Regeneration of Osteochondral Defects by Combined Delivery of Synovium-Derived Mesenchymal Stem Cells, TGF-β1 and BMP-4 in Heparin-Conjugated Fibrin Hydrogel

Sarsenova M. Raimagambetov Y. Issabekova A. Karzhauov M. Kudaibergen G. Akhmetkarimova Z. Batpen A. Ramankulov Y. Ogay V.
December 2022 MDPI

Polymers
2022 #14 Issue 24

The regeneration of cartilage and osteochondral defects remains one of the most challenging clinical problems in orthopedic surgery. Currently, tissue-engineering techniques based on the delivery of appropriate growth factors and mesenchymal stem cells (MSCs) in hydrogel scaffolds are considered as the most promising therapeutic strategy for osteochondral defects regeneration. In this study, we fabricated a heparin-conjugated fibrin (HCF) hydrogel with synovium-derived mesenchymal stem cells (SDMSCs), transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-4 (BMP-4) to repair osteochondral defects in a rabbit model. An in vitro study showed that HCF hydrogel exhibited good biocompatibility, a slow degradation rate and sustained release of TGF-β1 and BMP-4 over 4 weeks. Macroscopic and histological evaluations revealed that implantation of HCF hydrogel with SDMSCs, TGF-β1 and BMP-4 significantly enhanced the regeneration of hyaline cartilage and the subchondral bone plate in osteochondral defects within 12 weeks compared to hydrogels with SDMSCs or growth factors alone. Thus, these data suggest that combined delivery of SDMSCs with TGF-β1 and BMP-4 in HCF hydrogel may synergistically enhance the therapeutic efficacy of osteochondral defect repair of the knee joints.

BMP-4 , controlled release , heparin-conjugated fibrin hydrogel , osteochondral defect , regeneration , synovium-derived mesenchymal stem cells , TGF-β1

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Stem Cell Laboratory, National Center for Biotechnology, Astana, 010000, Kazakhstan
National Scientific Center of Traumatology and Orthopedics Named after Academician N.D. Batpenov, Astana, 010000, Kazakhstan
School of Science and Humanities, Nazarbayev University, Astana, 010000, Kazakhstan

Stem Cell Laboratory
National Scientific Center of Traumatology and Orthopedics Named after Academician N.D. Batpenov
School of Science and Humanities

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