Co-reporter:Dongli Jiang;Huan Zhao;You Yang;Yuda Zhu;Xiaoqin Chen;Jing Sun;Kui Yu;Xingdong Zhang
Journal of Materials Chemistry B 2017 vol. 5(Issue 20) pp:3749-3757
Publication Date(Web):2017/05/24
DOI:10.1039/C6TB03184F
Defect-related fluorescent HAp materials, which require no toxic metal ions or photobleaching fluorescent organic dyes, are expected to be excellent fluorescent probes in biological fields. However, the luminescent mechanism is poorly understood, making it difficult to adjust their emission performance for better applications in bioimaging. Herein, a novel luminescent mechanism for defect-related HAp fluorescent materials obtained from a typical hydrothermal process was revealed. N-Rich carbon dots (CDs), rather than the reported CO2˙−, were confirmed as the luminescence centers responsible for self-activated luminescence. The mode in which the N-rich CDs and HAp host combined might be through CDs (mainly polymer clusters and/or molecular fluorophores constituents) becoming trapped in the HAp crystal structure. This study should inspire the design of fluorescent HAp materials with tunable fluorescence emissions due to the diverse synthetic methods and tunable fluorescence emission of CDs.
Co-reporter:Huaifa Zhang;Fangzhu Qing;Huan Zhao;Ming Liu;Xingdong Zhang
Journal of Materials Chemistry B 2017 vol. 5(Issue 6) pp:1205-1217
Publication Date(Web):2017/02/08
DOI:10.1039/C6TB01401A
Nano hydroxyapatite particles (n-HA) have been reported to promote osteogenic activities of bone-related cells, while inhibiting tumor cell growth, and the biological effects of n-HA are related with the particle size, dose, culture time and cell type. In this work, we prepared n-HA with a strictly controlled rod-like shape and adjustable sizes without any surface chemical contaminations. Using the prepared n-HA, we investigated the size and dose effect of the nano particles on pre-osteoblasts for up to 7 days. We probed cell proliferation and gene expression in the presence of n-HA, the cellular uptake pathways of n-HA particles, as well as the extracellular and intracellular [Ca2+] ([Ca2+]i) changes caused by the particles, in order to get a better understanding of the biological effects of n-HA of various sizes. The n-HA exhibited size- and dose-dependent impacts on MC3T3-E1 proliferation, intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential, and osteogenic gene expression. 40 nm n-HA caused the slowest MC3T3-E1 growth, the highest intracellular ROS concentration, the largest mitochondrial membrane potential loss and the lowest level of osteogenic gene expression among the samples. The cytotoxicity of 40 nm n-HA increased with the dose and culture time. 70 nm n-HA showed beneficial effects on MC3T3-E1 growth, but the positive effect disappeared at the highest concentration on day 7. 100 nm n-HA promoted cell growth and the promoting effect increased with the dose. Cells cultured with 100 nm n-HA expressed the highest level of osteogenic gene expression among the experimental groups. We discovered that the presence of n-HA increased [Ca2+]i but did not elevate extracellular [Ca2+]. The [Ca2+]i increased as the n-HA size decreased. We also found that n-HA may enter cells through two pathways and that the amount of engulfed particles depended on the particle size. The internalized n-HA particles located in the cytosol, endosomes, lysosomes and nuclei. The particles dissolved in lysosomes and raised [Ca2+]i, which correlated with the cell death and osteogenic gene expression. In conclusion, the particle size, dose, and culture time influenced the biological effects of n-HA on ME3T3-E1 cells, probably by changing the [Ca2+]i in the cells instead of the extracellular [Ca2+].
Co-reporter:Ke Yang;Jing Sun;Dan Wei;Lu Yuan;Jirong Yang;Likun Guo;Xingdong Zhang
Journal of Materials Chemistry B 2017 vol. 5(Issue 44) pp:8707-8718
Publication Date(Web):2017/11/15
DOI:10.1039/C7TB02348K
Type II collagen is a prospective chondro-inductive matrix for bone marrow mesenchymal stem cells (BMSCs), a key component of the extracellular matrix of cartilage; however, its application is limited by deficient fibrillogenesis and gelation. Herein, type II collagen methacrylamide (Col-II-MA) was synthesized by an amidation reaction between the ε-amino groups on collagen lysine and methacrylic anhydride to enable photo-crosslinking of the collagen, thus accomplishing a one-step preparation of mono-component type II collagen hydrogel for the first time. BMSCs encapsulated within the Col-II-MA hydrogel exhibited accelerated proliferation and morphological changes that are similar to chondrogenesis, as well as up-regulated expression of chondrogenic genes and remarkable secretion of the cartilaginous matrix. These results demonstrated that this effective synthetic approach facilitated the formation of photo-active type II collagen hydrogel with a well-preserved triple helical conformation, which provides BMSCs with a favorable microenvironment for growth and the essential chondro-inductive matrix for differentiation. Furthermore, the hydrogel is applicable to microfabrication techniques and displays promise for future applications in microscale tissue engineering.
Co-reporter:Jing Sun;Dan Wei;Ke Yang;You Yang;Xiaolu Liu;Xingdong Zhang
Journal of Materials Chemistry B 2017 vol. 5(Issue 40) pp:8060-8069
Publication Date(Web):2017/10/18
DOI:10.1039/C7TB01458A
Biomimetic multicellular complex tissues can be obtained via 3D microfabrication approaches, although the lack of active materials that meet the needs of both molding and the maintenance of cell function is the main bottleneck in their application. The development of 3D cell culture platforms, which are suitable for multiple cell types and various microfabrication technologies, would open the way to the biomimetic construction of multicellular complex tissues. In this study, a MMP-sensitive photocrosslinkable hydrogel system based on methacrylated alginate, which is suitable for the survival of multiple cell types and can be employed in a variety of micro-manufacturing technologies, was designed for the construction of 3D microfeatures to meet both the demands of molding and the requirement for biomimetic function. By employing the characteristics of photocrosslinking and ion crosslinking, the gel system was combined with a variety of microfabrication techniques to construct biomimetic microstructures with a spatial distribution of multiple types of cell. The diversity of shapes and cell types in these assemblies, as well as the maintenance of cell activity, collectively show that the functional MMP-sensitive gel system has the potential to be used as a cell culture platform for the construction of tissue microstructures.
