implement the study, an in vitro degradation of poly(l-lactide-co-glycolide) (PLGA) membranes was incubated in deionized water under different applied tensile stress levels from 0.1 MPa to 0.5 MPa. By a special designed device, the tensile stress level can be maintained constant during degradation. The mass loss and mechanical properties of the membranes during the degradation were sampled each week until the membranes broke. The experimental results showed that over a range of tensile stress, higher tensile stress might lead to quicker loss of mechanical properties. Specifically, remarkable decreases of elastic modulus and tensile strength in 0.5 MPa group were observed. As the magnitude of tensile stress increased, more mass loss was observed in the loaded groups. In conclusion, the mass loss rate and mechanical properties of PLGA was sensitive to the tensile stress level during the in vitro degradation. The load dependency of our data demonstrates the importance of quantifying the effects of tensile stress on the degradation of biodegradable polymers. Moreover, this quantification model could be used as a prediction tool for the optimization of biodegradable polymer stents.
Co-reporter:Xufeng Niu, Liyang Wang, Feng Tian, Lizhen Wang, Ping Li, Qingling Feng, Yubo Fan
Journal of the Mechanical Behavior of Biomedical Materials 2016 Volume 54() pp:131-140
Publication Date(Web):February 2016
DOI:10.1016/j.jmbbm.2015.09.024
The contribution of fluid shear stress (FSS) on the conversion of amorphous calcium phosphate (ACP) to bone apatite is investigated. The ACP precursors are prepared by using a wet-chemistry method and further exposed to the constant FSS environment with values of 0.5, 1.0, 1.5, and 2.0 Pa. At the designated time points, the apatites are characterized by transmission electron microscopy, X-ray diffraction, and inductively coupled plasma-mass spectroscopy. The results show that, the low FSS (≤1.0 Pa) has positive effects on the transition of ACP, characterized by the accelerated crystallization velocity and the well-organized calcium-deficient hydroxyapatite (CDHA) structure, whereas the high FSS (>1.0 Pa) has negative effects on this conversion process, characterized by the poor CDHA crystal morphologies and the destroyed structures. The bioactivity evaluations further reveal that, compared with the FSS-free group, the CDHA prepared under 1.0 Pa FSS for 9 h presents the more biocompatible features with pre-osteoblast cells. These results are helpful for understanding the mechanism of apatite deposition in natural bone tissue.
Co-reporter:Danyu Yao, Haifeng Liu and Yubo Fan  
RSC Advances 2016 vol. 6(Issue 66) pp:61402-61409
Publication Date(Web):15 Jun 2016
DOI:10.1039/C6RA10670F
Silk fibroin (SF) is a promising biomaterial and has been widely used in tissue engineering. However, most of the currently used fabrication techniques require the use of organic solvents that cannot be removed thoroughly. The residual organic solvents reduce the proliferation capacity of cells. In this study, we developed water-insoluble SF scaffolds by a simple temperature induced method without the addition of organic or inorganic substances. Temperature was used to tune the self-assembly of SF during the freezing process, which resulted in water stable porous scaffolds directly. Compared with the traditional methanol treated scaffolds, the current scaffolds presented a less crystalline structure, lower elasticity modulus and faster degradation rate. In addition, human umbilical vein endothelial cells (HUVECs) showed an enhanced adhesion capacity, better spreading morphology and a faster proliferation rate on the scaffold. Investigation of the scaffold formation mechanism revealed that the performance of the current scaffold was dominated by the storage time and temperature, which tuned the self-assembly process of SF by controlling the molecular activity and contributed to the low crystallinity of the structure and water-insolubility. The results indicated that this low crystallinity scaffold holds great promise as a candidate for soft tissue repair materials.
Co-reporter:Xili Ding, Chengqi Wu, Tong Ha, Lizhen Wang, Yan Huang, Hongyan Kang, Yingying Zhang, Haifeng Liu and Yubo Fan  
RSC Advances 2016 vol. 6(Issue 23) pp:19463-19474
Publication Date(Web):12 Feb 2016
DOI:10.1039/C5RA26752H
The periosteum plays an indispensable role in both bone formation and bone defect healing. The purpose of this study was to construct a functional periosteum in vitro. We developed a simple technology to generate a hydroxyapatite (HA)-containing silk fibroin nanofibrous scaffold as a potential substitute for periosteum. The chemical structural characteristics of the scaffold were evaluated and the results confirmed the presence of HA in the scaffolds. In addition, the Young's modulus of silk fibroin–hydroxyapatite (SF/HA) scaffolds increased with the increasing content of HA. Rat bone marrow derived mesenchymal stem cells (rBMSCs) were cultured on the scaffolds for 7, 14, and 21 days without adding any osteogenic factors. Cell proliferation assay and cell morphology observation indicated that 30% SF/HA scaffolds exhibited good cell attachment and proliferation. In addition, differentiation of rBMSCs into osteogenic lineage was more actively exhibited on 30% SF/HA scaffolds, as evident by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for osteoblast-related gene markers (e.g., COL1A1, ALP, and Runx2), ALP activities, mineral deposits and immunocytochemical evaluations of osteoblast-related extracellular matrix components (e.g., OPN, ONN, and OCN). All the data in this study suggested that 30% SF/HA scaffolds had great potential as osteogenesis promoting scaffolds for constructing tissue-engineered periosteum.
Co-reporter:Yingying Zhang;He Gong;Yan Sun;Yan Huang
Journal of Biomedical Materials Research Part A 2016 Volume 104( Issue 5) pp:1143-1152
Publication Date(Web):
DOI:10.1002/jbm.a.35648

Abstract

Numerous studies have shown that surface topography can promote cell–substrate associations and deeply influence cell fate. The intracellular mechanism or how micro- or nano-patterned extracellular signal is ultimately linked to activity of nuclear transcription factors remains unknown. It has been reported that Yes-associated protein (YAP) can respond to extracellular matrix microenvironment signals, thus regulates stem cell differentiation process. We propose that YAP may play a role in mediating the topography induced cell differentiation. To this end, we fabricated polydimethylsiloxane (PDMS) micropatterns with grid topology (GT) (3 μm pattern width, 2 μm pattern interval length, 7 μm pattern height); nonpatterned PDMS substrates were used as the planar controls. The MC3T3-E1 cells were then cultured on these surfaces, respectively, in osteogenic inducing medium. Cell differentiation in terms of osteogenesis related gene expression, protein levels, alkaline phosphatase activity and extracellular matrix mineralization was assessed. It was shown that the cells on GT surfaces had stronger osteogenesis capacity. In addition, expression level of YAP was increased when MC3T3-E1 cells grew on GT substrates, which was similar to the levels of osteogenic differentiation markers. It was also shown that YAP knockdown attenuated GT substrates-induced MC3T3-E1 differentiation, which reduced the osteogenic differentiation effect of the GT substrates. Collectively, our findings indicate that GT substrates-induced MC3T3-E1 differentiation may be associated with YAP. This paper provides new target points for transcriptional mechanism research of microenvironment induced cell differentiation and a useful approach to obtain more biofunctionalization scaffolds for tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1143–1152, 2016.

Co-reporter:Xiaoming Li;Jianrong Wei;Katerina E. Aifantis;Qingling Feng;Fu-Zhai Cui;Fumio Watari
Journal of Biomedical Materials Research Part A 2016 Volume 104( Issue 5) pp:1285-1296
Publication Date(Web):
DOI:10.1002/jbm.a.35654

Abstract

It is generally recognized that nanoparticles possess unique physicochemical properties that are largely different from those of conventional materials, specifically the electromagnetic properties of magnetic nanoparticles (MNPs). These properties have attracted many researchers to launch investigations into their potential biomedical applications, which have been reviewed in this article. First, common types of MNPs were briefly introduced. Then, the biomedical applications of MNPs were reviewed in seven parts: magnetic resonance imaging (MRI), cancer therapy, the delivery of drugs and genes, bone and dental repair, tissue engineering, biosensors, and in other aspects, which indicated that MNPs possess great potentials for many kinds of biomedical applications due to their unique properties. Although lots of achievements have been obtained, there is still a lot of work to do. New synthesis techniques and methods are still needed to develop the MNPs with satisfactory biocompatibility. More effective methods need to be exploited to prepare MNPs-based composites with fine microstructures and high biomedical performances. Other promising research points include the development of more appropriate techniques of experiments both in vitro and in vivo to detect and analyze the biocompatibility and cytotoxicity of MNPs and understand the possible influencing mechanism of the two properties. More comprehensive investigations into the diagnostic and therapeutic applications of composites containing MNPs with “core-shell” structure and deeper understanding and further study into the properties of MNPs to reveal their new biomedical applications, are also described in the conclusion and perspectives part. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1285–1296, 2016.

Co-reporter:Tongqiang Zou;Jiabing Fan;Armita Fartash;Haifeng Liu
Journal of Biomedical Materials Research Part A 2016 Volume 104( Issue 5) pp:1297-1314
Publication Date(Web):
DOI:10.1002/jbm.a.35660

Abstract

Vascular regeneration is known to play an essential role in the repair of injured tissues mainly through accelerating the repair of vascular injury caused by vascular diseases, as well as the recovery of ischemic tissues. However, the clinical vascular regeneration is still challenging. Cell-based therapy is thought to be a promising strategy for vascular regeneration, since various cells have been identified to exert important influences on the process of vascular regeneration such as the enhanced endothelium formation on the surface of vascular grafts, and the induction of vessel-like network formation in the ischemic tissues. Here are a vast number of diverse cell-based strategies that have been extensively studied in vascular regeneration. These strategies can be further classified into three main categories, including cell transplantation, construction of tissue-engineered grafts, and surface modification of scaffolds. Cells used in these strategies mainly refer to terminally differentiated vascular cells, pluripotent stem cells, multipotent stem cells, and unipotent stem cells. The aim of this review is to summarize the reported research advances on the application of various cells for vascular regeneration, yielding insights into future clinical treatment for injured tissue/organ. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1297–1314, 2016.

Co-reporter:Xiaoming Li;Tianxiao Zhao;Lianwen Sun;Katerina E. Aifantis;Qingling Feng;Fuzhai Cui;Fumio Watari
Journal of Biomedical Materials Research Part A 2016 Volume 104( Issue 1) pp:322-339
Publication Date(Web):
DOI:10.1002/jbm.a.35537

Abstract

As their name suggests, conductive nanomaterials (CNMs) are a type of functional materials, which not only have a high surface area to volume ratio, but also possess excellent conductivity. Thus far, CNMs have been widely used in biomedical applications, such as effectively transferring electrical signals, and providing a large surface area to adsorb proteins and induce cellular functions. Recent works propose further applications of CNMs in biosensors, tissue engineering, neural probes, and drug delivery. This review focuses on common types of CNMs and elaborates on their unique properties, which indicate that such CNMs have a potential to develop into a class of indispensable biomaterials for the diagnosis and therapy of human diseases. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 322–339, 2016.

Co-reporter:Xiaoming Li;Zheng Wang;Tianxiao Zhao;Bo Yu;Qingling Feng;Fu-zhai Cui;Fumio Watari
Journal of Biomedical Materials Research Part A 2016 Volume 104( Issue 9) pp:2117-2125
Publication Date(Web):
DOI:10.1002/jbm.a.35743

Abstract

This study provided a new method to in vitro evaluate the biocompatibility of nanoscaled scaffolds for tissue engineering with neutrophils other than ordinary cell culture. The neutrophils were separated from human peripheral blood of healthy subjects. In vitro degradation product of nanohydroxyapatite/collagen (nHAC), nanohydroxyapatite/collagen/poly (L-lactic acid) (nHACP), and nHACP reinforced by chitin fibers (nHACP/CF) in the D-Hank's Balanced Salt Solution (D-HBSS) was used as the testing solution, which was thereafter mixed with the neutrophils. It was shown that the cell survival rate in the testing solutions had no significant difference from that in the D-HBSS (control). However, from both gene and protein expression levels, the lactate dehydrogenase and tumor necrosis factor-alpha of the neutrophils in the nHACP/CF testing solution were found lowest during the whole testing period; the main reasons of which might be that the calcium release rate of the scaffold was slowest and that the pH value of its degradation solution was nearest to that of human body. Moreover, in vivo experiments showed that most inflammation reactions happened for nHAC and poly (L-lactic acid) groups, while the least inflammation reactions happened for nHACP/CF group in the subcutaneous dorsum of mice at 2 weeks after the surgery, which confirmed the in vitro findings. These results indicated that the pH value and the certain metal iron concentration of the nanoscaled scaffold degradation solution should be two important factors that significantly affect its biocompatibility. This study provides a simple and effective biocompatibility test method for biodegradable nanoscaled tissue engineering scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2117–2125, 2016.

Co-reporter:Zhaowei Chu;Quan Zheng;Meng Guo;Jie Yao;Peng Xu;Wentao Feng;Yongzhao Hou;Gang Zhou;Lizhen Wang;Xiaoming Li
Journal of Biomedical Materials Research Part A 2016 Volume 104( Issue 9) pp:2315-2324
Publication Date(Web):
DOI:10.1002/jbm.a.35766

Abstract

Poly(lactide-co-glycolide) acid (PLGA) has been widely used as a biodegradable polymer material for coating stents or fabricating biodegradable stents. Its mechanism of degradation has been extensively investigated, especially with regard to how tensile and compressive loadings may affect the in vitro degradation of PLGA. Fluid shear stress is also one of the most important factors in the development of atherosclerosis and restenosis. But the effect of fluid shear stress on the degradation process is still unclear. The purpose of this study was to characterize the in vitro degradation of PLGA membranes that experienced different fluid shear stresses in 150 mL of deionized water at 37°C for 20 days. Particular emphasis was given to changes in the viscosity of the degradation solution, as well as the mechanical and morphological properties of the samples. The viscosity of the degradation solution with the mechanical loaded specimens was more severely affected than that of the control group. Increasing the fluid shear stress could accelerate the loss of the ultimate strength of PLGA membranes while it slowed down the change of the tensile elastic modulus in the early period. With regard to morphology, the surface roughness was more obviously reduced in the loaded groups. This indicated that the fluid shear stress could affect the in vitro degradation of PLGA membranes. Therefore, this study could help improve the design of PLGA membranes for biomedical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2016.

