Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM ligands and controls their osteogenic differentiation

The osteogenic potential of mesenchymal stem cells (MSCs) cultured on poly(lactide‐co‐glycolide) (PLGA) or poly(caprolactone) (PCL), two widely used polymeric biomaterials that have been reported to differentially support osteogenic differentiation, was compared in these studies. Here we report that MSCs cultured in 3‐D PLGA scaffolds for up to 5 weeks significantly upregulate osteocalcin gene expression levels. By contrast, osteocalcin expression was markedly downregulated in 3‐D PCL‐based constructs over the same time course. We hypothesized that differential adsorption of extracellular matrix (ECM) proteins present in serum‐containing culture medium and subsequent differences in integrin‐mediated adhesion are responsible for these differences, and tested this hypothesis using thin (2‐D) polymeric films. Supporting this hypothesis, significant amounts of fibronectin and vitronectin deposited onto both materials in serum‐containing osteogenic media, with type‐I collagen present in lower amounts. Adhesion‐blocking studies revealed that MSCs adhere to PCL primarily via vitronectin, while type‐I collagen mediates their attachment to PLGA. These adhesive mechanisms correlated with higher levels of alkaline phosphatase (ALP) activity after 2 weeks of monolayer culture on PLGA versus PCL. These data suggest that the initial adhesion of MSCs to PLGA via type‐I collagen fosters osteogenesis while adhesion to PCL via vitronectin does not, and stress the need for an improved molecular understanding of cell–ECM interactions in stem cell‐based therapies. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006