Co-reporter:Meiling Zhong, Dan Wei, You Yang, Jing Sun, Xuening Chen, Likun Guo, Qingrong Wei, Yizao Wan, Hongsong FanXingdong Zhang
ACS Applied Materials & Interfaces 2017 Volume 9(Issue 4) pp:
Publication Date(Web):January 11, 2017
DOI:10.1021/acsami.6b15697
Tissue engineering aims to generate functional tissue constructs in which proper extracellular matrix (ECM) for cell survival and establishment of a vascular network are necessary. A modular approach via the assembly of modules mimicking the complex tissues’ microarchitectural features and establishing a vascular network represents a promising strategy for fabricating larger and more complex tissue constructs. Herein, as a model for this modular tissue engineering, engineered bone-like constructs were developed by self-assembly of osteon-like modules and fast degradable gelatin microspheres. The collagen microspheres acting as osteon-like modules were developed by seeding human umbilical vein endothelial cells (HUVECs) onto collagen microspheres laden with human osteoblast-like cells (MG63) and collagenase. Both HUVECs and MG63 cells were well spatially patterned in the modules, and collagen as ECM well supported cell adhesion, spreading, and functional expression due to its native RGD domains and enzymatic degradation activity. The patterned modules facilitated both the cellular function expression of osteogenic MG63 cells and vasculogenic HUVECs; that is, the osteon-like units were successfully achieved. The assembly of the osteon-like modules and fast degradable gelatin microspheres promoted the vascularization, thus facilitating the osteogenic function expression. The study provides a highly efficient approach to engineering complex 3D tissues with micropatterned cell types and interconnected channels.Keywords: cell-laden hydrogel; microfabrication; micromodules; osteon-like; vascularization;
Co-reporter:Xiaolu Liu, Yicong Zuo, Jing Sun, Zhenzhen Guo, Hongsong Fan, Xingdong Zhang
Carbohydrate Polymers 2017 Volume 178(Volume 178) pp:
Publication Date(Web):15 December 2017
DOI:10.1016/j.carbpol.2017.09.014
•Desirable bioink with sufficient initial strength and bioactivity was generated.•Lyase digestion endowed cell with space for proliferation and function fulfillment.•Osteon-like microfibers were constructed based on microfluidic biofabrication.•Diverse assembling holds potential for fabricating complex tissue-like constructs.Bioink development is vital in biofabriacation for generating three-dimensional (3D) tissue-like constructs. As potential candidates of bioinks, hydrogels need to meet the requirements of good moldability, initially strong mechanical properties and prominent bioactivity to guarantee cell vitality and further assembly. Enzyme-induced dynamic degradation is an efficient and biocompatible approach to improve the bioactivity of hydrogels through releasing space continuously for cell proliferation and promoting the functional establishing of engineered tissue. Here a novel bioink was designed by introducing alginate lyase into composite Alginate-GelMA hydrogels. Results showed that bioink with proper lyase content exhibited desirable modability and cytocompatibility. Then cell-laden osteon-like microfibers were engineered with the microfluidic device and diverse complex 3D constructs were also successfully assembled. This degradation-regulated bioink showed great promise in a variety of applications in tissue engineering and biomedical investigation.
Co-reporter:Yicong Zuo, Xiaoheng He, You Yang, Dan Wei, Jing Sun, Meiling Zhong, Rui Xie, Hongsong Fan, Xingdong Zhang
Acta Biomaterialia 2016 Volume 38() pp:153-162
Publication Date(Web):1 July 2016
DOI:10.1016/j.actbio.2016.04.036
Abstract
Microfluidic-based fiber system displays great potential in reconstructing naturally complex tissues. In these systems, fabrication of the basic fiber is a significant factor in ensuring a functional construction. The fiber should possess the strong mechanical rigidity for assembly, predefined microenvironment for cell spatial distribution and high biocompatibility for cell functional expression. Herein we presented a composite material by the combination of methacrylated gelatin (GelMA) and alginate for fiber engineering with capillary microfluidic device. Being regulated by GelMA incorporation, the composite hydrogels exhibited higher mechanical moduli, better stretching performance, and lower swelling compared to pure alginate one. On the basis of the composite material and capillary microfluidic device, we constructed the double-layer hollow microfibers to simulate complex tissues. The microfibers could be precisely controlled in size and multi-layered structure by varying flow rates and outlet diameter, and it showed satisfied application in woven-structure assembly. As an example to mimic a functional tissue, a biomimetic osteon-like structure was fabricated by encapsulating human umbilical vascular endothelial cells (HUVECs) in middle layer to imitate vascular vessel and human osteoblast-like cells (MG63) in the outer layer to act role of bone. During the incubation period, both MG63 and HUVECs exhibited not only a robust growth, but also up-regulated gene expression. These results demonstrated this microfluidic-based composite microfibers system is a promising alternative in complex tissue regeneration.
Statement of Significance
Cell-laden microfibers based on microfluidic device is attracting interest for reconstructing naturally complex tissues. One shortage is the lack of suitable materials which satisfy microfluidic fabrication and cell biofunctional survival. This study reports the first combination of alginate-GelMA composite and capillary-based microfluidic technology. The composite materials possess high mechanical properties for fabrication and assembly, and tunable environment for cell spatial encapsulation. Significantly, the engineered double-layer hollow microfiber with osteon-like structure showed enhanced cellular bioactivity and realized initially functional establishment. This microfluidic-based composite microfiber not only explores a competitive candidate in complex tissues reconstruction, but also expands the biological application of microfluidic technology. This developing interdisciplinary area should be widely interested to the readers of biofabrication, biomaterials and tissue engineering.
