| Articular cartilage plays a vital role in joint stability maintenance and normal activities, having functional roles in lubrication, reduced friction and pain.However, articular cartilage would not have a capacity of self-healing, because of the lack of vascular and nerve composition, which is quite likely to resulting into fibrocartilage and osteoarthritis(OA).At present,autologous chondrocyte implantation(ACI) and marrow stimulation techniques(MST) are two commonly used methods for the treatment of cartilage diseases in clinical, of which the aim is to cartilage regeneration. But the actual effects is still far away from satisfaction, and can not fundamentally figure out the challenge of cartilage repair.As the limitation of large number of cultured cells, it is quite difficult for patients to carry out the ACI surgy. MST is easily controlled,however, few mesenchymal stromal cells could fill with the defected, and blood clots are also easily formed at the surface of articular groove.Finally the defects would be formed by scar or filled with fibrillar tissue, leading to fibrocartilage. Here in this study, mechano growth factor(MGF), one of the splicing isoforms of insulin growth factor 1, was demonstrated to promote transforming growth factor β3(TGF-β3) induced chondrogenesis of bone marrow mesenchymal stem cells(BMSCs), along with repression of fibrillar formation. In addition, MGF could increased the migration of BMSCs in vitro. In this research, MGF and TGF-β3 were successfully incorperated into silk fibroin scaffolds and sustained release in vivo. When subcutaneously implanted, MGF and TGF-β3 functionalizd silk fibroin(STM) scaffolds could recruit more stem cells into the scaffold, as evidenced by cell isolation, immunofluorescence staining and flow cytometry characterism at 7 days post surgy.When subcutaneously implanted for 2 months, MGF enhanced the chondrogenesis of MSCs and increased the cartilage matrix in STM scaffolds, as evidenced by Safrain O staining. Meanwhile, MGF reduced the myofiber formation, as distinguish from Masson`s trichrome staining.When subjected to caritilage defect in rabbit model, none of chondrocytes and cartilage matrix was observed in the untreated silk fibroin scaffolds(SF), leaving poor integration of scaffolds and native tissue. TGF-β3 treated silk fibroin scaffolds(ST) showed improving regeneration of cartilage at the edges, but the central area of the defects was filled with great amount of fibrillar tissues, marked with collagen I in the patella groove. STM scaffolds promote total regeneration of articular cartilage, supported by smooth neotissue consisted of large number of aggrecan, normal expression of collagen II and little expression of collagen I. Repair results of STM scaffolds were as much similar as to the native cartilage, indicating the great potency of STM scaffolds used for cartilage regeneration. In a word, the conclusions of this research were summaried as following: ①MGF could significantly increased migration of BMSCsin vitro.②MGF promote TGF-β3 induced chondrogenesis of BMSCs, along with repression of fibrillar formation. ③STM scaffolds could recruit more MSCs infiltration and enhanced cartilage matrix synthesis and chondrogenic differentiation under subcutaneous implantation for long term investigation. ④STM scaffolds couldenhanced endogenous stem cell recruitment and infiltration in articular cartilage defects, facilitatingin situ articular cartilage regenerationfor long term study, thus providing a novelstrategy for cartilage repair. |
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