Sarsenova Madina, Raimagambetov Yerik, Issabekova Assel, Karzhauov Miras, Kudaibergen Gulshakhar, Akhmetkarimova Zhanar, Batpen Arman, Ramankulov Yerlan, Ogay Vyacheslav
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.
Polymers (Basel). 2022 Dec 7;14(24):5343. doi: 10.3390/polym14245343.
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.
软骨及骨软骨缺损的再生仍然是整形外科中最具挑战性的临床问题之一。目前，基于在水凝胶支架中递送合适的生长因子和间充质干细胞（MSCs）的组织工程技术被认为是骨软骨缺损再生最有前景的治疗策略。在本研究中，我们制备了一种肝素共轭纤维蛋白（HCF）水凝胶，其包含滑膜来源的间充质干细胞（SDMSCs）、转化生长因子-β1（TGF-β1）和骨形态发生蛋白-4（BMP-4），用于修复兔模型中的骨软骨缺损。体外研究表明，HCF水凝胶具有良好的生物相容性、缓慢的降解速率以及在4周内持续释放TGF-β1和BMP-4。宏观和组织学评估显示，与单独含有SDMSCs或生长因子的水凝胶相比，植入含有SDMSCs、TGF-β1和BMP-4的HCF水凝胶在12周内显著增强了骨软骨缺损处透明软骨和软骨下骨板的再生。因此，这些数据表明，在HCF水凝胶中联合递送SDMSCs与TGF-β1和BMP-4可能协同增强膝关节骨软骨缺损修复的治疗效果。
