A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration

Meng, Qiong; Man, Zhentao; Dai, Linghui; Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Zhang, Jiying; Fu, Xin; Duan, Xin; Ao, Yingfang

doi:10.1038/srep17802

Cited by 98 publications

(71 citation statements)

References 45 publications

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“…DBM also contains a large amount of BMP and has shown osteoinductive potential in vivo [29]. BMSCs are a promising seed-cell source for bone repair, which can be achieved using micro-fracture surgery [30]. Thus, combining BMSCs with DBM should have a synergistic effect on the treatment of bone defects.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-Mediated Expression of BMP-2 and BFGF in Bone Marrow Mesenchymal Stem Cells Combined with Demineralized Bone Matrix For Repair of Femoral Head Osteonecrosis in Beagle Dogs

Peng

Wang²

2017

Cell Physiol Biochem

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Background: This study investigated the effect of using adenovirus-mediated expression of bone morphogenetic protein 2 (Ad-BMP-2) and basic fibroblast growth factor (bFGF) in bone marrow mesenchymal stem cells (BMSCs) in combination with a demineralized bone matrix (DBM) to repair osteonecrosis of the femoral head (ONFH) in Beagle dogs. Methods: A total of 30 Beagle dogs were selected for the isolation of BMSCs, which were cultured and transfected with the recombinant adenovirus vector Ad-BMP2-bFGF-GFP (carrying BMP-2 and bFGF) or a control adenovirus plasmid (encoding green fluorescent protein (Ad-GFP)). The expression of the transfected BMP-2 and bFGF proteins was detected by Western blotting. After transfection, the BMSCs were induced to undergo osteoblastic differentiation. The DBM was prepared to construct a DBM/BMSC complex. Beagle models of canine femoral head defects and necrosis were established and divided into control, DBM, DBM/BMSC, vector Ad-BMP2-bFGF-GFP and Ad-GFP groups. The composite graft was then implanted, and new bone morphology was visualized via X-ray at 3, 6 and 12 weeks after the operation. Hematoxylin and eosin (HE) staining and Masson’s trichrome staining were used to identify new bone formation. Immunohistochemistry was performed to calculate the density of new blood vessels. The compressive and bending strength of the BMSCs was evaluated at 12 weeks after the operation. Results: BMSCs were successfully isolated. The protein expression of BMP-2 and bFGF was significantly higher in the Ad-BMP-2/bFGF group than the normal and Ad-GFP groups. Compared with the control group, at 12 weeks after the operation, the DBM, DBM/BMSC, vector Ad-BMP2-bFGF-GFP and Ad-GFP groups showed a larger area of new bone, higher X-ray scores, greater neovascularization density, and increased compressive and bending strength. The most significant modifications occurred in thevector Ad-BMP2-bFGF-GFP group. Conclusion: The results indicate that the use of Ad-BMP-2/bFGF-modified BMSCs in conjunction with DBM could successfully repair ONFH in a dog model by promoting bone formation and angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Adenovirus-Mediated Expression of BMP-2 and BFGF in Bone Marrow Mesenchymal Stem Cells Combined with Demineralized Bone Matrix For Repair of Femoral Head Osteonecrosis in Beagle Dogs

Peng

Wang²

2017

Cell Physiol Biochem

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“…Hydrogels with highly hydrated polymer networks mimic the native ECM while porous scaffolds provide for superior mechanical properties and mass transport of nutrients and wastes. Many studies have indicated that MSC‐laden hydrogels improved cartilage repair . However, those cell‐laden constructs were lack of mechanical strength.…”

Section: Applications Of Substrate‐derived Spheroids In Tissue Regenementioning

confidence: 99%

Biomaterial Substrate‐Mediated Multicellular Spheroid Formation and Their Applications in Tissue Engineering

Tseng

Wong

Hsieh

et al. 2017

Biotechnology Journal

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Three-dimentional (3D) multicellular aggregates (spheroids), compared to the traditional 2D monolayer cultured cells, are physiologically more similar to the cells in vivo. So far there are various techniques to generate 3D spheroids. Spheroids obtained from different methods have already been applied to regenerative medicine or cancer research. Among the cell spheroids created by different methods, the substrate-derived spheroids and their forming mechanism are unique. This review focuses on the formation of biomaterial substrate-mediated multicellular spheroids and their applications in tissue engineering and tumor models. First, the authors will describe the special chitosan substrate-derived mesenchymal stem cell (MSC) spheroids and their greater regenerative capacities in various tissues. Second, the authors will describe tumor spheroids derived on chitosan and hyaluronan substrates, which serve as a simple in vitro platform to study 3D tumor models or to perform cancer drug screening. Finally, the authors will mention the self-assembly process for substrate-derived multiple cell spheroids (co-spheroids), which may recapitulate the heterotypic cell-cell interaction for co-cultured cells or crosstalk between different types of cells. These unique multicellular mono-spheroids or co-spheroids represent a category of 3D cell culture with advantages of biomimetic cell-cell interaction, better functionalities, and imaging possibilities.

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“…Moreover, 19.7% of the studies evaluated CS in the regeneration of skin [24, 27, 29, 63–71], 14.7% in nervous tissue [30, 72–79], 11.5% in cartilage [32, 81–84, 87, 88], and 3.3% in periodontal [33, 90] structures. The remaining studies involved regeneration of colorectal [26], mammary [89], tympanic membrane [31], and vascular [34] tissues (1.6% each).…”

Section: Resultsmentioning

confidence: 99%

Versatility of Chitosan-Based Biomaterials and Their Use as Scaffolds for Tissue Regeneration

Ribeiro

Vieira

Melo

et al. 2017

The Scientific World Journal

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Chitosan is a naturally occurring polysaccharide obtained from chitin, present in abundance in the exoskeletons of crustaceans and insects. It has aroused great interest as a biomaterial for tissue engineering on account of its biocompatibility and biodegradation and its affinity for biomolecules. A significant number of research groups have investigated the application of chitosan as scaffolds for tissue regeneration. However, there is a wide variability in terms of physicochemical characteristics of chitosan used in some studies and its combinations with other biomaterials, making it difficult to compare results and standardize its properties. The current systematic review of literature on the use of chitosan for tissue regeneration consisted of a study of 478 articles in the PubMed database, which resulted, after applying inclusion criteria, in the selection of 61 catalogued, critically analysed works. The results demonstrated the effectiveness of chitosan-based biomaterials in 93.4% of the studies reviewed, whether or not combined with cells and growth factors, in the regeneration of various types of tissues in animals. However, the absence of clinical studies in humans, the inadequate experimental designs, and the lack of information concerning chitosan's characteristics limit the reproducibility and relevance of studies and the clinical applicability of chitosan.

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A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration

Cited by 98 publications

References 45 publications

Adenovirus-Mediated Expression of BMP-2 and BFGF in Bone Marrow Mesenchymal Stem Cells Combined with Demineralized Bone Matrix For Repair of Femoral Head Osteonecrosis in Beagle Dogs

Adenovirus-Mediated Expression of BMP-2 and BFGF in Bone Marrow Mesenchymal Stem Cells Combined with Demineralized Bone Matrix For Repair of Femoral Head Osteonecrosis in Beagle Dogs

Biomaterial Substrate‐Mediated Multicellular Spheroid Formation and Their Applications in Tissue Engineering

Versatility of Chitosan-Based Biomaterials and Their Use as Scaffolds for Tissue Regeneration

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