Integrin β3 Targeting Biomaterial Preferentially Promotes Secretion of bFGF and Proliferation of iPSC-Derived Vascular Smooth Muscle Cells

Human-induced pluripotent stem cell-derived-vascular smooth muscle cells (hiPSC-VSMC) have been shown to promote angiogenesis and wound healing. However, there is a paucity of research on how the extracellular matrix (ECM) microenvironment may impact the hiPSC-VSMCs function. In this study, our objective was to understand the effect of specific ECM ligand-integrin interaction on hiPSC- VSMCs paracrine secretion, cell proliferation, and morphology. We here showed a precise modulation of hiPSC-VSMC in a fibronectin functionalized fibrillar collagen scaffold by targeting their integrin {beta}3. The secretion of proangiogenic growth factor, basic fibroblast growth factor (bFGF) was found to be fibronectin dependent via v{beta}3 integrin interactions. Also, our data indicate the possible role of a positive feedback loop between integrin {beta}3, bFGF, and matrix metalloproteinase-2 in regulating hiPSC- VSMCs morphology and cell proliferation. Finally, the secretome with improved proangiogenic activity shows potential for future regenerative applications.