Fibrin Glues in Combination with Mesenchymal Stem Cells to Develop a Tissue-Engineered Cartilage Substitute

Abstract

Damage of cartilage due to traumatic or pathological conditions results in disability and severe pain. Regenerative medicine, using tissue engineering-based constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a promising approach for restoration of structure and function. Fresh fibrin (FG) and platelet-rich fibrin (PR-FG) glues produced by the CryoSeal(®) FS System, in combination with human bone marrow-derived mesenchymal stem cells (BM-hMSCs), were evaluated in this study. We additionally tested the incorporation of heparin-based delivery system (HBDS) into these scaffolds to immobilize endogenous growth factors as well as exogenous transforming growth factor-β(2). Strongly, CD90+ and CD105+ hMSCs were encapsulated into FG and PR-FG with and without HBDS. Encapsulation of hMSCs in PR-FG led to increased expression of collagen II gene at 2.5 weeks; however, no difference was observed between FG and PR-FG at 5 weeks. The incorporation of HBDS prevented the enhancement of collagen II gene expression. BM-hMSCs in FG initially displayed enhanced aggrecan gene expression and increased accumulation of Alcian blue-positive extracellular matrix; incorporation of HBDS into these glues did not improve aggrecan gene expression and extracellular matrix accumulation. The most significant effect on cartilage marker gene expression and accumulation was observed after encapsulation of hMSCs in FG. We conclude that FG is more promising than PR-FG as a scaffold for chondrogenic differentiation of hMSCs; however, immobilization of growth factors inside these fibrin scaffolds with the HBDS system has a negative impact on this process. In addition, BM-hMSCs are valid and potentially superior alternatives to chondrocytes for tissue engineering of articular cartilage.