Co-reporter:Fang Zhou, Xiaoling Jia, Yang Yang, Qingmao Yang, Chao Gao, Yunhui Zhao, Yubo Fan, Xiaoyan Yuan
Materials Science and Engineering: C 2016 Volume 68() pp:623-631
Publication Date(Web):1 November 2016
DOI:10.1016/j.msec.2016.06.036
•A series of peptide-modified PELCL electrospun membranes were prepared.•Hemocompatibility of the membranes was greatly improved by the modification.•QK-modified PELCL membrane promoted VECs proliferation more significantly.•REDV-modified PELCL membrane was the most favorable for VEC adhesion.The efficiency of biomaterials used in small vascular repair depends greatly on their ability to interact with vascular endothelial cells (VECs). Rapid endothelialization of the vascular grafts is a promising way to prevent thrombosis and intimal hyperplasia. In this work, modification of electrospun membranes of poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) (PELCL) by three different peptides for regulation of VECs were studied in order to obtain ideal bioactive biomaterials as small diameter vascular grafts. QK (a mimetic peptide to vascular endothelial growth factor), Arg-Glu-Asp-Val (REDV, a specific adhesive peptide to VECs) and Val-Ala-Pro-Gly (VAPG, a specific adhesive peptide to vascular smooth muscle cells) were investigated. Surface properties of the modified membranes and the response of VECs were verified. It was found that protein adsorption and platelet adhesion were effectively suppressed with the introduction of QK, REDV or VAPG peptides on the PELCL electrospun membranes. Both QK- and REDV-modified electrospun membranes could accelerate the proliferation of VECs in the first 9 days, and the QK-modified electrospun membrane promoted cell proliferation more significantly than the REDV-modified one. The REDV-modified PELCL membrane was the most favorable for VECs adhesion than QK- and VAPG-modified membranes. It was suggested that QK- or REDV-modified PELCL electrospun membranes may have great potential applications in cardiovascular biomaterials for rapid endothelialization in situ.
Co-reporter:Xili Ding, Xing Wei, Yan Huang, Changdong Guan, Tongqiang Zou, Shuo Wang, Haifeng Liu and Yubo Fan  
Journal of Materials Chemistry A 2015 vol. 3(Issue 16) pp:3177-3188
Publication Date(Web):06 Mar 2015
DOI:10.1039/C5TB00046G
Demineralized bone matrix (DBM) has been widely used for bone regeneration due to its osteoinductivity and osteoconductivity. However, the use of DBM powder is limited due to the difficulties in handling, the tendency to migrate from graft sites and the lack of stability after surgery. In this study, a mechanically stable, salt-leached porous silk fibroin carrier was used to improve the handling properties of DBM powder and to support the attachment, proliferation and osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). The DBM-silk fibroin (DBM/SF) scaffolds were fabricated with different contents of DBM powder (0%, 10%, 20%, 40% and 80% DBM/SF scaffolds). It was found that the DBM/SF scaffolds could form a stable composite preventing the migration of DBM powder. Moreover, the microarchitecture and mechanical properties of the scaffolds were influenced by the DBM powder. rBMSCs were seeded on the DBM/SF scaffolds and cultured for 14 days. Cell proliferation assays and cell morphology observations indicated that 20% DBM/SF scaffolds exhibited good cell attachment and proliferation. In addition, compared with the other groups, the cellular function was more actively exhibited on 20% DBM/SF scaffolds, as evident by the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for osteoblast-related gene markers (e.g. COL1A1, ALP and cbfa1), the immunocytochemical evaluations of osteoblast-related extracellular matrix components (e.g. COL1A1, OCN and ONN) and the ALP activities. All the data suggested that DBM powder could be delivered using a silk fibroin carrier with improved handling characteristics and that 20% DBM/SF scaffolds had great potential as osteogenesis promoting scaffolds for successful applications in bone regeneration.
Co-reporter:Xili Ding;Haifeng Liu
Advanced Healthcare Materials 2015 Volume 4( Issue 10) pp:1451-1468
Publication Date(Web):
DOI:10.1002/adhm.201500203

Graphene possesses many unique properties such as two-dimensional planar structure, super conductivity, chemical and mechanical stability, large surface area, and good biocompatibility. In the past few years, graphene-based materials have risen as a shining star on the path of researchers seeking new materials for future regenerative medicine. Herein, the recent research advances made in graphene-based materials mostly utilizing the mechanical and electrical properties of graphene are described. The most exciting findings addressing the impact of graphene-based materials on regenerative medicine are highlighted, with particular emphasis on their applications including nerve, bone, cartilage, skeletal muscle, cardiac, skin, adipose tissue regeneration, and their effects on the induced pluripotent stem cells. Future perspectives and emerging challenges are also addressed in this Review article.

Co-reporter:Meili Liu;Gang Zhou;Yongzhao Hou;Gang Kuang;Zhengtai Jia;Ping Li
Journal of Biomedical Materials Research Part A 2015 Volume 103( Issue 9) pp:3066-3071
Publication Date(Web):
DOI:10.1002/jbm.a.35426

Abstract

Proper extracellular substrate can stimulate neural regeneration in nerve tissue engineering, including magnetic nanoparticles (iron oxide nanoparticles, Fe3O4), but they are always neurotoxic, with low saturation magnetization and so on. These nanomaterials cannot be used to stimulate the growth and elongation of axons. Therefore, this work attempts to overcome these deficiencies. Nano-hydroxyapatite (n-HA) coated magnetic nanoparticles were using an ultrasound-assisted co-precipitation method. X-ray diffraction and transmission electron microscopy were used to characterize the structure and chemical composition of the produced samples. These synthesized nanomaterials were added into the primary cultured dorsal root ganglion (DRG) neurons; our results showed that n-HA-coated magnetic nanoparticles (Fe3O4+n-HA) can effectively increase cell viability and promote axonal elongation, which enhanced saturation magnetization. In addition, we demonstrated that axonal guidance cues Netrin-1 increase significantly after n-HA-coated magnetic nanoparticles treatment by Western blots assay. n-HA-coated magnetic particles maybe applied to enhance or accelerate nerve regeneration, and it may provide guidance for regenerating axons in future. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3066–3071, 2015.

Co-reporter:Xiaoming Li;Wei Liu;Lianwen Sun;Katerina E. Aifantis;Bo Yu;Qingling Feng;Fuzhai Cui;Fumio Watari
Journal of Biomedical Materials Research Part A 2015 Volume 103( Issue 7) pp:2499-2507
Publication Date(Web):
DOI:10.1002/jbm.a.35384

Abstract

Due to their unique size and properties, nanomaterials have numerous applications, which range from electronics, cosmetics, household appliances, energy storage, and semiconductor devices, to medical products such as biological sensors, drug carriers, bioprobes, and implants. Many of the promising properties of nanomaterials arise from their large surface to volume ratio and, therefore, nanobiomaterials that are implantable have a large contact area with the human body. Before, therefore, we can fully exploit nanomaterials, in medicine and bioengineering; it is necessary to understand how they can affect the human body. As a step in this direction, this review paper provides a comprehensive summary of the effects that the physicochemical properties of commonly used nanobiomaterials have on their toxicity. Furthermore, the possible mechanisms of toxicity are described with the aim to provide guidance concerning the design of the nanobiomaterials with desirable properties. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103: 2499–2507, 2015.

Co-reporter:Haifeng Liu;Xing Wei;Xili Ding;Xiaoming Li;Gang Zhou;Ping Li
Journal of Biomedical Materials Research Part A 2015 Volume 103( Issue 1) pp:115-125
Publication Date(Web):
DOI:10.1002/jbm.a.35154

Abstract

As a brand new member in mesenchymal stem cells (MSCs) families, synovium-derived mesenchymal stem cells (SMSCs) have been increasingly regarded as a promising therapeutic cell species for musculoskeletal regeneration. However, there are few reports mentioning ligamentogenesis of SMSCs and especially null for their engineering use towards ligament regeneration. The aim of this study was to investigate and compare the cellular responses of MSCs derived from bone marrow and synovium on combined silk scaffolds that can be used to determine the cell source most appropriate for tissue-engineered ligament. Rabbit SMSCs and bone marrow-derived mesenchymal stem cells (BMSCs) were isolated and cultured in vitro for two weeks after seeding on the combined silk scaffolds. Samples were studied and compared for their cellular morphology, proliferation, collagen production, gene, and protein expression of ligament-related extracellular matrix (ECM) markers. In addition, the two cell types were transfected with green fluorescent protein to evaluate their fate after implantation in an intraarticular environment of the knee joint. After 14 days of culturing, SMSCs showed a significant increase in proliferation as compared with BMSCs. The transcript and protein expression levels of ligament-related ECM markers in SMSCs were significantly higher than those in BMSCs. Moreover, 6 weeks postoperatively, more viable cells were presented in SMSC-loaded constructs than in BMSC-loaded constructs. Therefore, based on the cellular response in vitro and in vivo, SMSCs may represent a more suitable cell source than BMSCs for further study and development of tissue-engineered ligament. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 115–125, 2015.

Co-reporter:Zhong-Jun Mo;Jun-Chao Guo;Li-zhen Wang;Yu-Bo Fan;Wei Chen
International Orthopaedics 2015 Volume 39( Issue 12) pp:2373-2380
Publication Date(Web):2015/12/01
DOI:10.1007/s00264-015-2889-1
The aim of this study was to evaluate the rationality of the suture locations of distal plantar fascia (DPF) after foot amputation to avoid the risk factors of re-amputation or plantar fasciitis.The tensile strain of plantar fascia (PF) in the different regions was measured by uni-axial tensile experiment. A three-dimensional (3D) finite element model was also developed to simulate tensile behaviour of PF in weight bearing conditions. The model includes 12 bones, ligaments, PF, cartilage and soft tissues. Four suture location models for the DPF were considered: the fourth and fifth DPF were sutured on the third metatarsal, the cuboid, and both the third metatarsal and the cuboid, and one un-sutured model.The peak tensile strain of the first, second and third PF was 0.134, 0.128 and 0.138 based on the mechanical test, respectively. The fourth and fifth DPF sutured at the cuboid and the third metatarsal could offer more favourable outcomes. The peak strain of 4.859 × 10–2, 2.347 × 10–2 and 1.364 × 10–2 in the first, second and third PF showed the least outcomes in stance phase. Also, peak strain and stress of the residual PF reduced to 4.859 × 10–2 and 1.834 MPa, respectively. The stress region was redistributed on the mid-shaft of the first and third PF and the peak stress of medial cuneiform bone evidently decreased.The fourth and fifth DPF suture at the third metatarsal and cuboid was appropriate for the partial foot. The findings are expected to suggest optimal surgical plan of the DPF suture and guide further therapeutic planning of partial foot patients.
Co-reporter:Xiao Yang;Lian-Wen Sun;Meng Liang;Xiao-Nan Wang
Microgravity Science and Technology 2015 Volume 27( Issue 6) pp:473-483
Publication Date(Web):2015 November
DOI:10.1007/s12217-015-9439-8
Osteocytes were considered as potential sensors of mechanical loading and orchestrate the bone remodeling adapted to mechanical loading. On the other hand, osteocytes are also considered as the unloading sensors in vivo. Previous studies showed that the mechanosensation and mechanotransduction of osteocytes may play an essential role in mediating bone response to microgravity, and one of the most important molecular signaling pathway involved in the mechanotransduction is the Wnt/ ß-catenin signaling pathway. In order to investigate the effect of simulated microgravity on the Wnt/ ß-catenin signaling pathway in osteocytes, MLO-Y4 cells (an osteocyte-like cell line) were cultured under controlled rotation to simulate microgravity for 5 days. The cytoskeleton and ß-catenin nuclear translocation of MLO-Y4 cells were detected by laser scanning confocal microscope and the fluorescence intensity was quantified; the mRNA expressions of upstream and downstream key components in Wnt canonical signaling were detected with RT-PCR. Two regulators of the Wnt/ ß-catenin pathway, NMP4/CIZ and Smads, were also investigated by RT-PCR; finally the expression of Wnt target genes and Sost protein level were detected with the absence or presence of the Sclerostin antibody (Scl-AbI) under simulated microgravity. The results showed that under simulated microgravity, (1) F-actin filaments were disassembled and some short dendritic processes appeared at the cell periphery; (2) the gene expression of Wnt3a, Wnt5a, DKK1, CyclinD1, LEF-1 and CX43 in the simulated microgravity group were significantly lower whereas Wnt1 and Sost in the simulated microgravity group were significantly higher than the control group; (3) the gene and protein level of ß-catenin were reduced, and no ß-catenin nuclear translocation observed; (4) the gene expression of Smad1, Smad4 and Smad7 were significantly lower whereas NMP4/CIZ and Smad3 in the simulated microgravity were significantly higher than the control group; (5) Scl-AbI partially inhibited the down-regulation of simulated microgravity to Wnt target gene expression and Sclerostin protein expression. The results suggested that firstly the cytoskeleton was disturbed in MLO-Y4 by simulated microgravity; secondly the activity of Wnt/ ß-catenin signaling pathway was depressed, with the nuclear translocation of ß-catenin suppressed by simulated microgravity; thirdly the Wnt/ ß-catenin signaling pathway positive regulators (Smads) were decreased, while the negative regulator (NMP4/CIZ) was increased under simulated microgravity; finally Scl-AbI could partially restore the adverse effect of simulated microgravity to Wnt signaling. This study may help us to understand the mechanotransduction alteration of Wnt/ ß-catenin signaling pathway in osteocytes under simulated microgravity, and further may partly clarify the mechanism of microgravity-induced osteoporosis.
Co-reporter:Hongyan Kang;Lianwen Sun;Yunfei Huang
Pflügers Archiv - European Journal of Physiology 2015 Volume 467( Issue 6) pp:1291-1301
Publication Date(Web):2015 June
DOI:10.1007/s00424-014-1568-1
Previous animal studies by using tail-suspended hindlimb-unloaded rat model have shown that simulated microgravity-induced vessel structural and functional remodeling may be anatomic region dependent. However, little care has been taken to assess the structural adaptation of the endothelial glycocalyx, the apical surface of the endothelium, the key mechanosensor mediating nitric oxide (NO) production, and the natural protective barrier of the vasculature. Therefore, the present study extended simulated microgravity-induced vessel remodeling to the endothelial glycocalyx level. The percents of bone mineral density (BMD) change from both control and tail-suspended (TS) rats were measured by micro-computed tomography (Micro-CT). Structural parameters such as the luminal diameter (D), the thickness of each layer, the ratio of intima to media (IMR), the cross-sectional areas of the intima (CSAI) and media (CSAM) of vessels from three different regions (the common carotid artery, abdominal aorta, and femoral artery) were assessed by hematoxylin and eosin staining. Dimensions of the glycocalyx above, below, and away from the endothelial cell nucleus were examined by fluorescein isothiocyanate-labeled wheat germ agglutinin (WGA-FITC) binding to the cryosection of vessels. Our results show that 3-week tail suspension of rats increases the thickness and CSA of the abdominal aortic endothelium by 23.7 and 21.1 %, respectively, thickens the media layer of the common carotid artery by 34.0 %, and increases the luminal diameter, the CSA of the intima and media of the femoral artery by 75.7, 93, and 61.2 %, respectively. Correspondingly, the dimension of the glycocalyx away from the common carotid arterial and the abdominal aortic endothelial cell nucleus from tail-suspended rats shows a 1.66- and 1.64-fold increase respectively, while it shows a 0.79-fold reduction on the top of the femoral endothelial cells. These results suggest that simulated microgravity induces vascular endothelial glycocalyx remodeling in a regional-dependent manner. The perturbation of the endothelial glycocalyx at the lower body artery may be the first event of vascular remodeling initiating endothelial dysfunction, contributing to postspaceflight orthostatic intolerance.
Co-reporter:Wen-Xin Niu;Jie Yao;Zhao-Wei Chu
Journal of Medical and Biological Engineering 2015 Volume 35( Issue 1) pp:69-75
Publication Date(Web):2015 February
DOI:10.1007/s40846-015-0007-x
Transient postural stability (TPS) is an individual’s ability to keep postural balance for a short duration. It is particularly useful for evaluating the danger situation faced by persons. This study examines the effects of an inclined surface on TPS during unipedal standing with ankle eversion. Ten male and nine female healthy adults were requested to unipedally stand with dominant and non-dominant leg respectively on a platform. The platform was manually regulated to three inclination angles (0°, 10°, and 20°) for the subjects to stand with ankle eversion. Three ankle stabilizer conditions were investigated, namely barefoot control, elastic ankle tape, and a semi-rigid brace. The plantar pressure distributions were measured and analyzed for 18 conditions (two laterals, three ankle inversions, and three stabilizers) for each subject. The anterior/posterior (A/P-FR) and medial/lateral force rates were used to evaluate TPS in two directions, respectively. The results show that the A/P-FR was significantly higher for the non-dominant side compared with that for the dominant side when subjects stood with ankle eversion, indicating that the anterior/posterior TPS of the non-dominant foot is higher. Ankle eversion mainly destroys the medial/lateral TPS during unipedal standing with the dominant foot. Compared with the semi-rigid ankle brace, the elastic tape was more helpful in maintaining medial/lateral TPS during unipedal standing with ankle eversion.
Co-reporter:Xiao Liu;Min Wang;Nan Zhang;Zhanming Fan
Medical & Biological Engineering & Computing 2015 Volume 53( Issue 5) pp:427-439
Publication Date(Web):2015 May
DOI:10.1007/s11517-015-1250-6
Extrinsic factors such as stent design, deployment and damage to endothelium are associated with stent restenosis and thrombosis. We hypothesize that these extrinsic factors can affect nitric oxide (NO) concentration and disturb its distribution in the stented artery, hence contributing to stent restenosis and thrombosis. We numerically investigated the effects of different endothelium coverage and high-risk factors including thicker strut, stent malapposition and overlapping on the NO distribution in the stented artery. The decrease in the endothelium coverage would greatly reduce the NO concentration, and the location of the coverage relative to the strut significantly affected its distribution. Strut protrusion and thicker strut would induce flow disruption, which not only decreases NO concentration but also greatly changes NO distribution, leading to very low NO concentration near the strut, especially the distal region. Likewise, strut malapposition and overlap would both diminish the NO concentration. However, the distribution of NO for relatively large malapposition was much evener than that for small malapposition. Moreover, proper deployment of the overlapping strut would result in relatively high and uniform NO concentration. In conclusion, less endothelium coverage, thicker struts and improper stent deployment may decrease NO concentration and lead to relatively low NO concentration near the strut.
Co-reporter:Xiao Liu;Anqiang Sun;Xiaoyan Deng
Annals of Biomedical Engineering 2015 Volume 43( Issue 1) pp:3-15
Publication Date(Web):2015 January
DOI:10.1007/s10439-014-1097-2
Helical flow in the human aorta is possibly a typical example of ‘form follows function’ in the vascular system. The helical blood flow may provide guaranties for the inner surface of the ascending aortic wall to get smooth and even washing by the blood so that atherosclerotic plaques can hardly form in the area of the ascending aorta. It has been documented that the phenomenon of helical flow of blood is not just localized in the ascending aorta, it also exists in several large arteries and veins as well. Preliminary studies demonstrated the widely existing helical flow might play positive physiological roles in facilitating blood flow transport, suppressing disturbed blood flow, preventing the accumulation of atherogenic low density lipoproteins on the luminal surfaces of arteries, enhancing oxygen transport from the blood to the arterial wall and reducing the adhesion of blood cells on the arterial surface. These roles of helical blood flow may lessen the burden of arteries and protect the arteries from the pathology of atherosclerosis, thrombosis, and intimal hyperplasia. The great development of time-resolved three-dimensional phase contrast MRI (flow-sensitive 4D-MRI) and the advent of dimensionless indices such as helical flow index proposed to characterize helical flow make clinic quantification of the helical flow in the human large arteries possible. Moreover, researchers probed into the possibility to apply the mechanism of helical flow to the design of vascular interventions to reduce thrombus formation and intimal hyperplasia caused by abnormal flow conditions.
Co-reporter:Xiaoming Li;Yan Huang;Lisha Zheng;Haifeng Liu;Xufeng Niu;Jin Huang;Feng Zhao
Journal of Biomedical Materials Research Part A 2014 Volume 102( Issue 4) pp:1092-1101
Publication Date(Web):
DOI:10.1002/jbm.a.34774