Co-reporter:Yu-Da Zhu, Su-Ping Chen, Huan Zhao, You Yang, Xiao-Qin Chen, Jing Sun, Hong-Song FanXing-Dong Zhang
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 50) pp:
Publication Date(Web):November 23, 2016
DOI:10.1021/acsami.6b11378
A medical nanoplatform with small size, low cost, biocompatibility, good biodegradability, and, in particular, multifunctionality has attracted much attention in the exploration of novel therapeutic methodologies. As an emerging material of self-assembled porous structure, metal–organic frameworks (MOFs) have high expectations because of their special properties compared to traditional porous materials. Therefore, integration of MOFs and functional materials is leading to the creation of new multifunctional composites/hybrids. Photothermal therapy (PTT), using near-IR (NIR) laser-absorbing nanomaterials as PTT agents, has shown encouraging therapeutic effects to photothermally ablate tumors. However, the most of widely used PTT agents are inorganic materials and nonbiodegradable. Herein, uniform polypyrrole (PPy) nanoparticles (NPs) with good biodegradability were synthesized by a microemulsion method. The PPy NPs were further coated with the mesoporous iron-based MOF structure MIL-100 by interaction between PPy NPs and MIL-100 precursors at room temperature. As a multifunctional nanoplatform, an anticancer drug could easily be loaded into the mesopores of the MIL-100 shell. The PPy core, as an organic photothermal agent, is able to photothermally ablate cancer cells and improve the efficacy of chemotherapy under NIR irradiation. The composites showed an outstanding in vivo synergistic anticancer capacity. Our work could encourage further study in the construction of a synergetic system using MOFs and organic PTT agents.Keywords: drug delivery; metal−organic framework; MIL-100; multifunctional hybrids; photothermal therapy; polypyrrole;
Co-reporter:Dan Wei, Wenqian Xiao, Jing Sun, Meiling Zhong, Likun Guo, Hongsong Fan and Xingdong Zhang
Journal of Materials Chemistry A 2015 vol. 3(Issue 14) pp:2753-2763
Publication Date(Web):13 Feb 2015
DOI:10.1039/C5TB00129C
Surface tension driven assembly is a simple and rapid strategy in “modular” tissue engineering to fabricate three-dimensional (3D) structures with predefined geometrical and biological features. Besides the biocompatibility for encapsulated cells, the mechanical and hydrophilic properties of the microgel are the utmost two factors for assembly and structure preservation. Herein, we developed a new composite hydrogel based on photocrosslinkable methacrylated gelatin (GelMA) and methacrylated alginate (AlgMA) for modular tissue engineering assembly. Based on the high cellular bioactivity of GelMA, inflexible AlgMA with a large number of hydrophilic groups was introduced to optimize the hydrogel assembly performance. The results revealed that the mechanical stiffness, swelling ratio and hydrophilicity were improved greatly, and the nutrient permeability as well as the cellular activity remained at a relatively high level simultaneously. The enhanced stiffness and hydrophilicity were helpful for the surface tension driven assembly, and the high nutrient permeability was conducive to the activity of encapsulated cells. Moreover, microgels with different shapes were fabricated, and microengineered complex structures constructed with spatial organized cell distribution and specific functions, such as osteon-like structure containing both osteogenic and vascularized area, were successfully generated by “Lock and key” and “Concentric double-ring” assemblies. The composite hydrogel provides a potential candidate material for modular tissue engineering.
Co-reporter:Yicong Zuo, Xiaolu Liu, Dan Wei, Jing Sun, Wenqian Xiao, Huan Zhao, Likun Guo, Qingrong Wei, Hongsong Fan, and Xingdong Zhang
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 19) pp:10386
Publication Date(Web):April 30, 2015
DOI:10.1021/acsami.5b01433
Modular tissue engineering holds great potential in regenerating natural complex tissues by engineering three-dimensional modular scaffolds with predefined geometry and biological characters. In modular tissue-like construction, a scaffold with an appropriate mechanical rigidity for assembling fabrication and high biocompatibility for cell survival is the key to the successful bioconstruction. In this work, a series of composite hydrogels (GH0, GH1, GH2, and GH3) based on a combination of methacrylated gelatin (GelMA) and hydroxyapatite (HA) was exploited to enhance hydrogel mechanical rigidity and promote cell functional expression for osteon biofabrication. These composite hydrogels presented a lower swelling ratio, higher mechanical moduli, and better biocompatibility when compared to the pure GelMA hydrogel. Furthermore, on the basis of the composite hydrogel and photolithograph technology, we successfully constructed an osteon-like concentric double-ring structure in which the inner ring encapsulating human umbilical vascular endothelial cells (HUVECs) was designed to imitate blood vessel tubule while the outer ring encapsulating human osteoblast-like cells (MG63s) acts as part of bone. During the coculture period, MG63s and HUVECs exhibited not only satisfying growth status but also the enhanced genic expression of osteogenesis-related and angiogenesis-related differentiations. These results demonstrate this GelMA–HA composite hydrogel system is promising for modular tissue engineering.Keywords: hydroxyapatite; methacrylated gelatin; modular tissue engineering; osteon;
Co-reporter:Meiling Zhong, Jing Sun, Dan Wei, Yuda Zhu, Likun Guo, Qingrong Wei, Hongsong Fan and Xingdong Zhang
Journal of Materials Chemistry A 2014 vol. 2(Issue 38) pp:6601-6610
Publication Date(Web):07 Aug 2014
DOI:10.1039/C4TB00887A
Hydrogels hold great promise for tissue engineering and as cell delivery vehicles, but their application is greatly limited by the mass depletion of cells after encapsulation due to their low cell affinity and high cell constraints. In this study, using human osteoblast-like cells (MG63) as a model for anchorage-dependent cells (ADCs), alginate hydrogels incorporated with collagen microcarriers (MCs) and collagenase (GCE) were constructed to promote the cellular functional establishment. In this system, the cell-laden microcarriers as cellular ‘anchors’ provided a cell-affinitive interface between cells and hydrogels, while the collagenase promoted the degradation of collagen microspheres and thus provided adequate room for cell spreading and migration. Compared to the pure alginate hydrogel (Gel), the alginate hydrogel/microcarrier composite (GC) improved initial cell spreading by supplying a cell adhesive interface, while GCE with both microcarriers and collagenase exhibited much better cell spreading, proliferation and differentiation, which is attributed to the sustainable supply of both a cell adhesive interface and cell spreading room. The composites showed potential as an injectable vehicle for the conveyance of ADCs and tissue engineering.
