Controlled release of transforming growth factor-?3 from cartilage-extra-cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue-derived stem cells.

Abstract

Abstract: The objective of this study was to develop a scaffold derived from cartilaginous extracellular matrix (ECM) that could be used as a growth factor delivery system to promote chondrogenesis of stem cells. Dehyd rothermal crosslinked scaffolds were fabricated using a slurry of homogenized porcine articular cartilage, which were then seeded with human infrapatellar fat pad derived stem cells (FPSCs). It was found that these ECM derived scaffolds promoted superior c hondrogenesis of FPSCs when the constructs were additionally stimulated with transforming growth factor (TGF) - β3. Cell mediated contraction of the scaffold was observed, which could be limited by the additional use of 1 - Ethyl - 3 - 3dimethyl aminopropyl carbod iimide (EDAC) crosslinking without suppressing cartilage specific matrix accumulation within the construct. To further validate the utility of the ECM derived scaffold, we next compared its chondro - permissive properties to a biomimetic collagen - hyaluronic acid (HA) scaffold optimized for cartilage tissue engineering (TE) applications. The cartilage ECM derived scaffold supported at least comparable chondrogenesis to the collagen - HA scaffold, underwent less contraction and retained a greater proportion of sy nthesised sulphated glycosaminoglycans (sGAGs). Having developed a promising scaffold for TE, with superior chondrogenesis observed in the presence of exogenously supplied TGF - β3, the final phase of the study explored whether this scaffold could be used as a TGF - β3 delivery system to promote chondrogenesis of FPSCs. It was found that the majority of TGF - β3 that was loaded onto the scaffold was released in a controlled manner over the first 10 days of culture, with comparable long - term chondrogenesis observe d in these TGF - β3 loaded constructs compared to scaffolds where the TGF - β3 was continuously added to the media. The results of this study support the use of cartilage ECM derived scaffolds as a growth factor delivery system for use in articular cartilage r egeneration