Abstract

Regenerative medicine treatments that combine the use of cells and materials may open new options for tissue/organ repair and regeneration. The microenvironment of mesenchymal stem cells (MSCs) strictly regulates their self-renewal and functions. In this study, when rat bone marrow derived MSCs (rBMSCs) and rat adipose tissue derived MSCs (rAMSCs) in passages 2–4 were cultured on different substrates, they presented the cellular functions to be dependent of substrate stiffness. The cells attached better on the softer substrate than on the stiffer one. The substrate stiffness had no significant influence on the proliferation of those cells. However, the substrate stiffness significantly promoted the osteogenic differentiation of the two kinds of stem cells. Furthermore, rBMSCs cultured on the same stiffness expressed more osteoblast-related markers than rAMSCs. In addition, combined biomaterials and biochemical reagents treatment yielded a stronger effect on osteogenic differentiation of MSCs than either treatment alone. These results have significant implications for further extending our capabilities in engineering functional tissue substitutes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1092–1101, 2014.

Co-reporter:Xiaoming Li;Yu Yang;Qingling Feng;Fu-zhai Cui;Fumio Watari
Journal of Biomedical Materials Research Part A 2014 Volume 102( Issue 5) pp:1580-1594
Publication Date(Web):
DOI:10.1002/jbm.a.34801

Abstract

As a dynamic and hierarchically organized composite, native extracellular matrix (ECM) not only supplies mechanical support, which the embedded cells need, but also regulates various cellular activities through interaction with them. On the basis of the ECM-mimetic principle, good biocompatibility and appropriate mechanical properties are the two basic requirements that the ideal scaffolds for the tissue engineering or regenerative medicine need. Some fibers and tubes have been shown effective to reinforce scaffolds for tissue engineering or regenerative medicine. In this review, three parts, namely properties affected by the addition of fibers or tubes, scaffolds reinforced by fibers or tubes for soft tissue repair, and scaffolds reinforced by fibers or tubes for hard tissue repair are stated, which shows that tissue repair or regeneration efficacy was enhanced significantly by fiber or tube reinforcement. In addition, it indicates that these reinforcing agents can improve the biocompatibility and biodegradation of the scaffolds in most cases. However, there are still some concerns, such as the homogeneousness in structure or composition throughout the reinforced scaffolds, the adhesive strength between the matrix and the fibers or tubes, cytotoxicity of nanoscaled reinforcing agents, etc., which were also discussed in the conclusion and perspectives part. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1580–1594, 2014.

Co-reporter:Jin Huang, Ping Dong, Weichang Hao, Tianmin Wang, Yayi Xia, Guozu Da, Yubo Fan
Applied Surface Science 2014 Volume 313() pp:172-182
Publication Date(Web):15 September 2014
DOI:10.1016/j.apsusc.2014.05.182

Abstract

NiTi shape memory alloy has been used widely as implanted material; however, possible release of Ni ions may cause toxic, allergic, and potentially carcinogenic effects in a physiological environment. In order to solve this problem, we notice that, as shown by previous studies, anticoagulant heparin is a better material for improving blood biocompatibility. Thus a promising way is to develop new TiO2/heparin coatings on NiTi shape memory alloy, for the purpose of reducing possible release of toxic Ni ions and hence improve hemocompatibility. In this regard, we have fabricated four kinds of hemocompatible coatings: sol–gel TiO2, heating TiO2, sol–gel TiO2/heparin and heating TiO2/heparin on NiTi shape memory alloy. Various measurements have been done against this new material, including FE-SEM, XRD and contact angle tests (used to monitor surface characters), as well as hemolytic tests, dynamic clotting time experiments, platelet binding tests, cell morphology, MTT, ALP and RT-PCR (utilized to investigate blood- and cell-compatibility). Our results reveal that this new material of heparin loaded coatings, as expected, is able to improve the hemocompatibility of NiTi surgical alloy material. Moreover, RT–PCR measurements indicate that the best coating for cell growth is the heating TiO2/heparin. Our results suggest that deposition of TiO2 and heparin coating on the surface of a NiTi alloy sample is a promising method to improve its hemocompatibility.

Co-reporter:Gang Zhou;Wei Song;Yongzhao Hou;Qing Li;Xuliang Deng
Journal of Biomedical Materials Research Part A 2014 Volume 102( Issue 10) pp:3704-3712
Publication Date(Web):
DOI:10.1002/jbm.a.35043

Abstract

This work describes the fabrication and characterization of a biocompatible magnetic hydroxyapatite (HA) using an ultrasound-assisted co-precipitation method. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM) were used to characterize the structure and chemical composition of the produced samples. The M–H loops of synthesized materials were traced using a vibrating sample magnetometer (VSM) and the biocompatibility was evaluated by cell culture and MTT (3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide) assay. Furthermore, in vivo histopathological examinations were used to evaluate the potential toxicological effects of Fe3O4-HA composites on kidney of SD rats injected intraperitoneally with Fe3O4-HA particles. The results showed that magnetic iron oxide particles first replace OH ions of HA, which are parallel to the c axis, and then enter the HA crystal lattice which produces changes in the crystal surface of HA. Chemical bond interaction was observed between PO43− groups of HA and iron ions of Fe3O4. The saturation magnetization (MS) of Fe3O4-HA composites was 46.36 emu/g obtained from VSM data. Cell culture and MTT assays indicated that HA could affect the growth and proliferation of HEK-293 cells. This Fe3O4-HA composite produced no negative effects on cell morphology, viability, and proliferation and exhibited remarkable biocompatibility. Moreover, no inflammatory cell infiltration was observed in kidney histopathology slices. Therefore, this study succeeds to develop a Fe3O4-HA composite as a prospective biomagnetic material for future applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3704–3712, 2014.

Co-reporter:Ping Li, Yanhui Song, Chengguo Liu, Xiaoming Li, Gang Zhou, Yubo Fan
Materials Letters 2014 Volume 114() pp:132-135
Publication Date(Web):1 January 2014
DOI:10.1016/j.matlet.2013.09.111
•The fluorescent-labeling drug Gd(aspirin)3·2H2O was prepared by covalent binding of rare earth ion Gd3+ with aspirin.•Fe3O4 and Gd(aspirin)3·2H2O were incorporated into chitosan microspheres to obtain the bifunctional drug delivery system (DDS).•The prepared DDS showed good fluorescent and magnetic properties.•With the fluorescent-labeling drug, we can study the drug release exactly due to the binding of fluorescent mark and drug.The fluorescent marker in the drug delivery system (DDS) is very critical to achieve dynamic tracing of drug. However, the DDS embedded with fluorescent materials is not capable of detecting the release of drug precisely, since the separated fluorescent substrate and drug do not release and diffuse simultaneously. To increase the accuracy of tracing drug, we prepared fluorescent-labeling drug Gd(aspirin)3·2H2O by covalent binding of rare earth ion Gd3+ with aspirin. Fe3O4 magnetic nanoparticles as the magnetic targeting carrier and Gd(aspirin)3·2H2O as the fluorescent-labeling drug were incorporated into chitosan microspheres to prepare magnetic and fluorescent chitosan microspheres as a DDS. Investigated by Fourier transform infrared spectrometer, Varioskan Flash, X-ray diffraction, vibrating sample magnetometer, transmission electron microscope, and scanning electron microscope, the DDS with fluorescent-labeling drug showed good fluorescent and magnetic properties.
Co-reporter:Xianghui Gong, Haifeng Liu, Xili Ding, Meili Liu, Xiaoming Li, Lisha Zheng, Xiaoling Jia, Gang Zhou, Yuanwen Zou, Jinchuan Li, Xuejin Huang, Yubo Fan
Biomaterials 2014 35(17) pp: 4782-4791
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.02.050
Co-reporter:Chunhoi Yan;Yubo Fan;Jason Tak-Man Cheung;Ming Zhang;Chun Yi Wen;Kwong-Yuen Chiu;Jie Yao;William Weijia Lu
International Orthopaedics 2014 Volume 38( Issue 5) pp:973-981
Publication Date(Web):2014/05/01
DOI:10.1007/s00264-014-2290-5
The tibial drill-guide angle in anterior cruciate ligament (ACL) reconstruction influences the tunnel placement and graft-tunnel force, and is potentially associated with post-operative tunnel widening. This study aimed to examine the effect of the drill-guide angle on the stress redistribution at the tibial tunnel aperture after anatomic single-bundle ACL reconstruction.A validated finite element model of human knee joint was used. The tibial tunnel with drill-guide angle ranging from 30° to 75° was investigated. The post-operative stress redistribution in tibia under the compressive, valgus, rotational and complex loadings was analysed.Compressive loading played a leading role on the stress redistribution at intra-articular tibial tunnel aperture. After ACL reconstruction, stress concentration occurred in the anterior and posterior regions of tunnel aperture while stress reduction occurred in the lateral and posteromedial regions under the compressive loading. Stress redistribution was partially alleviated by using the drill-guide angle ranging from 55° to 65°.The present study quantified the effect of bone tunnel drill-guide angle on the post-operative stress redistribution. This phenomenon potentially contributed to tunnel widening. A tunnel drill-guide angle ranging from 55° to 65° was proposed based on the biomechanical rationale. It could serve as a helpful surgical guide for ACL reconstruction.
Co-reporter:Yan Bin Zhao;Zhong Jun Mo;Li Zhen Wang;Yu Sun;Ming Zhang;Yu Bo Fan
European Spine Journal 2014 Volume 23( Issue 3) pp:
Publication Date(Web):2014/03/01
DOI:10.1007/s00586-013-3070-4
Various design concepts have been adopted in cervical disc prostheses, including sliding articulation and standalone configuration. This study aimed to evaluate the biomechanical effects of the standalone U-shaped configuration on the cervical spine.Based on an intact finite element model of C3–C7, a standalone U-shaped implant (DCI) was installed at C5–C6 and compared with a sliding articulation design (Prodisc-C) and an anterior fusion system. The range of motion (ROM), adjacent intradiscal pressure (IDP) and capsular ligament strain were calculated under different spinal motions.Compared to the intact configuration, the ROM at C5–C6 was reduced by 90 % after fusion, but increased by 70 % in the Prodisc-C model, while the maximum percentage change in the DCI model was 30 % decrease. At the adjacent segments, up to 32 % increase in ROM happened after fusion, while up to 34 % decrease occurred in Prodisc-C model and 17 % decrease in DCI model. The IDP increased by 11.6 % after fusion, but decreased by 5.6 and 6.3 % in the DCI and Prodisc-C model, respectively. The capsular ligament strain increased by 147 % in Prodisc-C and by 13 % in the DCI model. The DCI implant exhibited a high stress distribution.Spinal fusion resulted in compensatory increase of ROM at the adjacent sites, thereby elevating the IDP. Prodisc-C resulted in hyper-mobility at the operative site that led to an increase of ligament force and strain. The U-shaped implant could maintain the spinal kinematics and impose minimum influence on the adjacent soft tissues, despite the standalone configuration encountering the disadvantages of high stress distribution.
Co-reporter:Xu-feng Niu 牛旭锋;Feng Tian;Li-zhen Wang
Chinese Journal of Polymer Science 2014 Volume 32( Issue 1) pp:43-50
Publication Date(Web):2014 January
DOI:10.1007/s10118-014-1369-1
Chitosan-graft-poly(lactic acid) (CS-g-PLA) copolymer was synthesized through emulsion self-assembly in a water-in-oil (W/O) microemulsion. The water phase was composed of CS aqueous solution, while the oil phase was made up of PLA in chloroform. The W/O microemulsion was fabricated in the presence of surfactant span-80 and the self-assembly was performed between PLA and CS under the effect of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC·HCl). FTIR and 1H-NMR analysis indicated PLA was grafted onto the backbone of CS via the reaction between the carboxyl groups in PLA and the amino groups in CS. 1H-NMR characterization further revealed the grafting content of PLA was 16%. The obtained CS-g-PLA could self-assemble to form micelles, their size distributed in the range of 125–375 nm with average diameter of 142 nm. The present design integrates the favorable biological properties of CS and the excellent mechanical properties of PLA, which makes CS-g-PLA copolymer a promising candidate as a carrier for targeted bioactive molecules delivery.
Co-reporter:JingYun Han;JianXia Hou;Gang Zhou;Chao Wang
Science China Life Sciences 2014 Volume 57( Issue 6) pp:618-626
Publication Date(Web):2014 June
DOI:10.1007/s11427-014-4657-7
Immediate loading (IL) increases the risk of marginal bone loss. The present study investigated the biomechanical response of peri-implant bone in rabbits after IL, aiming at optimizing load management. Ninety-six implants were installed bilaterally into femurs of 48 rabbits. Test implants on the left side created the maximal initial stress of 6.9 and 13.4 MPa in peri-implant bone and unloaded implants on the contralateral side were controls. Bone morphology and bone-implant interface strength were measured with histological examination and push-out testing during a 12-week observation period. Additionally, the animal data were incorporated into finite element (FE) models to calculate the bone stress distribution at different levels of osseointegration. Results showed that the stress was concentrated in the bone margin and the bone stress gradually decreased as osseointegration proceeded. A stress of about 2.0 MPa in peri-implant bone had a positive effect on new bone formation, osseointegration and bone-implant interface strength. Bone loss was observed in some specimens with stress exceeding 4.0 MPa. Data indicate that IL significantly increases bone stress during the early postoperative period, but the load-bearing capacity of peri-implant bone increases rapidly with an increase of bone-implant contact. Favorable bone responses may be continually promoted when the stress in peri-implant bone is maintained at a definite level. Accordingly, the progressive loading mode is recommended for IL implants.
Co-reporter:WenXin Niu;TingTing Tang;Ming Zhang;ChengHua Jiang
Science China Life Sciences 2014 Volume 57( Issue 12) pp:1191-1196
Publication Date(Web):2014 December
DOI:10.1007/s11427-014-4731-1
A good knowledge of midfoot biomechanics is important in understanding the biomechanics of the entire foot, but it has never been investigated thoroughly in the literature. This study carried out in vitro experiments and finite element analysis to investigate the midfoot biomechanics. A foot-ankle finite element model simulating the mid-stance phase of the normal gait was developed and the model validated in in vitro experimental tests. Experiments used seven in vitro samples of fresh human cadavers. The simulation found that the first principal stress peaks of all midfoot bones occurred at the navicular bone and that the tensile force of the spring ligament was greater than that of any other ligament. The experiments showed that the longitudinal strain acting on the medial cuneiform bone was −26.2±10.8 μ-strain, and the navicular strain was −240.0±169.1 μ-strain along the longitudinal direction and 65.1±25.8 μ-strain along the transverse direction. The anatomical position and the spring ligament both result in higher shear stress in the navicular bone. The load from the ankle joint to five branches of the forefoot is redistributed among the cuneiforms and cuboid bones. Further studies on the mechanism of loading redistribution will be helpful in understanding the biomechanics of the entire foot.
Co-reporter:Zhiwei Jia;Zhongjun Mo;Fan Ding;Qing He;Yubo Fan;Dike Ruan
European Spine Journal 2014 Volume 23( Issue 8) pp:
Publication Date(Web):2014/08/01
DOI:10.1007/s00586-014-3389-5
The optimal surgical technique for multilevel cervical degenerative disc diseases (DDD) remains controversial. Hybrid surgery (HS) incorporating anterior cervical discectomy and fusion (ACDF) and cervical disc replacement (CDR) is increasingly performed for cervical DDD. This study aims to evaluate the biomechanical and clinical evidence available for HS and to provide a systematic review of current understanding of HS.This systematic review was undertaken by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Multiple databases and online registers of clinical trials were searched up to February 2014. The biomechanical and clinical studies on HS for cervical DDD written in English were included. Two authors independently assessed methodological quality and extracted data.Fifteen studies including eight biomechanical studies and seven clinical studies were indentified. The biomechanical studies showed that HS was benefit to motion preservation of the operative levels and revealed less adverse effect on adjacent segments. All clinical studies demonstrated improvement in validated functional scores after HS. Segment motion and immobilization were achieved at the arthroplasty level and arthrodesis level, respectively. Postoperative assessments and complication rate were similar or in favor of HS when comparing with ACDF or CDR. However, the overall quality of evidence for HS was low to very low.There is a paucity of high quality evidence for HS. HS may be a safe and efficacious technique to benefit a select group of multilevel cervical DDD, which is needed to be confirmed by further prospective, randomized controlled trials.
Co-reporter:Jie Yao;Guan-Ming Kuang;Duo Wai-Chi Wong;Wen-Xin Niu
Acta Mechanica Sinica 2014 Volume 30( Issue 2) pp:241-249
Publication Date(Web):2014 April
DOI:10.1007/s10409-014-0027-8
Postoperative tunnel enlargement has been frequently reported after anterior cruciate ligament (ACL) reconstruction. Interference screw, as a surgical implant in ACL reconstruction, may influence natural loading transmission and contribute to tunnel enlargement. The aims of this study are (1) to quantify the alteration of strain energy den sity (SED) distribution after the anatomic single-bundle ACL reconstruction; and (2) to characterize the influence of screw length and diameter on the degree of the SED alteration. A validated finite element model of human knee joint was used. The screw length ranging from 20 to 30mm with screw diameter ranging from 7 to 9 mm were investigated. In the post-operative knee, the SED increased steeply at the extra-articular tunnel aperture under compressive and complex loadings, whereas the SED decreased beneath the screw shaft and nearby the intra-articular tunnel aperture. Increasing the screw length could lower the SED deprivation in the proximal part of the bone tunnel; whereas increasing either screw length or diameter could aggravate the SED deprivation in the distal part of the bone tunnel. Decreasing the elastic modulus of the screw could lower the bone SED deprivation around the screw. In consideration of both graft stability and SED alteration, a biodegradable interference screw with a long length is recommended, which could provide a beneficial mechanical environment at the distal part of the tunnel, and meanwhile decrease the bone-graft motion and synovial fluid propagation at the proximal part of the tunnel. These findings together with the clinical and histological factors could help to improve surgical outcome, and serve as a preliminary knowledge for the following study of biodegradable interference screw.
Co-reporter:Haifeng Liu;Xili Ding;Yanxue Bi;Xianghui Gong;Xiaoming Li;Gang Zhou
Macromolecular Bioscience 2013 Volume 13( Issue 6) pp:755-766
Publication Date(Web):
DOI:10.1002/mabi.201200470
Co-reporter:Xiaoming Li;Lu Wang;Qingling Feng;Fu-Zhai Cui;Fumio Watari
Journal of Biomedical Materials Research Part A 2013 Volume 101A( Issue 8) pp:2424-2435
Publication Date(Web):
DOI:10.1002/jbm.a.34539