Co-reporter:Huan Zhao, Yu-Da Zhu, Jing Sun, Dan Wei, Ke-Feng Wang, Ming Liu, Hong-Song Fan and Xing-Dong Zhang
Chemical Communications 2014 vol. 50(Issue 83) pp:12519-12522
Publication Date(Web):28 Aug 2014
DOI:10.1039/C4CC05088F
Hollow hydroxyapatite nanospheres were prepared by a two-phase approach by controlling nucleation and crystal growth processes. The cavities of hollow HA provide potential applications as new kinds of containers for carrying, filling in, or encapsulating other materials, thus constructing a multifunctional system with good biocompatibility.
Co-reporter:Jing Sun, Dan Wei, Yuda Zhu, Meiling Zhong, Yicong Zuo, Hongsong Fan, Xingdong Zhang
Biomaterials 2014 35(17) pp: 4759-4768
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.02.041
Co-reporter:Chaoyong Zhao, Hongfang Zhang, Bing Cai, Guanglin Wang, Hongsong Fan and Xingdong Zhang
Biomaterials Science 2013 vol. 1(Issue 7) pp:703-710
Publication Date(Web):27 Mar 2013
DOI:10.1039/C3BM00199G
In this study, a porous PLGA/Ti biphasic scaffold was prepared and its potential to repair osteochondral defects was evaluated. The microstructure and mechanical properties of porous PLGA and porous Ti and their interface were characterized. The as-prepared biphasic scaffolds were implanted into rabbit knees for 1 and 3 months (PLGA/Ti group), and the porous PLGA (PLGA group) or empty defect (Untreated group) was also used. The results showed that both porous PLGA and porous Ti had an interconnected porous structure. The mechanical strength of porous PLGA and porous Ti was similar to that of cartilage and subchondral bone, respectively. The interface analysis revealed that the as-prepared biphasic scaffold had good overall integrity and interface stability. The gross observation and histological evaluation of specimens showed that hyaline-like cartilage filled the defects to a certain extent at 3 months for both PLGA/Ti and PLGA groups while the defects remained in an untreated group. In the PLGA/Ti group, better cartilage and subchondral bone repair was observed, and quantitative macroscopic and histological score evaluations confirmed this result, indicating that the porous biphasic PLGA/Ti scaffold had good biocompatibility and the best osteochondral defect repair ability in this study. The as-prepared porous biphasic scaffold showed the potential to be used in osteochondral tissue engineering for osteochondral defect repair.
Co-reporter:Xin Duan, Xiangdong Zhu, Xingxing Dong, Jing Yang, Fuguo Huang, Shiqiang Cen, Frankie Leung, Hongsong Fan, Zhou Xiang
Materials Science and Engineering: C 2013 Volume 33(Issue 7) pp:3951-3957
Publication Date(Web):October 2013
DOI:10.1016/j.msec.2013.05.040
•We developed a novel type I collagen/glycosaminoglycan porous titanium biphasic scaffold.•We used this biphasic scaffold to repair osteochondral defects in an animal model with bone marrow stem cells.•The abundant subchondral bone formation was observed in osteophase.•Better cartilage repairing results were gained from biphasic scaffold with bone marrow stem cells in chondrophase.•This biphasic scaffold combined with bMSCs shows a high potential to repair large osteochondral defects.The limited repair potential of articular cartilage, which hardly heals after injury or debilitating osteoarthritis, is a clinical challenge. The aim of this work was to develop a novel type I collagen (Col)/glycosaminoglycan (GAGs)-porous titanium biphasic scaffold (CGT) and verify its ability to repair osteochondral defects in an animal model with bone marrow stem cells (bMSCs) in the chondral phase. The biphasic scaffold was composed of Col/GAGs as chondral phasic and porous titanium as subchondral phasic. Twenty-four full-thickness defects through the articular cartilage and into the subchondral bone were prepared by drilling into the surface of the femoral patellar groove. Animals were assigned to one of the three groups: 1) CGT with bMSCs (CGTM), 2) only CGT, and 3) no implantation (control). The defect areas were examined grossly, histologically and by micro-CT. The most satisfied cartilage repairing result was in the CGTM group, while CGT alone was better than the control group. Abundant subchondral bone formation was observed in the CGTM and CGT groups but not the control group. Our findings demonstrate that a composite based on a novel biphasic scaffold combined with bMSCs shows a high potential to repair large osteochondral defects in a canine model.
Co-reporter:Yicong Zuo, Wenqian Xiao, Xiaoqin Chen, Yajun Tang, Hongrong Luo and Hongsong Fan
Chemical Communications 2012 vol. 48(Issue 26) pp:3170-3172
Publication Date(Web):30 Jan 2012
DOI:10.1039/C2CC16744A
Based on photocrosslinkable PEGDMA and GelMA hydrogels, two “bottom-up” approaches (“circle-and-cross” and “layer-by-layer”) were successfully developed to construct osteon-like structures with microchannel networks. Significantly, the “layer-by-layer” approach employing the GelMA hydrogel with a higher biocompatibility was more favorable for building biomimetic osteon.
