A dense fibrillar collagen scaffold differentially modulates secretory function of iPSC‐derived vascular smooth muscle cells to promote wound healing

The application of human‐induced pluripotent stem cells (hiPSCs) to generate vascular smooth muscle cells (hiPSC‐VSMCs) in abundance is a promising strategy for vascular regeneration. While hiPSC‐VSMCs have already been utilized for tissue‐engineered vascular grafts and disease modeling, there is a lack of investigations exploring their therapeutic secretory factors. The objective of this manuscript was to understand how the biophysical property of a collagen‐based scaffold dictates changes in the secretory function of hiPSC‐VSMCs while developing hiPSC‐VSMC‐based therapy for durable regenerative wound healing. We investigated the effect of collagen fibrillar density (CFD) on hiPSC‐VSMC’s paracrine secretion and cytokines via the construction of varying density of collagen scaffolds. Our study demonstrated that CFD is a key scaffold property that modulates the secretory function of hiPSC‐VSMCs. This study lays the foundation for developing collagen‐based scaffold materials for the delivery of hiPSC‐VSMCs to promote regenerative healing through guiding paracrine signaling pathways.