Abstract

It has been demonstrated that nanostructured materials, compared with conventional materials, may promote greater amounts of specific protein interactions, thereby more efficiently stimulating new bone formation. It has also been indicated that, when features or ingredients of scaffolds are nanoscaled, a variety of interactions can be stimulated at the cellular level. Some of those interactions induce favorable cellular functions while others may leads to toxicity. This review presents the mechanism of interactions between nanoscaled materials and cells and focuses on the current research status of nanostructured scaffolds for bone tissue engineering. Firstly, the main requirements for bone tissue engineering scaffolds were discussed. Then, the mechanism by which nanoscaled materials promote new bone formation was explained, following which the current research status of main types of nanostructured scaffolds for bone tissue engineering was reviewed and discussed. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

Co-reporter:Xufeng Niu;Lizhen Wang;Pin Chen;Xiaoming Li;Gang Zhou;Qingling Feng
Macromolecular Chemistry and Physics 2013 Volume 214( Issue 6) pp:700-706
Publication Date(Web):
DOI:10.1002/macp.201200597

Abstract

An amphiphilic graft copolymer using chitosan (CS) as a hydrophilic main chain and poly(lactic-co-glycolic acid) (PLGA) as a hydrophobic side chain is prepared through an emulsion self-assembly synthesis. CS aqueous solution is used as a water phase and PLGA in chloroform is served as an oil phase. A water-in-oil (W/O) emulsion is fabricated in the presence of the surfactant span-80. The self-assembly reaction is performed between PLGA and CS under the condensation of EDC. Fourier transform IR (FTIR) spectroscopy reveals that PLGA is grafted onto the backbone of CS through the interactions between end carboxyl and amino groups of the two components. 1H NMR spectroscopy directly indicates the grafting content of PLGA in the CS-graft-PLGA (CS-g-PLGA) copolymer is close to 25%. X-ray diffraction (XRD) confirms that the copolymer exhibits an amorphous structure. The CS-g-PLGA amphiphile can self-assemble to form micelles with size in the range of ≈100–300 nm, which makes it easy to apply in various targeted-drug-release and biomaterial fields.