Co-reporter:Yajun Tang, Jing Sun, Hongsong Fan, Xingdong Zhang
Carbohydrate Polymers 2012 Volume 88(Issue 1) pp:46-53
Publication Date(Web):17 March 2012
DOI:10.1016/j.carbpol.2011.11.058
Gellan gum is a candidate material for cartilage tissue engineering, but its application is limited by the high gelation (Coutinho et al., 2010) temperature and lack of mechanical strength. In this study, oxidized gellan gum was prepared and mixed with carboxymethyl chitosan to form a double-network complex hydrogel with significantly improved gelation temperature (Tgelation) and mechanical properties. The Tgelation was lowered from 42 °C to below physiological temperature by oxidation, and further reduced by complexing with carboxymethyl chitosan. The complex hydrogel showed an increased compressive modulus of 278 kPa, and an ability to return to the original shape after release of the compressive load. In vitro chondrocytes encapsulation and proliferation experiments found that the complex hydrogel significantly enhanced the viability of the cells. These results suggest that, the complex gel of gellan gum and carboxymethyl chitosan is a promising material for cartilage tissue engineering.
Co-reporter:Jing Sun, Wenqian Xiao, Yajun Tang, Kuifeng Li and Hongsong Fan
Soft Matter 2012 vol. 8(Issue 8) pp:2398-2404
Publication Date(Web):12 Jan 2012
DOI:10.1039/C2SM06869A
Hydrogels hold great promise for bone tissue engineering but their application is greatly limited by their low cell affinity and poor mechanical properties, as well as limited cell spreading ability for anchorage dependent cells such as osteoblasts. In this study, a series of hydrogels based on an interpenetrating polymer network (IPN) of methacrylated alginate (MAA) and collagen were developed to support pre-osteoblast spreading and proliferation as well as osteogenic differentiation. Compared to the pure MAA hydrogel, these hydrogels demonstrated higher mechanical moduli, lower swelling ratios and denser network structures. Moreover, the properties could be fine-tuned by altering the ratio of collagen and alginate. MC3T3-E1 cells in IPN hydrogels exhibited a rapid proliferation and spread gradually with prolonged culture time, and their osteogenic differentiation was greatly facilitated. While for the MAA hydrogel, the cells remained in a rounded morphology with bad osteogenic differentiation. These results should provide collagen–MAA IPN hydrogels as potential three-dimensional scaffolds for bone tissue engineering.
Co-reporter:Huaifa Zhang, Ming Liu, Hongsong Fan, and Xingdong Zhang
Crystal Growth & Design 2012 Volume 12(Issue 5) pp:2204-2212
Publication Date(Web):March 21, 2012
DOI:10.1021/cg200917y
The effects of poly(ethylene glycol) (PEG) molecular weights on nano hydroxyapatite (n-HA) crystal growth were studied, and a possible mechanism was proposed. n-HA crystals were synthesized in the presence of PEG with different molecular weights via hydrothermal method. Transmission electron microscopy (TEM) analysis showed that the presence of PEG increased the size of n-HA crystals; PEG with larger molecular weights produced larger n-HA crystals. High-resolution TEM observation indicated that all of the n-HA crystals tended to grow along the ⟨002⟩ axis. X-ray diffraction patterns showed that all of the samples consisted of only the HA phase. Besides, PEG increased the crystallinity of n-HA crystals, and this effect was more significant for PEGs with larger molecular weights. Fourier transform infrared results further revealed that all of the crystals were carbonated HA. Thermogravimetry/differential scanning calorimetry analysis detected PEG residues on n-HA particles. To thoroughly study the modulating mechanism of PEGs on n-HA crystal growth, n-HA samples heat-treated for various times were prepared in the presence of PEG20000, and a possible mechanism in which PEG modulated the growth of n-HA crystals was discussed.
Co-reporter:Huaifa Zhang, Ming Liu, Hongsong Fan, Xingdong Zhang
Materials Letters 2012 Volume 75() pp:26-28
Publication Date(Web):15 May 2012
DOI:10.1016/j.matlet.2012.01.110
A simple and efficient method to prepare carbonated nano hydroxyapatite (n-CHAp) powders with good dispersivity was developed. n-CHAp was synthesized using chemical precipitation method assisted by poly(ethylene glycol) (PEG), the PEG additive and reaction byproduct were excluded through calcination conveniently. The products were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), transmission electron microscope (TEM) and dynamic lighting scattering (DLS), respectively. The results show that PEG can promote HAp formation, modulate the particle morphology and size, and effectively reduce the aggregation of n-CHAp powders. Both PEG and byproduct NH4NO3 can be removed through calcination.Highlights► We developed an efficient way to prepare dispersive nano hydroxyapatite (n-HAp). ► Poly(ethylene glycol) (PEG) was used to prevent the nano particles aggregating. ► PEG improved the dispersivity of n-HAp powders and changed n-HAp morphology. ► This method is a promising candidate to prepare dispersive n-HAp in large scale.
Co-reporter:X. D. Zhu;H.J. Zhang;D. X. Li;H. S. Fan;X. D. Zhang
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2012 Volume 100B( Issue 2) pp:516-523
Publication Date(Web):
DOI:10.1002/jbm.b.31978
Abstract
Currently, nanobioceramics have received much attention due to their potentially high biological performance. In the present study, the interactions between proteins and two types of hydroxyapatite (HA) ceramic particles with distinct microstructures were studied in vitro. Protein adsorption on the microwave sintered and conventionally sintered HA ceramic particles (named as HAMS and HACS, respectively) were carried out in simulated body fluid (SBF) containing model proteins or rat serum and then subjected to protein quantitative evaluation, SDS-PAGE, and Western blotting analysis. The ceramic particles were characterized by nitrogen sorption, Hg penetration, zeta potential, and solubility analysis. It was found that HAMS with nanosized crystallites had greater specific surface area and pore volume and wider pore size distribution ranging from 0.02 to 2 μm than HACS. Although bovine serum albumin and lysozyme have different electrical properties in SBF, both the model proteins showed higher adsorption amounts per gram solid on HAMS than HACS, as could be ascribed to the contribution of the micropores structure of HAMS. Similarly, HAMS adsorbed more serum proteins per gram solid than HACS when incubating in rat serum, and here the surfaces of both particles were almost completely covered by serum proteins, leading to almost the same protein adsorption amounts per unit area solid of HAMS and HACS. SDS-PAGE patterns proved that HA ceramic particles had different binding capacities for different serum proteins and was not highly dependent on the concentrations of the competing protein components present in rat serum. Western blotting analysis confirmed the enhanced adsorption of fibronectin and vitronectin on HAMS, indicating that HAMS might have better bioactivity than HACS. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 516–523, 2012.
