Preparation of Stepwise Adipogenesis-Mimicking ECM-Deposited PLGA-Collagen Hybrid Meshes and Their Influence on Adipogenic Differentiation of hMSCs.

Abstract

Extracellular matrixes (ECMs) play a vital role in controlling cell functions because of their similarity to the in vivo microenvironment. The composition of ECMs is not constant but dynamically remolded during stem cell differentiation and tissue development. Development of three-dimensional (3D) biomimetic ECM scaffolds is desirable for investigation of ECM-cell interactions and tissue engineering applications. Here, 3D ECM scaffolds that mimicked the dynamic ECM remodeling during stepwise adipogenesis of human mesenchymal stem cells (hMSCs) were developed. A biodegradable hybrid mesh of poly-(dl-lactic-co-glycolic acid) and collagen was used as a template for cell culture. hMSCs were cultured in the hybrid mesh, and their adipogenic differentiation was controlled at early, late, and undifferentiated stages. Three types of stepwise 3D ECM hybrid scaffolds were prepared from the cultured cells after decellularization. They are mesenchymal stem cell ECM scaffold (SC-ECM scaffold), early-stage adipogenesis-mimicking ECM scaffold (EA-ECM scaffold), and late-stage adipogenesis-mimicking ECM scaffold (LA-ECM scaffold). The stepwise 3D ECM scaffolds had a different composition that was dependent on the differentiation stage of hMSCs. They also showed a different influence on the adipogenic differentiation of hMSCs. The EA-ECM scaffold promoted, while the SC-ECM and LA-ECM scaffolds inhibited the adipogenic differentiation of hMSCs.