Co-reporter:Fengxuan Han, Xiaoling Jia, Dongdong Dai, Xiaoling Yang, Jin Zhao, Yunhui Zhao, Yubo Fan, Xiaoyan Yuan
Biomaterials 2013 34(30) pp: 7302-7313
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.06.006
Co-reporter:Hong Zhang, Xiaoling Jia, Fengxuan Han, Jin Zhao, Yunhui Zhao, Yubo Fan, Xiaoyan Yuan
Biomaterials 2013 34(9) pp: 2202-2212
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.12.005
Co-reporter:Chi Zhang;Fang Pu;Shuyu Li;Sheng Xie
Surgical and Radiologic Anatomy 2013 Volume 35( Issue 5) pp:
Publication Date(Web):2013/07/01
DOI:10.1007/s00276-012-1042-8
The development of intracranial internal carotid artery (ICA) stenoses may be associated with the morphology of the siphon. The aim is to quantitatively characterize the geometry of ICA, and develop a classifier of the ICA shape in relation to the location and incidence of stenoses.The ICA geometry from 74 subjects was analyzed by means of image-based computational techniques. The siphon was split into two bends, and was described in terms of curvature radius, radius of vessel, angle of bending, and length. Differences of geometry between ICA classes were assessed in control group, consisted of 30 subjects without stenoses. In stenosed group, the association between the ICA classes and the incidence of stenoses were investigated and validated by hemodynamic simulation.The curvature radius and angle of the posterior bend were significantly different between ICA classes, as well as the angle between the two bends. An innovative classifier was developed with the three geometric parameters. The ICA classification was found associated with the incidence of stenoses at the siphon.Geometric factors relative to the ICA were correlated with the location and incidence of stenoses at the siphon. The present work has potential implications in the quest for hemodynamic factors contributing to the initiation and progression of intracranial ICA stenoses.
Co-reporter:Xiaoling Jia;Jingyun Yang;Wei Song
Pflügers Archiv - European Journal of Physiology 2013 Volume 465( Issue 2) pp:221-232
Publication Date(Web):2013 February
DOI:10.1007/s00424-012-1182-z
The large conductance Ca2+-activated K+ (BKCa) channel in vascular smooth muscle cell (VSMC) is an important potassium channel that can regulate vascular tone. Recent work has demonstrated that abnormalities in BKCa channel function are associated with changes in cell proliferation and the onset of vascular disease. However, until today there are rare reports to show whether this channel is involved in VSMC proliferation in response to fluid shear stress (SS). Here we investigated a possible role of BKCa channel in VSMC proliferation under laminar SS. Rat aortic VSMCs were plated in parallel-plate flow chambers and exposed to laminar SS with varied durations and magnitudes. VSMC proliferation was assessed by measuring proliferating cell nuclear antigen (PCNA) expression and DNA synthesis. BKCa protein and gene expression was determined by flow cytometery and RT-PCR. The involvement of BKCa in SS-induced inhibition of proliferation was examined by BKCa inhibition using a BKCa specific blocker, iberiotoxin (IBTX), and by BKCa transfection in BKCa non-expressing CHO cells. The changes in [Ca2+]i were determined using a calcium-sensitive dye, fluo 3-AM. Membrane potential changes were detected with a potential-sensitive dye, DiBAC4(3). We found that laminar SS inhibited VSMC proliferation and stimulated BKCa channel expression. Furthermore, laminar SS induced an increase in [Ca2+]i and membrane hyperpolarization. Besides in VSMC, the inhibitory effect of BKCa channel activity on cell proliferation in response to SS was also confirmed in BKCa-transfected CHO cells showing a decline in proliferation. Blocking BKCa channel reversed its inhibitory effect, providing additional support for the involvement of BKCa in SS-induced proliferation reduction. Our results suggest, for the first time, that BKCa channel mediates laminar SS-induced inhibition of VSMC proliferation. This finding is important for understanding the mechanism by which SS regulates VSMC proliferation, and should be helpful in developing strategies to prevent flow-initiated vascular disease formation.
Co-reporter:LiZhen Wang;Shan Lu;XiaoYu Liu;XuFeng Niu;Chao Wang
Science China Life Sciences 2013 Volume 56( Issue 8) pp:715-719
Publication Date(Web):2013 August
DOI:10.1007/s11427-013-4523-z
The woodpecker does not suffer head/eye impact injuries while drumming on a tree trunk with high acceleration (more than 1000×g) and high frequency. The mechanism that protects the woodpecker’s head has aroused the interest of ornithologists, biologists and scientists in the areas of mechanical engineering, material science and electronics engineering. This article reviews the literature on the biomechanisms and materials responsible for protecting the woodpecker from head impact injury and their applications in engineering and human protection.
Co-reporter:Liting Wang, Gang Zhou, Haifeng Liu, Xufeng Niu, Jingyun Han, Lisha Zheng and Yubo Fan  
Nanoscale 2012 vol. 4(Issue 9) pp:2894-2899
Publication Date(Web):07 Mar 2012
DOI:10.1039/C2NR00044J
While the advantages of nanomaterials are being increasingly recognized, their potential toxicity is drawing more and more attention and concern. In this study, we explore the toxicity mechanism of 20–30 nm rod-shaped hydroxyapatite (HA) nanoparticles in vitro and in vivo. The nanoparticles were prepared by precipitation and characterized by IR, XRD and TEM. Concentrations of 0 μg mL−1, 10 μg mL−1, 100 μg mL−1, 1 mg mL−1, and 10 mg mL−1 were applied to the MC3T3-E1 cells for viability (MTT-test). Based on the characteristic differences of the two methods of cell death, the morphological features of the MC3T3-E1 cell line co-cultured with nano-hydroxyapatite (n-HA) (10 mg mL−1) for 24 h were also observed by TEM. Furthermore, important serum biochemical markers and histopathological examinations were used to evaluate the potential toxicological effect of n-HA on the major organs of SD rats injected intraperitoneally with n-HA (33.3 mg kg−1 body weight). In the results, we found cell growth inhibition and apoptosis in MC3T3-E1 cells co-cultured with n-HA. Moreover, apoptosis but not necrosis was illustrated in liver and renal tissue by using histopathology slices and serum biochemical markers. It suggests that apoptosis may be the possible mechanism of n-HA toxicity and provides a better understanding of the biocompatibility of nanomaterials applied in human bone repair.
Co-reporter:Gang Zhou, Yongzhao Hou, Lei Liu, Hongru Liu, Can Liu, Jing Liu, Huiting Qiao, Wenyong Liu, Yubo Fan, Shituan Shen and Long Rong  
Nanoscale 2012 vol. 4(Issue 24) pp:7698-7703
Publication Date(Web):06 Sep 2012
DOI:10.1039/C2NR31486J
The synthesis, characterization and catalytic capability of the NiW–nano-hydroxyapatite (NiW–nHA) composite were investigated in this paper. The NiW–nHA catalyst was prepared by a co-precipitation method. Then Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD) and energy dispersive spectroscopy (EDX) were used to analyze this material. In addition, the catalytic capacity of the NiW–nHA composite was also examined by FT-IR and gas chromatography (GC). The results of FT-IR analysis indicated that Ni, W and nHA combined closely. TEM observation revealed that this catalyst was needle shaped and the crystal retained a nanometer size. XRD data also suggested that a new phase of CaWO4 appeared and the lattice parameters of nHA changed in this system. nHA was the carrier of metals. The rates of Ni/W-loading were 73.24% and 65.99% according to the EDX data, respectively. Furthermore, the conversion of 91.88% Jatropha oil was achieved at 360 °C and 3 MPa h−1 over NiW–nHA catalyst. The straight chain alkanes ranging from C15 to C18 were the main components in the production. The yield of C15–C18 alkanes was up to 83.56 wt%. The reaction pathway involved hydrocracking of the CC bonds of these triglycerides from Jatropha oil. This paper developed a novel non-sulfided catalyst to obtain a “green biofuel” from vegetable oil.
Co-reporter:Meili Liu, Gang Zhou, Wei Song, Ping Li, Haifeng Liu, Xufeng Niu and Yubo Fan  
Nanoscale 2012 vol. 4(Issue 10) pp:3201-3207
Publication Date(Web):21 Mar 2012
DOI:10.1039/C2NR30072A
Nanomaterials such as carbon nanotubes (CNT) can improve axonal connecting in a target direction during regeneration, however, it is limited by the neurotoxicity of CNT. Here we investigate the possible protective effect of nano-hydroxyapatite (n-HA) against nerve injury, as well as CNT in cultured rat cortical neurons. In this study the nanomaterials were characterized by X-Ray diffractometry (XRD) and atomic force microscopy (AFM) analysis. Our results showed that axonal migration and extension were increased significantly after n-HA treatment by immunocytochemistry assay. The patch clamp assay results showed that n-HA acts protectively after nerve injury, which inhibited the average amplitude and frequency of excitatory postsynaptic currents (EPSCs). n-HA is not neurotoxic for the electrophysiology activity of cells. To find the effect of n-HA on axonal guidance growth in the cultured cortical neurons, Netrin 1, one of the axonal guidance cues, was determined by RT-PCR and western blot assay. Compared to the control group, n-HA down-regulated the mRNA level of netrin 1, and moreover, the expression of netrin 1 decreased significantly in the cells. n-HA caused the axonal guidance growth to be mediated by netrin 1 during nerve regeneration. Therefore, the data from the present study provided a new approach for the therapy or prevention of nerve injury.
Co-reporter:Yan Huang, Gang Zhou, Lisha Zheng, Haifeng Liu, Xufeng Niu and Yubo Fan  
Nanoscale 2012 vol. 4(Issue 7) pp:2484-2490
Publication Date(Web):15 Feb 2012
DOI:10.1039/C2NR12072K
Regenerative medicine consisting of cells and materials provides a new way for the repair and regeneration of tissues and organs. Nano-biomaterials are highlighted due to their advantageous features compared with conventional micro-materials. The aim of this study is to investigate the effects of micro-/nano- sized hydroxyapatite (μ/n-HA) on the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). μ/n-HA were prepared by a microwave synthesizer and precipitation method, respectively. Different sizes of μ/n-HA were characterized by IR, XRD, SEM, TEM and co-cultured with rBMSCs. It was shown that rBMSCs expressed higher levels of osteoblast-related markers by n-HA than μ-HA stimulation. The size of HA is an important factor for affecting the osteogenic differentiation of rBMSCs. This provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated cells.
Co-reporter:HaiJun Niu;LiFeng Li;Kai Liao;XiaoGuang Li
Science Bulletin 2012 Volume 57( Issue 18) pp:2280-2284
Publication Date(Web):2012 June
DOI:10.1007/s11434-012-5219-7
Many studies have shown that strategies of nerve regeneration and cell-based transplantation are valid based on animal models of spinal cord injury (SCI). To apply these strategies and bridge spinal cord defects, the identification and precise localization of lesions during spinal cord surgery is necessary. The aim of the present experiment was to evaluate the capabilities of ultrasound backscatter microscopy (UBM) in identifying morphologic changes after SCI. After laminectomy, high-resolution ultrasound images of the spinal cord were obtained in one normal and seven spinal cord-injured adult Wistar rats using a UBM system with a 55-MHz center frequency scanner. Comparison between histoanatomic and UBM images was also performed. The results showed that UBM can identify cysts after the experimental SCI is removed in adult rats. In addition, the glial scar formed in secondary injury showed obvious hyperechoic speckle in the UBM image and correlated with the histoanatomic image. UBM has obvious clinical value in nerve regeneration and cell-based transplantation strategies in injured spinal cords.
Co-reporter:HaiJun Niu;ChengRui Liu;Ang Li;Qing Wang;YueXiang Wang
Science China Life Sciences 2012 Volume 55( Issue 5) pp:444-451
Publication Date(Web):2012/05/01
DOI:10.1007/s11427-012-4326-7
The purpose of this study was to explore the triphasic mechanical properties of osteoarthritic cartilage with different pathological grades. First, samples of cartilage from rabbits with different stages of osteoarthritis (OA) were graded. Following this, the cartilage was strained by a swelling experiment, and changes were measured using a high-frequency ultrasound system. The result, together with fixed charge density and water volume fraction of cartilage samples, was used to estimate the uniaxial modulus of the cartilage tissue, based on a triphasic model. For the control cartilage samples, the uniaxial elastic modulus on the cartilage surface was lower than those in the middle and deep layers. With an increase in the OA grade, the uniaxial elastic modulus of the surface, middle and deep layers decreased. A significant difference was found in the surface elastic modulus of different OA grades (P<0.01), while no significant differences were identified for OA cartilages of Grades 1 and 2 in the middle and deep layers (P<0.01). Compared with Grades 1 and 2, there was a significant reduction in the elastic modulus in the middle and deep layers of Grade 3 OA cartilage (P<0.05). Overall, this study may provide a new quantitative method to evaluate the severity of OA using the mechanical properties of cartilage tissue.
Co-reporter:Xiaoming Li, Haifeng Liu, Xufeng Niu, Bo Yu, Yubo Fan, Qingling Feng, Fu-zhai Cui, Fumio Watari
Biomaterials 2012 Volume 33(Issue 19) pp:4818-4827
Publication Date(Web):June 2012
DOI:10.1016/j.biomaterials.2012.03.045
Carbon nanotubes (CNTs), one of the most concerned nanomaterials, with unique electrical, mechanical and surface properties, have been shown suitable for biomedical application. In this study, we evaluated attachment, proliferation, osteogenic gene expression, ALP/DNA, protein/DNA and mineralization of human adipose-derived stem cells cultured in vitro on multi-walled carbon nanotubes (MWNTs) and graphite (GP) compacts with the same dimension. Moreover, we assessed the effect of these two kinds of compacts on ectopic bone formation in vivo. First of all, higher ability of the MWNTs compacts to adsorb proteins, comparing with the GP compacts, was shown. During the conventional culture, it was shown that MWNTs could induce the expression of ALP, cbfa1 and COLIA1 genes while GP could not. Furthermore, alkaline phosphatase (ALP)/DNA and protein/DNA of the cell on the MWNTs compacts, was significantly higher than those of the cells on the GP compacts. With the adsorption of the proteins in culture medium with 50% fetal bovine serum (FBS) in advance, the increments of the ALP/DNA and protein/DNA for the MWNTs compacts were found respectively significantly more than the increments of those for the GP compacts, suggesting that the larger amount of protein adsorbed on the MWNTs was crucial. More results showed that ALP/DNA and protein/DNA of the cells on the two kinds of compacts pre-soaked in culture medium having additional rhBMP-2 were both higher than those of the cells on the samples re-soaked in culture medium with 50% FBS, and that those values for the MWNTs compacts increased much more. Larger mineral content was found on the MWNTs compacts than on the GP compacts at day 7. In vivo experiment showed that the MWNTs could induce ectopic bone formation in the dorsal musculature of ddy mice while GP could not. The results indicated that MWNTs might stimulate inducible cells in soft tissues to form inductive bone by concentrating more proteins, including bone-inducing proteins.
Co-reporter:Jie Yao;ChunYi Wen;Jason Tak-Man Cheung;Ming Zhang
Annals of Biomedical Engineering 2012 Volume 40( Issue 7) pp:1554-1567
Publication Date(Web):2012 July
DOI:10.1007/s10439-012-0517-4
Bone tunnel enlargement is a common effect associated with knee laxity after anterior cruciate ligament (ACL) reconstruction. Nevertheless, its exact pathomechanism remains controversial. One of the possible reasons could be bone remodeling due to tunnel creation, which changes the stress environment in the joint. The present study aims to characterize the deteriorated stress distribution on the articular surface, which is due to tunnel creation after single-bundle or double-bundle ACL reconstruction. The stress distributions in the knee following ACL reconstruction under the compression, rotation, and valgus torques were calculated using a validated three-dimensional finite element (FE) model. The results indicate that, (a) under compression, von Mises stress is decreased at lateral and posteromedial regions of single/anteromedial (AM) tunnel, whereas it is increased at anterior region of single/AM tunnel in tibial subchondral bone; (b) the concentration of tensile stress is transferred from the articular surface to the location of graft fixation, and tensile stress in subchondral plate is decreased after ACL reconstruction; (c) severe stress concentration occurs between AM and posterolateral tunnels following the double-bundle reconstruction, which may contribute to the tunnel communication after surgery. In summary, the present study affirms that the deterioration of stress distribution occurs near the articular surface, which may cause the collapse of the tunnel wall, and lead to tunnel enlargement. The present study provides an insight into the effect of tunnel creation on articular stress deterioration after single-bundle or double-bundle ACL reconstruction. These findings provide knowledge on the effect of tunnel enlargement after ACL reconstruction in the long term.
Co-reporter:Lian Wen Sun;Chao Wang;Fang Pu;De Yu Li;Hai Jun Niu
Calcified Tissue International 2011 Volume 88( Issue 1) pp:48-53
Publication Date(Web):2011 January
DOI:10.1007/s00223-010-9422-8
Depending on the experimental design, micro-CT can be used to examine bones either in vivo or ex vivo (excised fresh or formalin-fixed). In this study we investigated if differences exist in the variables measured by micro-CT between in vivo and ex vivo scans and which kind of scan is more sensitive to the changes of bone microstructure induced by simulated weightlessness. Rat tail suspension was used to simulate the weightless condition. The same bone from either normal or tail-suspended rats was scanned by micro-CT both in vivo and ex vivo (fresh and fixed by formalin). Then, bone mineral density (BMD) and microstructural characteristics were analyzed. The results showed that no significant differences existed in the microstructural parameters of trabecular bone among in vivo, fresh, and formalin-fixed bone scans from both femurs and tibias, although BMD exhibited differences. On the other hand, most parameters of the tail-suspended rats measured by micro-CT deteriorated compared with controls. Ex vivo scanning appeared to be more sensitive to bone microstructural changes induced by tail suspension than in vivo scanning. In general, the results indicate that values obtained in vivo and ex vivo (fresh and fixed) are comparable, thus allowing for meaningful comparison of experimental results from different studies irrespective of the type of scans. In addition, this study suggests that it is better to use ex vivo scanning when evaluating bone microstructure under weightlessness. However, researchers can select any type of scan depending upon the objective and the demands of the experiment.
Co-reporter:Mei-Li Liu;Jian-Qiang Wen;Yu-Bo Fan
Neurotoxicity Research 2011 Volume 20( Issue 3) pp:270-276
Publication Date(Web):2011 October
DOI:10.1007/s12640-011-9240-4
Radiofrequency electromagnetic fields (EMF) are harmful to public health, but the certain anti-irradiation mechanism is not clear yet. The present study was performed to investigate the possible protective effects of green tea polyphenols against electromagnetic radiation-induced injury in the cultured rat cortical neurons. In this study, green tea polyphenols were used in the cultured cortical neurons exposed to 1800 MHz EMFs by the mobile phone. We found that the mobile phone irradiation for 24 h induced marked neuronal cell death in the MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide) and TUNEL (TdT mediated biotin-dUTP nicked-end labeling) assay, and protective effects of green tea polyphenols on the injured cortical neurons were demonstrated by testing the content of Bcl-2 Assaciated X protein (Bax) in the immunoprecipitation assay and Western blot assay. In our study results, the mobile phone irradiation-induced increases in the content of active Bax were inhibited significantly by green tea polyphenols, while the contents of total Bax had no marked changes after the treatment of green tea polyphenols. Our results suggested a neuroprotective effect of green tea polyphenols against the mobile phone irradiation-induced injury on the cultured rat cortical neurons.
Co-reporter:Xiaoming Li, Xi Liu, Jin Huang, Yubo Fan, Fu-zhai Cui
Surface and Coatings Technology 2011 206(4) pp: 759-766
Publication Date(Web):
DOI:10.1016/j.surfcoat.2011.02.063
Co-reporter:Haifeng Liu, Xiaoming Li, Xufeng Niu, Gang Zhou, Ping Li, and Yubo Fan
Biomacromolecules 2011 Volume 12(Issue 8) pp:
Publication Date(Web):June 30, 2011
DOI:10.1021/bm200479f
Endothelialization of vascular grafts prior to implantation has been investigated widely to enhance biocompatibility and antithrombogenicity. Thrombosis of artificial vessels is typically caused by platelet adhesion and agglomeration following endothelial cells detachment when exposed to the shear stress of blood circulation. The present study thus aimed at preventing platelet adhesion and aggregation onto biomaterials before the endothelial confluence is fully achieved. We report this modification of poly(lactic-co-glycolic acid) (PLGA) scaffolds, both to impart hemocompatibility to prevent platelet adhesion and aggregation before the endothelial confluence is fully achieved and to support EC growth to accelerate endothelialization. The modification was achieved by covalent immobilization of sulfated silk fibroin on PLGA scaffolds using γ irradiation. Using phosphate-buffered saline (PBS) as an aging medium, it was demonstrated that the scaffolds prepared by γ irradiation had a good retention of sulfated silk fibroin. The systematic in vitro hemocompatibility evaluation revealed that sulfated silk fibroin covalently immobilized PLGA (S-PLGA) scaffolds-reduced platelet adhesion and activation, prolonged whole blood clotting time, activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). To evaluate further in vitro cytocompatibility of the scaffolds, we seeded vascular ECs on the scaffolds and cultured them for 2 weeks. The ECs were seen to attach and proliferate well on S-PLGA scaffolds, forming cell aggregates that gradually increased in size and fused with adjacent cell aggregates to form a monolayer covering the scaffold surface. Moreover, it was demonstrated through the gene transcript levels and the protein expressions of EC-specific markers that the cell functions of ECs on S-PLGA scaffolds were better preserved than those on PLGA scaffolds. Therefore, this study has described the generation of a vascular graft that possesses the unique ability to display excellent hemocompatibility while simultaneously supporting extensive endothelialization.
Co-reporter:Haifeng Liu, Xiaoming Li, Gang Zhou, Hongbin Fan, Yubo Fan
Biomaterials 2011 32(15) pp: 3784-3793
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.02.002
Co-reporter:LiZhen Wang;HongQuan Zhang
Science China Life Sciences 2011 Volume 54( Issue 11) pp:1036-1041
Publication Date(Web):2011 November
DOI:10.1007/s11427-011-4242-2
Woodpeckers are well able to resist head injury during repeated high speed impacts at 6–7 m s−1 with decelerations up to 1000 g. This study was designed to compare the mechanical properties, microstructures and compositions of cranial bone and beak bone of great spotted woodpecker (Dendrocopos major) and the Mongolian sky lark (Melanocorypha mongolica). Microstructures were observed using micro-computed tomography and scanning electron microscopy and their compositions were characterized by X-ray powder diffraction and Fourier-transform infrared spectroscopy. Under high stress, the cranial bone and the beak of the woodpecker exhibited distinctive mechanical features, which were associated with differences in micro-structure and composition, compared with those of the lark. Evolutionary optimization of bone micro-structure has enabled functional adaptation to the woodpecker’s specific lifestyle. Its characteristic micro-structure efficiently avoids head impact injury and may provide potential clues to the prevention of brain injury using bio-inspired designs of shock-absorbing materials.
Co-reporter:HaiJun Niu;LiFeng Li;Feng Sun;Yan Yan;YueXiang Wang
Science China Life Sciences 2011 Volume 54( Issue 11) pp:1029-1035
Publication Date(Web):2011 November
DOI:10.1007/s11427-011-4235-1
Subtle changes of articular cartilage (AC) can lead to tissue degeneration and even osteoarthritis (OA). The early degeneration of AC is closely related to a change in proteoglycans (PG) content. The observation of PG is therefore an appropriate way of studying OA and evaluating the degree of AC degeneration. In this study, 20 cartilage-bone samples were prepared from normal porcine femoral condyle cartilage and 10 samples were digested over 2 h using 0.25% trypsin solution. The dynamic process of PG-digestion was explored using a conventional A-mode ultrasound (US) experimental system with a 10 MHz center frequency. Quantitative acoustic parameters were calculated from ultrasonic radio-frequency echo signals and included US speed (USS), US amplitude attenuation coefficient (UAA) and broadband US attenuation coefficient (BUA). The experimental results showed that the conventional A-mode ultrasound is valuable for tracking the degree of PG-digestion. Histology also confirmed the validity of the ultrasound observations. For every AC sample, the degree of PG-digestion within a given time was different and was affected by individual differences. After two hours of degeneration, USS showed a mean decrease of 0.4% (P<0.05). UAA was significantly lower after a two-hour PG depletion period (from (2.45±0.23) to (2.28±0.41) dB mm−1). BUA showed no significant differences during this process. In conclusion, conventional ultrasound can provide useful information about trypsin-induced progressive PG depletion in AC and can reflect variations of PG content via the quantitative acoustic parameters USS and UAA. The results of this study may be used to identify an indirect indicator of cartilage matrix integrity and OA disease progression.
Co-reporter:Xiaoming Li;Haifeng Liu;Xufeng Niu;Qingling Feng;Fu-zhai Cui;Fumio Watari
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2011 Volume 97B( Issue 1) pp:10-19
Publication Date(Web):
DOI:10.1002/jbm.b.31773

Abstract

Microstructure is indispensable for the osteoinduction of calcium phosphate ceramics. To study how microstructure takes its role and explore the mechanism of the osteoinduction, we evaluated attachment, proliferation, alkaline phosphatase (ALP)/DNA, protein/DNA, and mineralization of human adipose-derived stem cells cultured on two kinds of biphasic calcium phosphate (BCP) ceramic discs with the same chemistry and dimension, but different microporosity and surface area. BCP-A had been found osteoinductive in vivo while BCP-B was not. During the conventional culture, ALP/DNA and protein/DNA of the cell on BCP-A with larger surface area were significantly higher than those of the cells on BCP-B. With the adsorption of the proteins in culture medium with 50% fetal bovine serum (FBS) in advance, the increments of the ALP/DNA and protein/DNA for the BCP-A were found respectively significantly more than the increments of those for BCP-B, suggesting that the larger amount of protein adsorbed on the BCP-A was crucial. More results showed that ALP/DNA and protein/DNA of the cells on the two kinds of discs presoaked in culture medium having additional rhBMP-2 were found to be both higher than those of the cells on the discs resoaked in culture medium with 50% FBS, and that those values for BCP-A increased much more. Furthermore, larger mineral content was found on BCP-A than on BCP-B at day 7. The results indicated that by increasing microporosity and thus surface areas, osteoinductive calcium phosphate ceramics concentrate more proteins, including bone-inducing proteins, and thereafter stimulate inducible cells in soft tissues to form inductive bone. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.