Co-reporter:Ling Zhang, Kuifeng Li, Wenqian Xiao, Li Zheng, Yumei Xiao, Hongsong Fan, Xingdong Zhang
Carbohydrate Polymers 2011 Volume 84(Issue 1) pp:118-125
Publication Date(Web):11 February 2011
DOI:10.1016/j.carbpol.2010.11.009
Ideal scaffolds for tissue engineering should mimic natural extracellular matrix (ECM) as much as possible. The aim of this study was to develop a biomimetic hydrogel scaffold with good operability and stability by collagen self-assembly. To improve physical and chemical performances, the hydrogels were crosslinked with different concentrations of genipin using gel-crosslinking method. Morphology, crosslinking index, and content of glycosaminoglycans of the hydrogel scaffolds were characterized. The potential of the hydrogels as cartilage tissue engineering scaffolds was evaluated by compression test, swelling measurement, in vitro degradation assay, and biocompatibility study in vitro. Results showed that hydrogel scaffold crosslinked with 0.75 mM genipin exhibited balanced optimal properties, and excellent cellular compatibility. Since gelation was temperature sensitive and crosslink occurred under mild conditions, the hydrogel scaffold may be well suited as a carrier for chondrocytes transplantation or as cartilage tissue engineering scaffolds.
Co-reporter:Tun Yuan;Kuifeng Li;Likun Guo;Xingdong Zhang
Journal of Biomedical Materials Research Part A 2011 Volume 98A( Issue 3) pp:332-341
Publication Date(Web):
DOI:10.1002/jbm.a.33121
Abstract
Influence of the structures of some collagen scaffolds on immunological properties of the seeded allogeneic mesenchymal stem cells (MSCs) was studied in this article. Hydrogels, sponge, and membrane were prepared from type-I collagen. These scaffolds were seeded with neonatal rabbit MSCs and cultured for different periods. Changes of the immunological properties associated with different scaffolds were analyzed and compared. It was found that the expression of major histocompatibility complex (MHC) class I and II molecules on MSCs increased gradually in all scaffolds, but the least increment was recorded in hydrogels. Mixed lymphocyte reactions (MLR) showed that the MSC-hydrogel constructs invoked considerably low allogeneic lymphocytes proliferation. Even in presence of interferon-γ (IFN-γ), the hydrogels with higher concentration gave comparatively lower increment of MHC-II expression and allogeneic lymphocytes proliferation. These results suggest that different scaffold structures may provide different microenvironments and extents of isolation from the host immune system for the seed cells, thereby affecting their immunological properties. Therefore, scaffold structures may modulate the immunological properties of tissue-engineered cartilage with allogeneic cells. Hydrogels, especially which were prepared from higher collagen concentrations, were found to be a promising scaffold structure, from the perspective of avoiding severe immune rejection. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 2011.
Co-reporter:Tun Yuan, Hongrong Luo, Jing Tan, Hongsong Fan, Xingdong Zhang
Biomaterials 2011 32(26) pp: 6017-6024
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.04.041
Co-reporter:X.D. Zhu, H.J. Zhang, H.S. Fan, Wei Li, X.D. Zhang
Acta Biomaterialia 2010 Volume 6(Issue 4) pp:1536-1541
Publication Date(Web):April 2010
DOI:10.1016/j.actbio.2009.10.032
Abstract
The biological performance of biomaterials is strongly influenced by their protein adsorption characteristics, which are related to the structures and properties of both the biomaterial and the protein. In the present study two groups of hydroxyapatite (HA) and biphasic calcium phosphate (BCP) ceramic powders were fabricated by different drying processes. The roles of the phase composition and microstructure of the powders in the adsorption of various model proteins were evaluated. The experimental results showed that BCP always had a higher ability to adsorb fibrinogen, insulin or type I collagen (Col-I) than HA. The microporosity and micropore size of the CaP particles also had a strong impact on their protein adsorption characteristics. HA and BCP particles with higher microporosities and/or more micropores >20 nm in diameter could adsorb more fibrinogen or insulin. However, amounts of adsorbed Col-I were largely unaffected by the microstructure of HA and BCP particles.
Co-reporter:Ling Zhang;Yumei Xiao;Bo Jiang;Xingdong Zhang
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2010 Volume 92B( Issue 2) pp:307-316
Publication Date(Web):
DOI:10.1002/jbm.b.31516
Abstract
Collagen and hydrazide-functionalized hyaluronic acid derivatives were hybridized by gelating and genipin crosslinking to form composite hydrogel. The study contributed to the understanding of the effects of adipic dihydrazide modification on the physicochemical and biological properties of the collagen/hyaluronic acid scaffold. The investigation included morphology observation, mechanical measurement, swelling evaluation, and collagenase degradation. The results revealed that the stability of composites was increased through adipic dihydrazide modification and genipin crosslinking. The improved biocompatibility and retention of hyaluronic acid made the composite material more favorable to chondrocytes growing, suggesting the prepared scaffold might be high potential for chondrogenesis. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010
Co-reporter:Chaoyong Zhao;Xiangdong Zhu;Kailu Liang;Jietao Ding;Zhou Xiang;Xingdong Zhang
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2010 Volume 95B( Issue 2) pp:387-396
Publication Date(Web):
DOI:10.1002/jbm.b.31728
Abstract
In this study, a slurry foaming method was developed to fabricate porous titanium, and two different surface treatments were applied to investigate their effects on the osteoinduction of the implants. Three types of implants, that was porous titanium with no treatment, with chemical-thermal treatment (CTPT), and with acid-alkali treatment (AAPT), were implanted in the dorsal muscles of adult dogs for 3 and 5 months. After implantation for 3 months, new bone was only found in the inner pores of AAPT by histological analysis and field emission scanning electron microscopy observation. After implantation for 5 months, new bone was also found in CTPT, but it was absent in AAPT. This study not only confirmed that porous titanium with appropriate surface treatments could possess osteoinduction but also showed that its osteoinductive potential was tightly related to the surface treatment. As a simpler method, acid-alkali treatment could endow porous titanium with faster osteoinduction, and AAPT might have potential in clinical application. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.
