Optimization of chondrogenic differentiation of human adipose tissue-derived stem cells on poly(L-lactide-co-ε-caprolactone) scaffolds

Abstract

Mechanical stimuli should enhance cartilaginous tissue formation in elastic mechano-active poly(L-lactide- co-ε-caprolactone) (PLCL) scaffolds similar to what is observed in the body. The conditions for stem cell differentiation are also crucial for cartilage tissue engineering. Here, we investigate cartilaginous tissue formation of human adipose-tissue derived stem cells (hASCs)/hybrid scaffold constructs with fibrin gel and PLCL scaffolds. For this, hASCs were mixed with 1% or 5% fibrin gel and were subsequently seeded onto the PLCL scaffolds. Next, chondrogenesis was induced in vitro in the constructs with chondrogenic medium for 14 or 21 days to determine the optimal concentration of fibrin gel and pre-conditioning period. After pre-conditioning, the constructs were subcutaneously implanted in nude mice for up to 8 weeks. The constructs grown in 5% fibrin gel and induced for 21 days or 1% fibrin gel and induced for 14 days showed higher depositions of cartilage-specific extracellular matrix (ECM) components compare to the constructs in 5% fibrin gels that were induced for 14 days or 1% fibrin gels induced for 21 days. These results indicated that the constructs maintained in dense hydrogels need longer pre-conditioning periods for chondrogenesis. Consequently, the hybrid constructs in which chondrogenesis is appropriately induced in vitro could be used to engineer cartilage.