Co-reporter:Ping Li, Xiaoliang Feng, Xiaoling Jia, Yubo Fan
Acta Biomaterialia 2010 Volume 6(Issue 8) pp:2991-2996
Publication Date(Web):August 2010
DOI:10.1016/j.actbio.2010.02.023

Abstract

Scaffolds for tissue engineering and regenerative medicine are usually subjected to different mechanical loads during in vitro and in vivo degradation. In this study, the in vitro degradation process of electrospun poly(l-lactide-co-glycolide) (PLGA) scaffolds was examined under continuous tensile load and compared with that under no load. As PLGA degraded in phosphate-buffered saline solution (pH 7.4) at 37 °C over a 7-week period, the tensile elastic modulus and ultimate strength of the loaded specimen increased dramatically, followed by a decrease, which was much faster than that of the unloaded specimen, whereas break elongation of the loaded samples declined more quickly over the whole degradation period. Moreover, molecular weight, thermal properties and lactic acid release showed greater degradation under load. Also, a ruptured morphology was more obvious after degradation under tensile load. The results demonstrate that tensile load increased the degradation rate of electrospun PLGA and it may be necessary to consider the effects of mechanical load when designing or applying biodegradable scaffolds. Finally, some possible explanation for the faster degradation under load is given.

Co-reporter:Haijun Niu;Qing Wang;Yongping Zheng
Acta Mechanica Sinica 2010 Volume 26( Issue 1) pp:121-126
Publication Date(Web):2010 March
DOI:10.1007/s10409-009-0287-x
It is well known that subtle changes in structure and tissue composition of articular cartilage can lead to its degeneration. The present paper puts forward a modified layered inhomogeneous triphasic model with four parameters based on the inhomogeneous triphasic model proposed by Narmoneva et al. Incorporating a piecewise fitting optimization criterion, the new model was used to obtain the uniaxial modulus Ha, and predict swelling pattern for the articular cartilage based on ultrasound-measured swelling strain data. The results show that the new method can be used to provide more accurate estimation on the uniaxial modulus than the inhomogeneous triphasic model with three parameters and the homogeneous mode, and predict effectively the swelling strains of highly nonuniform distribution of degenerated articular cartilages. This study can provide supplementary information for exploring mechanical and material properties of the cartilage, and thus be helpful for the diagnosis of osteoarthritis-related diseases.
Co-reporter:Lian-wen Sun, Yu-bo Fan, De-yu Li, Feng Zhao, Tian Xie, Xiao Yang, Zhang-ting Gu
Acta Biomaterialia 2009 Volume 5(Issue 9) pp:3506-3511
Publication Date(Web):November 2009
DOI:10.1016/j.actbio.2009.04.042

Abstract

Exposure to microgravity causes a decrease in bone mass and altered bone geometry due to the lack of weight-bearing forces on the skeleton. The mechanical properties of bone are due not only to the structure and geometry, but also to the tissue properties of the bone material itself. To study the effects of microgravity on bone tissue, the mechanical properties of tail suspension rat femurs were investigated. Twelve Sprague–Dawley rats were randomly divided into two groups, tail suspension (TS) and control (CON). On days 0 and 14, the bone mineral density (BMD) of the femurs was determined by Dual Energy X-ray Absorptiometry. After 14 days, three-point bending was used to test the mechanical properties of the whole femur and nanoindentation was used to measure the mechanical properties of the bone materials. The BMD of femurs in TS was significantly lower than that in CON. In the three-point bending testing, the breaking load, stiffness and energy absorption all decreased significantly in the TS group. In the nanoindentation tests, there was no significant difference between TS and CON in elastic modulus (E), while hardness (H) was significantly decreased and E/H significantly increased in TS. Weightlessness affects the intrinsic mechanical properties of bone at the bone material level. It is necessary to investigate further the effect of microgravity on the collagen bone matrix. Nanoindentation is a relatively new technique that is useful for investigating the above changes induced by microgravity and for assessing the efficacy of intervention.