Co-reporter:C.Y. Zhao, X.D. Zhu, T. Yuan, H.S. Fan, X.D. Zhang
Materials Science and Engineering: C 2010 30(1) pp: 98-104
Publication Date(Web):
DOI:10.1016/j.msec.2009.09.004
Co-reporter:Dan Kai;Dongxiao Li;Xiangdong Zhu
Journal of Materials Science: Materials in Medicine 2009 Volume 20( Issue 8) pp:1595-1602
Publication Date(Web):2009 August
DOI:10.1007/s10856-009-3728-y
An injectable calcium phosphate cement (CPC) with porous structure and excellent anti-washout ability was developed in the study. Citric acid and sodium bicarbonate were added into the CPC powder consisting of tetracalcium phosphate (TTCP) and dicalcium phosphate dihydrate (DCPD) to form macro-pores, then different concentrations of sodium hyaluronate (NaHA) solution, as liquid phase, was added into the cement to investigate its effect on CPC’s performance. The prepared CPCs were tested on workability (injectable time and setting time), mechanical strength, as well as anti-washout ability. The experimental results showed that addition of NaHA not only enhanced the anti-washout ability of the CPC dramatically but also improve its other properties. When NaHA concentration was 0.6 wt%, the injectable time elongated to 15.7 ± 0.6 min, the initial and final setting times were respectively shorten to 18.3 ± 1.2 and 58.7 ± 2.1 min, and the compressive strength were increased to 18.78 ± 1.83 MPa. On the other hand, Addition of NaHA showed little effect on porous structure of the CPC and enhanced its bioactivity obviously, which was confirmed by the apatite formation on its surface after immersion in simulated body fluid (SBF). In conclusion, as an in situ shaped injectable biomaterials, the CPC with appropriate addition of NaHA would notably improve its performance and might be used in minimal invasive surgery for bone repair or reconstruction.
Co-reporter:B. W. Kunkel
Science 1919 Vol 50(1291) pp:305-306
Publication Date(Web):26 Sep 1919
DOI:10.1126/science.50.1291.305
Co-reporter:Huaifa Zhang, Fangzhu Qing, Huan Zhao, Hongsong Fan, Ming Liu and Xingdong Zhang
Journal of Materials Chemistry A 2017 - vol. 5(Issue 6) pp:NaN1217-1217
Publication Date(Web):2016/12/30
DOI:10.1039/C6TB01401A
Nano hydroxyapatite particles (n-HA) have been reported to promote osteogenic activities of bone-related cells, while inhibiting tumor cell growth, and the biological effects of n-HA are related with the particle size, dose, culture time and cell type. In this work, we prepared n-HA with a strictly controlled rod-like shape and adjustable sizes without any surface chemical contaminations. Using the prepared n-HA, we investigated the size and dose effect of the nano particles on pre-osteoblasts for up to 7 days. We probed cell proliferation and gene expression in the presence of n-HA, the cellular uptake pathways of n-HA particles, as well as the extracellular and intracellular [Ca2+] ([Ca2+]i) changes caused by the particles, in order to get a better understanding of the biological effects of n-HA of various sizes. The n-HA exhibited size- and dose-dependent impacts on MC3T3-E1 proliferation, intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential, and osteogenic gene expression. 40 nm n-HA caused the slowest MC3T3-E1 growth, the highest intracellular ROS concentration, the largest mitochondrial membrane potential loss and the lowest level of osteogenic gene expression among the samples. The cytotoxicity of 40 nm n-HA increased with the dose and culture time. 70 nm n-HA showed beneficial effects on MC3T3-E1 growth, but the positive effect disappeared at the highest concentration on day 7. 100 nm n-HA promoted cell growth and the promoting effect increased with the dose. Cells cultured with 100 nm n-HA expressed the highest level of osteogenic gene expression among the experimental groups. We discovered that the presence of n-HA increased [Ca2+]i but did not elevate extracellular [Ca2+]. The [Ca2+]i increased as the n-HA size decreased. We also found that n-HA may enter cells through two pathways and that the amount of engulfed particles depended on the particle size. The internalized n-HA particles located in the cytosol, endosomes, lysosomes and nuclei. The particles dissolved in lysosomes and raised [Ca2+]i, which correlated with the cell death and osteogenic gene expression. In conclusion, the particle size, dose, and culture time influenced the biological effects of n-HA on ME3T3-E1 cells, probably by changing the [Ca2+]i in the cells instead of the extracellular [Ca2+].
Co-reporter:Chaoyong Zhao, Hongfang Zhang, Bing Cai, Guanglin Wang, Hongsong Fan and Xingdong Zhang
Biomaterials Science (2013-Present) 2013 - vol. 1(Issue 7) pp:NaN710-710
Publication Date(Web):2013/03/27
DOI:10.1039/C3BM00199G
In this study, a porous PLGA/Ti biphasic scaffold was prepared and its potential to repair osteochondral defects was evaluated. The microstructure and mechanical properties of porous PLGA and porous Ti and their interface were characterized. The as-prepared biphasic scaffolds were implanted into rabbit knees for 1 and 3 months (PLGA/Ti group), and the porous PLGA (PLGA group) or empty defect (Untreated group) was also used. The results showed that both porous PLGA and porous Ti had an interconnected porous structure. The mechanical strength of porous PLGA and porous Ti was similar to that of cartilage and subchondral bone, respectively. The interface analysis revealed that the as-prepared biphasic scaffold had good overall integrity and interface stability. The gross observation and histological evaluation of specimens showed that hyaline-like cartilage filled the defects to a certain extent at 3 months for both PLGA/Ti and PLGA groups while the defects remained in an untreated group. In the PLGA/Ti group, better cartilage and subchondral bone repair was observed, and quantitative macroscopic and histological score evaluations confirmed this result, indicating that the porous biphasic PLGA/Ti scaffold had good biocompatibility and the best osteochondral defect repair ability in this study. The as-prepared porous biphasic scaffold showed the potential to be used in osteochondral tissue engineering for osteochondral defect repair.
