The chondrogenic differentiation of BMSCs in collagen hydrogels and the effect of MMPs among cell-material interactions

Abstract

The purpose of this study was to investigate the influence of the advanced structure of collagen on the chondrogenic differentiation of BMSCs encapsulated in collagen hydrogels, with an emphasis on MMPs which might affect the cell-material interactions. Collagen and gelatin-based hydrogels with comparable physicochemical properties but mainly distinctive in molecular structure were prepared and further utilized to load BMSCs to study the chondrogenesis. The detection results of MMPs in hydrogels with and without TIMP at both gene and protein levels suggested that MMPs were involved in cell recognition, adhesion, migration, proliferation and further remodeling of cell microenvironment. The chondrogenic gene detection, histological observation and extracellular matrix analysis indicated that the BMSCs were well differentiated into chondrocytes and maintained the phenotypes in collagen hydrogels (C group) which preserved the native structures, comparing with those results acquired from gelatin hydrogels (G group). Finally, the expression of several integrin subunits was investigated to analyze the connection of these cell membrane surface proteins and microenvironment remodeled by MMPs in collagen and gelatin hydrogels. The conclusion was drawn that the advanced structure of collagen affected the chondrogenesis of BMSCs via the cell-material interactions, among which MMPs were one of the major factors crucial to form appropriate microenvironment to modulate the BMSCs fate. Graphical abstract