Co-reporter:Yubo Fan;Wentao Jiang;Yuanwen Zou;Jinchuan Li;Junkai Chen
Acta Mechanica Sinica 2009 Volume 25( Issue 2) pp:249-255
Publication Date(Web):2009 April
DOI:10.1007/s10409-009-0227-9
Both clinical and post mortem studies indicate that, in humans, the carotid sinus of the carotid artery bifurcation is one of the favored sites for the genesis and development of atherosclerotic lesions. Hemodynamic factors have been suggested to be important in atherogenesis. To understand the correlation between atherogenesis and fluid dynamics in the carotid sinus, the blood flow in artery was simulated numerically. In those studies, the property of blood was treated as an incompressible, Newtonian fluid. In fact, however, the blood is a complicated non-Newtonian fluid with shear thinning and viscoelastic properties, especially when the shear rate is low. A variety of non-Newtonian models have been applied in the numerical studies. Among them, the Casson equation was widely used. However, the Casson equation agrees well only when the shear rate is less than 10 s−1. The flow field of the carotid bifurcation usually covers a wide range of shear rate. We therefore believe that it may not be sufficient to describe the property of blood only using the Casson equation in the whole flow field of the carotid bifurcation. In the present study, three different blood constitutive models, namely, the Newtonian, the Casson and the hybrid fluid constitutive models were used in the flow simulation of the human carotid bifurcation. The results were compared among the three models. The results showed that the Newtonian model and the hybrid model had very similar distributions of the axial velocity, secondary flow and wall shear stress, but the Casson model resulted in significant differences in these distributions from the other two models. This study suggests that it is not appropriate to only use the Casson equation to simulate the whole flow field of the carotid bifurcation, and on the other hand, Newtonian fluid is a good approximation to blood for flow simulations in the carotid artery bifurcation.
Co-reporter:YuBo Fan;KaiHua Xiu;Xiang Dong;Ming Zhang
Science China Life Sciences 2009 Volume 52( Issue 6) pp:579-586
Publication Date(Web):2009 June
DOI:10.1007/s11427-009-0070-z
Osseointegration of implant provides a stable support for the prosthesis under functional loads. The timing of loading is a critical parameter that can govern the success of the osseointegration of implant. However, it is not clear whether the early loading can affect the success of osseointegration, or whether the no-loading healing period can be shortened. This paper presents an animal study conducted to investigate how external loads influence the osseointegration at the initial stage of healing. Titanium implants were inserted into the goat tibia laterally, and different axial loadings were applied to the implants in 4 weeks after surgery. After the 2 weeks period of early loading, animals were sacrificed and the tibia bones with the implants were cut off from the bodies. Then mechanical test was employed to find out the differences in the pull-out force, and shear strength at the bone-implant interface between the non-loaded and the loaded implants. The implant-bone interfaces were analyzed by histomorphometric method, SEM (scanning electron micrograph) and EDS (energy density spectrum). The results indicated that the bone-implant interface did not well integrate 4 weeks after surgery, and the fibrous tissue could be found at the interfaces of the specimens without loadings. While the results of loaded specimens with 10 N axial force showed that that parts of the interface were well integrated, indicating that the early mild loading may play a positive role in the process of the osseointegration. The results support that a certain range of external loading would influence the process of osseointegration, and appropriate mechanical loading can be applied to shorten the osseointegration period after surgery.
Co-reporter:Yanfang Yang, Yunhui Zhao, Gongwen Tang, Hua Li, Xiaoyan Yuan, Yubo Fan
Polymer Degradation and Stability 2008 Volume 93(Issue 10) pp:1838-1845
Publication Date(Web):October 2008
DOI:10.1016/j.polymdegradstab.2008.07.007
In vitro degradation of porous poly(l-lactide-co-glycolide)/β-tricalcium phosphate (PLGA/β-TCP) scaffolds was studied by incubating the samples in phosphate buffered saline (PBS) at 37 °C and pH 7.4 under dynamic loading with respect to static conditions for 12 weeks. Under dynamic conditions, acidity of PBS was alleviated by the better solution circulation, and water absorption of the scaffolds increased more than that under static conditions in the first 8 weeks. Changes in mass, height, diameter, relative molecular mass and its distribution also happened more remarkably under dynamic conditions. Moreover, obvious cracks and a larger amount of β-TCP particles were observed on the wall of the scaffolds after degradation for 12 weeks under dynamic loading. Compressive modulus and strength showed an increase from the beginning to the 10th week but were lower after then. Results showed that degradation of PLGA/β-TCP scaffolds under dynamic conditions exhibited a significantly faster rate than that under static conditions.
Co-reporter:Yu-Bo Fan, Ping Li, Li Zeng, Xue-Jin Huang
Polymer Degradation and Stability 2008 Volume 93(Issue 3) pp:677-683
Publication Date(Web):March 2008
DOI:10.1016/j.polymdegradstab.2007.12.015
Degradable behaviors of polymer for implantation in body should be evaluated before clinical application. The effect of continuous mechanical load on the degradation progress of poly(d,l-lactic acid) (PDLLA) foam gasket was investigated in detail by specially designed load-providing devices. While PDLLA degraded in the PBS solution (pH, 7.4) at 37 °C for 3 months, the changes of surface morphology, molecular weight, elastic modulus, tensile strength and mass loss were recorded. The results revealed that the degradation rates of PDLLA under continuous loads were obviously quicker than those without load. Moreover, the influence of tensile plus compressive load was larger than that of tensile load. It was indicated that in vivo degradation of PDLLA would not only be influenced by the local solution, but also by the surrounding load. When regulating the degradation rate of bioabsorbable polymer, one should consider the indispensable effect of load where implanted.
Co-reporter:
Science 1918 Vol 48(1249) pp:569-572
Publication Date(Web):06 Dec 1918
DOI:10.1126/science.48.1249.569-a
Co-reporter:Luoping Chen, Lisha Zheng, Jingyi Jiang, Jinpeng Gui, ... Yubo Fan
Journal of Endodontics (September 2016) Volume 42(Issue 9) pp:1355-1361
Publication Date(Web):1 September 2016
DOI:10.1016/j.joen.2016.04.025
•Calcium hydroxide activated mitogen-activated protein kinases in human DPSCs.•JNK and p38 are involved in calcium hydroxide–induced proliferation in DPSCs.•JNK, p38, and ERK involved in calcium hydroxide–induced migration, alkaline phosphatase expression, and mineralization in DPSCs.IntroductionCalcium hydroxide has been extensively used as the gold standard for direct pulp capping in clinical dentistry. It induces proliferation, migration, and mineralization in dental pulp stem cells (DPSCs), but the underlying mechanisms are still unclear. The aim of this study was to investigate the role of the mitogen-activated protein (MAP) kinase pathway in calcium hydroxide–induced proliferation, migration, osteogenic differentiation, and mineralization in human DPSCs.MethodsHuman DPSCs between passages 3 and 6 were used. DPSCs were preincubated with inhibitors of MAP kinases and cultured with calcium hydroxide. The phosphorylated MAP kinases were detected by Western blot analysis. Cell viability was analyzed via the methylthiazol tetrazolium assay. Cell migration was estimated using the wound healing assay. Alkaline phosphatase (ALP) expression was analyzed using the ALP staining assay. Mineralization was studied by alizarin red staining analysis.ResultsCalcium hydroxide significantly promoted the phosphorylation of the c-Jun N-terminal kinase (JNK), p38, and extracellular signal–regulated kinase. The inhibition of JNK and p38 signaling abolished calcium hydroxide–induced proliferation of DPSCs. The inhibition of JNK, p38, and extracellular signal–regulated kinase signaling suppressed the migration, ALP expression, and mineralization of DPSCs.ConclusionsOur study showed that the MAP kinase pathway was involved in calcium hydroxide–induced proliferation, migration, osteogenic differentiation, and mineralization in human DPSCs.
Co-reporter:Lianwen Sun, Bo Gan, Yubo Fan, Tian Xie, Qinghua Hu, Fengyuan Zhuang
Acta Astronautica (October–November 2008) Volume 63(Issues 7–10) pp:968-973
Publication Date(Web):1 October 2008
DOI:10.1016/j.actaastro.2007.12.008
Microgravity is one of the most important characteristics in space flight. Exposure to microgravity results in extensive physiological changes in humans. Bone loss is one of the changes with serious consequences; however, the mechanism retains unclear. As the origin of osteoprogenitors, mesenchymal stem cells (MSCs) may play an important role in it. After cultured under simulated microgravity (in a rotary cell culture system, RCCS), MSCs were stained using oil red O to identify adipocytes. The mRNA level of bone morphogenetic protein (BMP)-2 and peroxisome proliferators-activated receptor (PPAR) γ2 was determined by RT-PCR. Otherwise, MSCs were induced to osteogenic differentiation after microgravity culture, and then the activity of alkaline phosphatase (ALP) was determined by PNPP and the content of osteocalcin (OC) by ELISA. Furthermore, the telomerase activity in MSCs was measured by TRAP. The results showed that simulated microgravity inhibited osteoblastic differentiation and induced adipogenic differentiation accompanied by the change of gene expression of BMP-2 and PPARγ2 in MSCs. Meanwhile, the telomerase activity decreased significantly in MSCs under simulated microgravity. The reduced bone formation in space flight may partly be due to the altered potential differentiation of MSCs associated with telomerase activity which plays a key role in regulating the lifespan of cell proliferation and differentiation. Therefore, telomerase activation/replacement may act as a potential countermeasure for microgravity-induced bone loss.
Co-reporter:Lian-Wen Sun, Yun-Fei Huang, Ying Wang, Hui-Qin Luan, Yu-Bo Fan
Life Sciences in Space Research (October 2014) Volume 3() pp:18-23
Publication Date(Web):1 October 2014
DOI:10.1016/j.lssr.2014.07.002
Astronauts often suffer from microgravity-induced osteoporosis due to their time in space. Bone histomorphometry, the ‘gold standard’ technique for detecting bone quality, is widely used in the evaluation of osteoporosis. This study investigates whether μCT has the same application value as histomorphometry in the evaluation of weightlessness-induced bone loss. A total of 24 SD rats were distributed into three groups (n=8, each): tail-suspension (TS), TS plus active exercise (TSA), and control (CON). After 21 days, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) and μCT, and microstructure was measured by μCT and histomorphometry. BMD was found to have decreased significantly in TS and TSA compared with the CON group. The results of the μCT measurements showed that a change in BMD mainly occurred in the trabecular bone, and the trabecular BMD increased significantly in the TSA compared with the TS group. The comparison of μCT and histomorphometry showed that TS led to a significant decrease in bone volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N), and it led to an increase in trabecular separation (Tb.Sp). However, active exercise can prevent these changes. Significant differences in most parameters between TSA and CON were found by μCT but not by histomorphometry. Additionally, the parameters of these two methods are highly correlated. Therefore, the application value of μCT is as good as histomorphometry and DXA in the diagnosis of weightlessness-induced osteoporosis and is even better in evaluating the efficacy of exercise.
Co-reporter:Yan Huang, Xiaoling Jia, Ke Bai, Xianghui Gong, Yubo Fan
Archives of Medical Research (October 2010) Volume 41(Issue 7) pp:497-505
Publication Date(Web):October 2010
DOI:10.1016/j.arcmed.2010.10.002
Co-reporter:Xiao Yang, Lian-Wen Sun, Xin-Tong Wu, Meng Liang, Yu-Bo Fan
Acta Astronautica (November–December 2015) Volume 116() pp:286-298
Publication Date(Web):1 November 2015
DOI:10.1016/j.actaastro.2015.07.020
•A device was designed to simulate microgravity and load fluid shear simultaneously.•Osteocytes bioresponse to fluid shear under simulated microgravity was researched.•Microgravity affected molecules secretion and proteins responding to fluid shear.•Microgravity affected response of the Wnt/β-catenin signaling pathway to fluid shear.•We provided a clue for searching an efficient way against osteoporosis in space.Osteocytes sense the mechanical loading and weightlessness, and orchestrate bone remodeling by directing both osteoblast and osteoclast functions. Previous studies mostly focused on the impact of mechanical loading or microgravity on the osteocyte changes in themselves. However as the mechanosensors, it is more meaningful to make clear whether and how the mechanosensitivity of osteocytes affected by weightlessness, since the alteration of mechanosensitivity may further affect the mechanotransduction process in osteocytes, and finally altered the bone remodeling process. Whereas until now, this aspect had long been overlooked and was still not clear yet.To investigate how osteocytes respond to shear stress under weightlessness, a novel custom-made device was designed to simulate microgravity and load fluid flow on cells in vitro at the same time. The osteocyte-like cell line MLO-Y4 was loaded by this novel device at 15 dyn/cm2 shear stress with 15 rpm rotating speed. There were two loading durations for different determinations: 30 min of loading for the detection of nitric oxide and Prostaglandin E2, and 6 h of loading for the detection of three bone formation biomarkers (alkaline phosphatase, osteocalcin and procollagen type I N propeptide). In order to preliminarily explore the mechanism of this altered response to mechanical loading with different gravity in osteocytes, an observation of cytoskeleton and the determination of the elements in the Wnt/β-catenin signaling pathway were also performed after 6 h of loading. The results showed that (1) the mechanical response of both NO and PGE2 were increased higher during 15–30 min of shear stress under simulated microgravity than that under normal gravity; (2) the mechanical response of ALP activity was decreased, while that of OC and PINP content were increased by simulated microgravity. Moreover, the ALP activity and the OC content were related to the activity of Wnt signaling pathway, which plays a key role in regulating the bone formation; (3) the exploration for the mechanism of altered mechanical bio-response in osteocytes showed that F-actin filaments enhanced by shear stress under simulated microgravity were not so robust as that showed under normal gravity, and some short dendritic processes at cell periphery were only observed within the simulated microgravity groups; (4) further, the simulated microgravity significantly inhibited the mechanosensitivity of the Wnt/β-catenin signaling pathway on protein level in the osteocytes.These results suggested that the mechanosensitivity of osteocytes was altered by simulated microgravity, and this may be an adverse effect on the osteoblastic bone formation whereas be good for osteoclastogenesis. The findings in this study may provide an important clue for searching an efficient approach to prevent osteocytes from changing the orchestration for bone remodeling under microgravity, and further this prevention may finally make the physical exercises capable against bone loss under microgravity.
Co-reporter:Xiao Yang, Lian-Wen Sun, Xin-Tong Wu, Xiao-Nan Wang, Yu-Bo Fan
Acta Astronautica (March–April 2013) Volume 84() pp:237-243
Publication Date(Web):1 March 2013
DOI:10.1016/j.actaastro.2012.10.018
Osteocytes, as most abundant cells and major mechanical sensor in bone, play an important role in the mechanism of microgravity-induced bone loss. The response of osteocytes to fluid flow stress under simulated microgravity was investigated in this study. MLO-Y4, an osteocyte-like cell line, was cultured under simulated microgravity condition for 5 days. Then cells were sheared at 15 dyn/cm2 in flow chamber. After 15 min shear, nitric oxide (NO) was examined by Griess Reagent and prostaglandin E2 (PGE2) by ELISA. After 6 h shear, alkaline phosphatase (ALP) was examined by PNPP, osteocalcin (OC) and procollagen type I N propeptide (PINP) by ELISA. Cells were divided into four groups: CON (1 G with no shear), CON-S (1 G with shear), SM (simulated microgravity with no shear) and SM-S (simulated microgravity with shear). The results showed that (1) NO, ALP activity, OC and PINP increased significantly while PGE2 showed no change in SM compared with CON. (2) NO, PGE2, ALP activity and PINP increased significantly while OC decreased significantly in CON-S compared with CON. (3) NO in SM-S had no significant difference compared to SM, PGE2 and OC increased while ALP activity and PINP decreased significantly in SM-S compared with SM. (4) The increasing amplitude of PGE2 and OC, the decreasing amplitude of ALP activity in SM-S to SM was lower than that in CON-S to CON. In addition, some changes of F-actin cytoskeleton were observed by confocal microscopy. All results indicated that the response induced by fluid shear in osteocytes could be inhibited by simulated microgravity, namely the mechanosensibility of osteocytes decreased under simulated microgravity. This may partly contribute to the mechanism of microgravity-induced osteoporosis and will be helpful to find out effective description.Highlights► The mechanosensibility of osteocytes under simulated microgravity was investigated. ► Simulated microgravity inhibited shear-induced increase of signaling molecules. ► Simulated microgravity inhibited shear-induced changes of proteins in MLO-Y4. ► Simulated microgravity affected biological response of osteocytes to fluid shear.
Co-reporter:Wenxin Niu, Yang Wang, Yan He, Yubo Fan, Qinping Zhao
Human Movement Science (June 2011) Volume 30(Issue 3) pp:614-623
Publication Date(Web):1 June 2011
DOI:10.1016/j.humov.2010.10.010
The biomechanical difference between the dominant and non-dominant limb has seldom been studied during double-leg landing. The objective of this study was to evaluate the effectiveness of limb laterality on the ankle kinematics, kinetics and electromyogram (EMG) during drop landing. Sixteen healthy adults were recruited and dropped individually from platforms with three different heights (0.32 m, 0.52 m, and 0.72 m). The ground reaction force, ankle joint kinematics, and surface EMG of tibialis anterior (TA) and lateral gastrocnemius (LG) were measured in both lower extremities. Two-way analysis of variance was used to analyze the effects of laterality and dropping height. The peak angular velocities in dorsiflexion and abduction were significantly higher in the dominant ankle, whereas the pre- and post-landing EMG amplitudes of the TA were significantly higher in the non-dominant limb. Compared with the dominant side, the non-dominant ankle has a more effective protective mechanism in that excessive joint motion is restrained by greater ankle flexor activity. Compared with the non-dominant side, the dominant ankle joint is in greater injury risk during drop landing, and data measured in the dominant limb may produce more conservative conclusions for injury protection or prediction.
Co-reporter:Hui-Qin Luan, Lian-Wen Sun, Yun-Fei Huang, Xin-tong Wu, ... Yu-Bo Fan
Life Sciences in Space Research (July 2015) Volume 6() pp:15-20
Publication Date(Web):1 July 2015
DOI:10.1016/j.lssr.2015.06.001
Space flight has been shown to induce bone loss and muscle atrophy, which could initiate the degeneration of articular cartilage. Countermeasures to prevent bone loss and muscle atrophy have been explored, but few spaceflight or ground-based studies have focused on the effects on cartilage degeneration. In this study, we investigated the effects of exercise on articular cartilage deterioration in tail-suspended rats. Thirty-two female Sprague-Dawley rats were randomly divided into four groups (n=8 in each): tail suspension (TS), tail suspension plus passive motion (TSP), tail suspension plus active exercise (TSA), and control (CON) groups. In the TS, TSP, and TSA groups, the rat hindlimbs were unloaded for 21 days by tail suspension. Next, the cartilage thickness and volume, and the attenuation coefficient of the distal femur were evaluated by micro-computed tomography (μCT). Histological analysis was used to assess the surface integrity of the cartilage, cartilage thickness, and chondrocytes. The results showed that: (1) the cartilage thickness on the distal femur was significantly lower in the TS and TSP groups compared with the CON and TSA groups; (2) the cartilage volume in the TS group was significantly lower compared with the CON, TSA, and TSP groups; and (3) histomorphology showed that the chondrocytes formed clusters where the degree of matrix staining was lower in the TS and TSP groups. There were no significant differences between any of these parameters in the CON and TSA groups. The cartilage thickness measurements obtained by μCT and histomorphology correlated well. In general, tail suspension could induce articular cartilage degeneration, but active exercise was effective in preventing this degeneration in tail-suspended rats.
Co-reporter:Yunfei Huang, Huiqin Luan, Lianwen Sun, Jingfang Bi, Ying Wang, Yubo Fan
Acta Astronautica (August 2017) Volume 137() pp:373-381
Publication Date(Web):1 August 2017
DOI:10.1016/j.actaastro.2017.05.008