Co-reporter:Dongli Jiang, Huan Zhao, You Yang, Yuda Zhu, Xiaoqin Chen, Jing Sun, Kui Yu, Hongsong Fan and Xingdong Zhang
Journal of Materials Chemistry A 2017 - vol. 5(Issue 20) pp:NaN3757-3757
Publication Date(Web):2017/04/18
DOI:10.1039/C6TB03184F
Defect-related fluorescent HAp materials, which require no toxic metal ions or photobleaching fluorescent organic dyes, are expected to be excellent fluorescent probes in biological fields. However, the luminescent mechanism is poorly understood, making it difficult to adjust their emission performance for better applications in bioimaging. Herein, a novel luminescent mechanism for defect-related HAp fluorescent materials obtained from a typical hydrothermal process was revealed. N-Rich carbon dots (CDs), rather than the reported CO2˙−, were confirmed as the luminescence centers responsible for self-activated luminescence. The mode in which the N-rich CDs and HAp host combined might be through CDs (mainly polymer clusters and/or molecular fluorophores constituents) becoming trapped in the HAp crystal structure. This study should inspire the design of fluorescent HAp materials with tunable fluorescence emissions due to the diverse synthetic methods and tunable fluorescence emission of CDs.
Co-reporter:Yicong Zuo, Wenqian Xiao, Xiaoqin Chen, Yajun Tang, Hongrong Luo and Hongsong Fan
Chemical Communications 2012 - vol. 48(Issue 26) pp:NaN3172-3172
Publication Date(Web):2012/01/30
DOI:10.1039/C2CC16744A
Based on photocrosslinkable PEGDMA and GelMA hydrogels, two “bottom-up” approaches (“circle-and-cross” and “layer-by-layer”) were successfully developed to construct osteon-like structures with microchannel networks. Significantly, the “layer-by-layer” approach employing the GelMA hydrogel with a higher biocompatibility was more favorable for building biomimetic osteon.
Co-reporter:Huan Zhao, Yu-Da Zhu, Jing Sun, Dan Wei, Ke-Feng Wang, Ming Liu, Hong-Song Fan and Xing-Dong Zhang
Chemical Communications 2014 - vol. 50(Issue 83) pp:NaN12522-12522
Publication Date(Web):2014/08/28
DOI:10.1039/C4CC05088F
Hollow hydroxyapatite nanospheres were prepared by a two-phase approach by controlling nucleation and crystal growth processes. The cavities of hollow HA provide potential applications as new kinds of containers for carrying, filling in, or encapsulating other materials, thus constructing a multifunctional system with good biocompatibility.
Co-reporter:Meiling Zhong, Jing Sun, Dan Wei, Yuda Zhu, Likun Guo, Qingrong Wei, Hongsong Fan and Xingdong Zhang
Journal of Materials Chemistry A 2014 - vol. 2(Issue 38) pp:NaN6610-6610
Publication Date(Web):2014/08/07
DOI:10.1039/C4TB00887A
Hydrogels hold great promise for tissue engineering and as cell delivery vehicles, but their application is greatly limited by the mass depletion of cells after encapsulation due to their low cell affinity and high cell constraints. In this study, using human osteoblast-like cells (MG63) as a model for anchorage-dependent cells (ADCs), alginate hydrogels incorporated with collagen microcarriers (MCs) and collagenase (GCE) were constructed to promote the cellular functional establishment. In this system, the cell-laden microcarriers as cellular ‘anchors’ provided a cell-affinitive interface between cells and hydrogels, while the collagenase promoted the degradation of collagen microspheres and thus provided adequate room for cell spreading and migration. Compared to the pure alginate hydrogel (Gel), the alginate hydrogel/microcarrier composite (GC) improved initial cell spreading by supplying a cell adhesive interface, while GCE with both microcarriers and collagenase exhibited much better cell spreading, proliferation and differentiation, which is attributed to the sustainable supply of both a cell adhesive interface and cell spreading room. The composites showed potential as an injectable vehicle for the conveyance of ADCs and tissue engineering.
Co-reporter:Dan Wei, Wenqian Xiao, Jing Sun, Meiling Zhong, Likun Guo, Hongsong Fan and Xingdong Zhang
Journal of Materials Chemistry A 2015 - vol. 3(Issue 14) pp:NaN2763-2763
Publication Date(Web):2015/02/13
DOI:10.1039/C5TB00129C
Surface tension driven assembly is a simple and rapid strategy in “modular” tissue engineering to fabricate three-dimensional (3D) structures with predefined geometrical and biological features. Besides the biocompatibility for encapsulated cells, the mechanical and hydrophilic properties of the microgel are the utmost two factors for assembly and structure preservation. Herein, we developed a new composite hydrogel based on photocrosslinkable methacrylated gelatin (GelMA) and methacrylated alginate (AlgMA) for modular tissue engineering assembly. Based on the high cellular bioactivity of GelMA, inflexible AlgMA with a large number of hydrophilic groups was introduced to optimize the hydrogel assembly performance. The results revealed that the mechanical stiffness, swelling ratio and hydrophilicity were improved greatly, and the nutrient permeability as well as the cellular activity remained at a relatively high level simultaneously. The enhanced stiffness and hydrophilicity were helpful for the surface tension driven assembly, and the high nutrient permeability was conducive to the activity of encapsulated cells. Moreover, microgels with different shapes were fabricated, and microengineered complex structures constructed with spatial organized cell distribution and specific functions, such as osteon-like structure containing both osteogenic and vascularized area, were successfully generated by “Lock and key” and “Concentric double-ring” assemblies. The composite hydrogel provides a potential candidate material for modular tissue engineering.
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