•Rat tail-suspension model to simulate microgravity caused serious bone loss.•Trabecular bone was primarily affected by physical loadings.•The efficacy of passive exercise or/and vibration was compared.•Vibration could enhance the efficacy of passive exercise on countering bone loss.Spaceflight induced bone loss is seriously affecting astronauts. Mechanical stimulation from exercise has been shown to restrain bone resorption as well as improve bone formation. Current exercise countermeasures in space cannot prevent it completely. Active exercise may convert to passive exercise in some ways because of the loss of gravity stimulus and inertia of exercise equipment. The aim of this study was to compare the efficacy of passive exercise or/and local vibration on counteracting the deterioration of the musculoskeletal system, including bone, muscle and tendons in tail-suspended rats. We hypothesized that local vibration could enhance the efficacy of passive exercise on countering bone loss. 40 Sprague Dawley rats were randomly distributed into five groups (n = 8, each): tail-suspension (TS), TS+35 Hz vibration (TSV), TS + passive exercise (TSP), TS + passive exercise coupled with 35 Hz vibration (TSPV) and control (CON). Passive exercise or/and local vibration was performed for 21 days. On day 0 and 21, bone mineral density (BMD) was observed by dual energy X-ray absorptiometry (DXA), and trabecular microstructure was evaluated by microcomputer tomography (μCT) analysis in vivo. Mechanical properties of tibia and tendon were determined by a mechanical testing system. Soleus and bone ash weight was tested by an electronic balance. Results showed that the passive exercise could not prevent the decrease of trabecular BMD, microstructure and bone ash weight induced by TS, whereas vibration and passive exercise coupled with local vibration (PV) could. Biomechanical properties of the tibia and tendon in TSPV group significantly increased compared with TS group. In summary, PV in this study was the best method in preventing weightlessness-induced bone loss. Consistent with our hypothesis, local vibration partly enhanced the effect of passive exercise. Furthermore, this study will be useful in improving countermeasure for astronauts, but also for the rehabilitation of disused or aged osteoporosis.
Co-reporter:Shan Tian, Lizhen Wang, Jiemeng Yang, Rui Mao, Zhaohui Liu, Yubo Fan
Journal of Biomechanics (8 February 2017) Volume 52() pp:68-73
Publication Date(Web):8 February 2017
DOI:10.1016/j.jbiomech.2016.12.012
Sigmoid sinus cortical plate dehiscence (SSCPD) is common in pulsatile tinnitus (PT) patients, and is treated through SSCPD resurfacing surgery in clinic, but the bio-mechanism is not clear as so far. This study aimed to clarify the bio-mechanism of PT sensation induced by SSCPD, and quantify the relationship of cortical plate (CP) thickness and PT sensation intensity. It was hypothesized that SSCPD would induce PT through significantly amplifying sigmoid sinus (SS) venous sound in this study. Finite element (FE) analysis based on radiology data of typical patient was used to verify this hypothesis, and was validated with clinical reports. In cases with different CP thickness, FE simulations of SS venous sound generation and propagation procedure were performed, involving SS venous flow field, vibration response of tissue overlying dehiscence area (including SS vessel wall and CP) and sound propagation in temporal bone air cells. It was shown in results that SS venous sound at tympanic membrane was 56.9 dB in SSCPD case and −45.2 dB in intact CP case, and was inaudible in all thin CP cases. It was concluded that SSCPD would directly induce PT through significantly amplifying SS venous sound, and thin CP would not be the only pathophysiology of PT. This conclusion would provide a theoretical basis for the design of SSCPD resurfacing surgery for PT patients with SSCPD or thin CP.
Co-reporter:Chi Zhang, Sheng Xie, Shuyu Li, Fang Pu, Xiaoyan Deng, Yubo Fan, Deyu Li
Journal of Biomechanics (3 January 2012) Volume 45(Issue 1) pp:83-89
Publication Date(Web):3 January 2012
DOI:10.1016/j.jbiomech.2011.10.001
It has been widely observed that atherosclerotic stenosis occurs at sites with complex hemodynamics, such as arteries with high curvature or bifurcations. These regions usually have very low or highly oscillatory wall shear stress (WSS). In the present study, 3D sinusoidally pulsatile blood flow through the models of internal carotid artery (ICA) with different geometries was investigated with computational simulation. Three preferred sites of stenoses were found along the carotid siphon with low and highly oscillatory WSS. The risk for stenoses at these sites was scaled with the values of time-averaged WSS and oscillating shear index (OSI). The local risk for stenoses at every preferred site of stenoses was found different between 3 types of ICA, indicating that the geometry of the blood vessel plays significant roles in the atherogenesis. Specifically, the large curvature and planarity of the vessel were found to increase the risk for stenoses, because they tend to lower WSS and elevate OSI. Therefore, the geometric study makes it possible to estimate the stenosis location in the ICA siphon as long as the shape of ICA was measured.
Co-reporter:Lisha Zheng, Luoping Chen, Yuchao Chen, Jinpeng Gui, Qing Li, Yan Huang, Meili Liu, Xiaolin Jia, Wei Song, Jing Ji, Xianghui Gong, Ruoshi Shi, Yubo Fan
Journal of Biomechanics (29 February 2016) Volume 49(Issue 4) pp:572-579
Publication Date(Web):29 February 2016
DOI:10.1016/j.jbiomech.2016.01.034
Shear stress is one of the main stress type produced by speech, mastication or tooth movement. The mechano-response of human periodontal ligament (PDL) cells by shear stress and the mechanism are largely unknown. In our study, we investigated the effects of fluid shear stress on proliferation, migration and osteogenic potential of human PDL cells. 6 dyn/cm2 of fluid shear stress was produced in a parallel plate flow chamber. Our results demonstrated that fluid shear stress rearranged the orientation of human PDL cells. In addition, fluid shear stress inhibited human PDL cell proliferation and migration, but increased the osteogenic potential and expression of several growth factors and cytokines. Our study suggested that shear stress is involved in homeostasis regulation in human PDL cells. Inhibiting proliferation and migration potentially induce PDL cells to respond to mechanical stimuli in order to undergo osteogenic differentiation.
Co-reporter:Xiaoyu Liu, Lizhen Wang, Chao Wang, Ganyun Sun, Songyang Liu, Yubo Fan
Journal of Biomechanics (26 April 2013) Volume 46(Issue 7) pp:1321-1327
Publication Date(Web):26 April 2013
DOI:10.1016/j.jbiomech.2013.02.006
Retinal detachment typically occurs when the retina is pulled away from its normal position by blunt trauma. It has been estimated that traumatic retinal detachments account for 10–20% of all detachments. Understanding the mechanism of traumatic retinal detachment is helpful for ophthalmologists to make a more accurate diagnosis before the symptoms develop. A finite element eye model, validated through published data, was used to simulate traumatic retinal detachment. Retinal adhesive force was incorporated into the model using breakable bonded contact. Under BB impact, global deformation was divided into four stages: compression, decompression, overshooting and oscillation. Shockwave propagation in the retina produced high strain in the retina. For an impact speed of 50 m/s, the peak strain of 0.138 in ora serrata exceeded the specified threshold for retinal break. When the eye was decompressed, negative pressure occurred around and anterior to the equator, with a minimum of −663 kPa, leading to retinal detachment. The following relative inertia motions between the retina and its supporting tissue extended the detachment. In addition, the simulations of lower shear modulus of vitreous and increased retinal adhesive force also confirm that the extent of retinal detachment is determined by negative pressure and inertial motion. In conclusion, shockwave and negative pressure contribute to retinal detachment. Shockwave propagation in the retina leads to retinal break, while negative pressure and relative inertial motion could pull the retina away from the supporting tissue. The current work would help understand the basic mechanisms underlying blunt trauma.
Co-reporter:Xiao Liu, Yubo Fan, Anqiang Sun, Xiaoyan Deng
Journal of Biomechanics (22 February 2013) Volume 46(Issue 4) pp:819-827
Publication Date(Web):22 February 2013
DOI:10.1016/j.jbiomech.2012.11.009
Extracellular adenine nucleotides ATP and ADP on vascular endothelial cells may play a role in the localization of atherogenesis by regulating the release of nitric oxide from endothelial cells and modulating intracellular calcium levels. To quantitatively investigate the concentration distribution of nucleotides on the luminal surface of the human thoracic aorta, we numerically simulated the transport of nucleotides using an aorta model constructed based on MRI images and analyzed the effects of different factors on nucleotide transport, such as ATP release rate (SATP), pulsatile flow and the absence of ATP in the main blood stream. The numerical results revealed that the combined concentration of ATP and ADP (cw−ATP+ADP) on the aortic surface varied from place to place, being relatively low in disturbed flow regions. In addition, cw−ATP+ADP was significantly affected by SATP. For relatively slow SATP, such as the moderate sigmoidal release model, cw−ATP+ADP was very low in certain flow regions with low wall shear stress. However, for very rapid SATP, such as the rapid linear release model, cw−ATP+ADP was relatively high in these same regions. The results also demonstrated that for relatively slow SATP, pulsatile blood flow enhanced cw−ATP+ADP. However, for very rapid SATP, pulsatile blood flow would reduce cw−ATP+ADP. Moreover, the absence of ATP within the main blood stream would not influence the distribution of cw−ATP+ADP. In conclusion, the concentration distribution of nucleotides along the aortic wall was quite uneven and determined by both the ATP release rate and the blood flow pattern in the aorta.
Co-reporter:Lisha Zheng, Yan Huang, Wei Song, Xianghui Gong, Meili Liu, Xiaolin Jia, Gang Zhou, Luoping Chen, Ang Li, Yubo Fan
Journal of Biomechanics (21 September 2012) Volume 45(Issue 14) pp:2368-2375
Publication Date(Web):21 September 2012
DOI:10.1016/j.jbiomech.2012.07.013
Matrix metalloproteinase (MMP)-1, 2, with their endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1, 2 are critical for extracellular matrix remodeling in human periodontal ligament (PDL) and their expression are sensitive to mechanical stresses. Shear stress as the main type of mechanical stress in tooth movement is involved in matrix turnover. However, how shear stress regulates MMPs and TIMPs system is still unclear. In this study, we investigated the effect of fluid shear stress on expression of MMP-1, 2 and TIMP-1, 2 in human PDL cells and the possible roles of mitogen-activated protein kinases in this process. Three levels of fluid shear stresses (6, 9 and 12 dyn/cm2) were loaded on PDL cells for 2, 4, 8 and 12 h. The results indicated that fluid shear stress rearranged cytoskeleton in PDL cells. Fluid shear stress increased expression of MMP-1, 2, TIMP-1 and suppressed TIMP-2 expression. MAP kinases including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 were activated rapidly by fluid shear stress. The ERK inhibitor blocked fluid shear stress induced MMP-1 expression and P38 inhibitor reduced fluid shear stress stimulated MMP-2 expression. Our study suggested that fluid shear stress involved in PDL remodeling via regulating MMP-1, 2 and TIMP-1, 2 expression. ERK regulated fluid shear stress induced MMP-1 expression and P38 play a role in fluid shear stress induced MMP-2 upregulation.
Co-reporter:Junchao Guo, Lizhen Wang, Zhongjun Mo, Wei Chen, Yubo Fan
Journal of Biomechanics (18 September 2015) Volume 48(Issue 12) pp:3170-3177
Publication Date(Web):18 September 2015
DOI:10.1016/j.jbiomech.2015.07.004
Valgus foot (VF) is the most common foot deformity in children with cerebral palsy (CP), which seriously affects the foot balance in standing and posture control in walking. Little information about the locus and stress of internal bones was available. To accurately describe the biomechanical behavior of the internal bones of VF in CP, we compared the locus and stress of internal bones between the normal foot (NF) and VF by finite element models. Compared with the NF, displacement of the talus and navicular drop in VF increased by 109% and 171% in vertical direction respectively, and the locus of talus had a tendency to clockwise rotation and downward movement in coronal plane. In addition, the abduction angle of forefoot in VF increased up to 10.3°, which was twice more than that in the NF. Moreover, the lateral metatarsophalangeal joints were upward tilted 6.3° comparing with touchdown posture of NF, and peak von Mises stress of the internal bones in VF model concentrated on the fourth metatarsal. The simulation showed that locus of the forefoot, downward rotation of talus head and navicular drop were meaningful to quantify the collapse of medial longitudinal arch. It would provide some suggestions to the rehabilitation treatments of the CP children's VF.
Co-reporter:X.N. Gu, H.M. Guo, F. Wang, Y. Lu, W.T. Lin, J. Li, Y.F. Zheng, Y.B. Fan
Materials Letters (15 April 2017) Volume 193() pp:
Publication Date(Web):15 April 2017
DOI:10.1016/j.matlet.2017.01.136
•Silane coatings were electrodeposited on magnesium alloys.•The resulted coatings had good durability and anti-corrosion properties.•The resulted coatings had good cyto- and hemo-compatibility.•The optimal electrodeposition voltage is −2.0 V.The major obstacle to the clinical use of magnesium alloys is their fast degradation behaviors. In the present study, the triethoxy(octyl)silane coatings were electrodeposited on magnesium alloy to improve the corrosion resistance and biocompatibility. The effects of the electrodeposition potential on the corrosion properties of the silane coatings were investigated. The resulted coatings were characterized by SEM, FTIR, surface hydrophobicity, in addition, the corrosion behaviors and biocompatibilities were also evaluated. The results indicated that the coatings deposited at −2.0 V were more corrosion resistant than the other two silane coatings. Furthermore, the silane coatings showed good biocompatibilities, as demonstrated by significant increased cell viability, reduced hemolysis and platelet adhesion.
Co-reporter:Hui-Qin Luan, Lian-Wen Sun, Yun-Fei Huang, Ying Wang, Colin J. McClean, Yu-Bo Fan
Advances in Space Research (1 June 2014) Volume 53(Issue 11) pp:
Publication Date(Web):1 June 2014
DOI:10.1016/j.asr.2014.02.014
Osteopenia is a pathological process that affects human skeletal health not only on earth but also in long-time spaceflight. Micro-computed tomography (micro-CT) is a nondestructive method for assessing both bone quantity and bone quality. To investigate the characteristics of micro-CT on evaluating the microgravity-induced osteopenia (e.g. early detection time and the sensitive parameters), the bone loss process of tail-suspended rats was monitored by micro-CT in this study. 8-Week-old female Sprague Dawley rats were divided into two groups: tail suspension (TS) and control (CON). Volumetric bone mineral density (vBMD) and microstructure of the femur and tibia were evaluated in vivo by micro-CT at 0, 7, 14, 22 days. Biomechanical properties of the femur and tibia were determined by three-point bending test. The ash weight of bone was also investigated. The results showed that (1) bone loss in the proximal tibia appeared earlier than in the distal femur. (2) On day 7, the percent bone volume (BV/TV) of the tibia 15.44% decreased significantly, and the trabecular separation (Tb.Sp) 30.29% increased significantly in TS group, both of which were detected earlier than other parameters. (3) Biomechanical properties (e.g. femur, −22.4% maximum load and −23.75% Young’s modulus vs. CON) and ash weight of the femur and tibia decreased significantly in the TS group in comparison to CON group. (4) vBMD of the femur and tibia were clearly related to bone ash and dry weight (r = 0.75–0.87, p < 0.05). (5) BV/TV of both femur and tibia were clearly related to maximum load and Young’s modulus (r = 0.66–0.87, p < 0.05). Similarly, trabecular vBMD and BV/TV of the femur and tibia were clearly related to Young’s modulus (r = 0.73–0.89, p < 0.05). These indicated that BV/TV and Tb.Sp were more sensitive than other parameters for evaluating bone loss induced by tail suspension, moreover, trabecular vBMD and other parameters might be used to evaluate bone strength. Therefore, micro-CT is a reliable and sensitive method for predicting unloading-induced bone loss in small animals.
Co-reporter:Xufeng Niu, Rui Fan, Feng Tian, Xiaolin Guo, Ping Li, Qingling Feng, Yubo Fan
Materials Science and Engineering: C (1 April 2017) Volume 73() pp:
Publication Date(Web):1 April 2017
DOI:10.1016/j.msec.2016.12.079
•Calcium concentrations have important influence on collagen mineralization.•Low concentration of calcium results in well collagen self-assembly while poor mineral crystallization.•High concentration of calcium hinders collagen self-assembly, whereas it is benefited to mineral crystallization.Mineralization of collagen fibrils is a regular combination process of organic and mineral components mainly involving calcium, phosphate and collagen. We report the influence of calcium to the self-assembly of collagen by changing the concentration of calcium ion in the process of mineralization. Low concentration of calcium results in the well collagen self-assembly while poor mineral crystallization. Relatively, high concentration of calcium can hinder collagen self-assembly, whereas it is benefited to mineral crystallization. We also reveal that collagen self-assembly happens in advance of the formation of better mineral crystals. These results interpret the mechanism of collagen mineralization further.
Co-reporter:Xili Ding, Xing Wei, Yan Huang, Changdong Guan, Tongqiang Zou, Shuo Wang, Haifeng Liu and Yubo Fan
Journal of Materials Chemistry A 2015 - vol. 3(Issue 16) pp:NaN3188-3188
Publication Date(Web):2015/03/06
DOI:10.1039/C5TB00046G
Demineralized bone matrix (DBM) has been widely used for bone regeneration due to its osteoinductivity and osteoconductivity. However, the use of DBM powder is limited due to the difficulties in handling, the tendency to migrate from graft sites and the lack of stability after surgery. In this study, a mechanically stable, salt-leached porous silk fibroin carrier was used to improve the handling properties of DBM powder and to support the attachment, proliferation and osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). The DBM-silk fibroin (DBM/SF) scaffolds were fabricated with different contents of DBM powder (0%, 10%, 20%, 40% and 80% DBM/SF scaffolds). It was found that the DBM/SF scaffolds could form a stable composite preventing the migration of DBM powder. Moreover, the microarchitecture and mechanical properties of the scaffolds were influenced by the DBM powder. rBMSCs were seeded on the DBM/SF scaffolds and cultured for 14 days. Cell proliferation assays and cell morphology observations indicated that 20% DBM/SF scaffolds exhibited good cell attachment and proliferation. In addition, compared with the other groups, the cellular function was more actively exhibited on 20% DBM/SF scaffolds, as evident by the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for osteoblast-related gene markers (e.g. COL1A1, ALP and cbfa1), the immunocytochemical evaluations of osteoblast-related extracellular matrix components (e.g. COL1A1, OCN and ONN) and the ALP activities. All the data suggested that DBM powder could be delivered using a silk fibroin carrier with improved handling characteristics and that 20% DBM/SF scaffolds had great potential as osteogenesis promoting scaffolds for successful applications in bone regeneration.
Co-reporter:Fang Zhou, Xiaoling Jia, Qingmao Yang, Yang Yang, Yunhui Zhao, Yubo Fan and Xiaoyan Yuan
Biomaterials Science (2013-Present) 2016 - vol. 4(Issue 5) pp:NaN856-856
Publication Date(Web):2016/04/08
DOI:10.1039/C5BM00629E
Manipulation of gene expression by means of microRNAs (miRNAs) is one of the emerging strategies to treat cardiovascular and cancer diseases. Nevertheless, efficient delivery of miRNAs to a specific vascular tissue is limited. In this work, a short peptide Arg-Glu-Asp-Val (REDV) was linked to trimethyl chitosan (TMC) via a bifunctional poly(ethylene glycol) (PEG) linker for the targeted delivery of microRNA-126 (miRNA-126) to vascular endothelial cells (VECs). The morphology, serum stability and cytotoxicity of the polyplex/miRNA complexes, namely, TMC/miRNA, TMC-g-PEG/miRNA and TMC-g-PEG-REDV/miRNA, were investigated along with the cellular uptake, proliferation and in vitro miRNA transfection efficiency. By REDV modification, the TMC-g-PEG-REDV/miRNA complex showed negligible cytotoxicity, increased expression of miRNA-126 and enhanced VEC proliferation compared with the TMC/miRNA and TMC-g-PEG/miRNA complexes. In particular, the approaches adopted for the miRNA delivery and targeted peptide REDV modification promote the selective uptake and the growth of VECs over vascular smooth muscle cells. It was suggested that the REDV peptide-modified TMC-g-PEG polyplex could be potentially used as a miRNA carrier in artificial blood vessels for rapid endothelialization.
Co-reporter:Zhiyong Qian, Haiping Wang, Xiaoye Tuo, Hongyan Guo, Peng Xu, Donghua Liu, Yen Wei, Haifeng Liu, Yubo Fan and Ximin Guo
Journal of Materials Chemistry A 2017 - vol. 5(Issue 25) pp:NaN4851-4851
Publication Date(Web):2017/05/11
DOI:10.1039/C7TB00802C
Controlling severe hemorrhages remains a challenge. Successful hemorrhage control depends on the speed and quality of blood clot formation. Fast deprivation of water from blood leads to the concentration of blood cells and coagulation factors and thus triggers blood clot formation. This inspired us to develop a new hemostatic material. In this study, we grafted sodium polyacrylate (SPA) onto the backbone of chitosan (CTS) and crosslinked with methacrylic anhydride-modified polyethylene glycol (MAAPEG) to provide a flexible and elastic inter-chain connection between SPA and CTS chains in the presence of a blowing agent to achieve a porous structure. By a simple one-pot reaction, we fabricated a soft, elastic porous xerogel sponge that could reach maximum water absorbency of 180 in less than 200 seconds. This SPA-co-chitosan xerogel sponge demonstrated superior hemostatic properties in thromboelastography (TEG®) test and in a rabbit lethal extremity arterial bleeding model as compared to zeolite granules, kaolin gauze, and chitosan granules. Furthermore, this hemostat worked as a whole to transfer external pressure to the bleeding area and was adhesive to wet wound tissue to seal the bleeding site. In general, the SPA-co-CTS sponge demonstrates a fast and powerful hemostatic effect both in vitro and in vivo, which is superior over the existing commercial products. It might be a promising first-aid device for severe hemorrhage control.
Poly(l-lactide)
Poly[oxy[(1S)-1-methyl-2-oxo-1,2-ethanediyl]]
Triphosphate
Titanium nickelide
Angiotensin II
Triphosphoric acid
Heparin sodium
L-lactate dehydrogenase from rabbit muscle ~140 U/mg