Acceleration of Esophageal Wound Healing by Anisotropically Aligned Smooth Muscle Cell-Laden Nanofibrous Patch

Abstract Background Esophageal tissue engineering is proposed to repair damaged esophagus, which requires peristalsis via directional alignment and movement of smooth muscle. Cell electrospinning (CE) is an effective technique to produce aligned muscle tissues by directly encapsulating living cells into micro/nanofibers. Mesenchymal stem cells (MSCs) can differentiate into smooth muscle cells (SMCs) in response to treatment with transforming growth factor-β1. In this study, we investigated the phenotypic changes of MSCs and MSC-derived SMCs via CE, and evaluated the therapeutic effect of SMC-patch for esophageal wound model. Methods MSCs and SMCs were fabricated with 2 wt % alginate and 3 wt % PEO, and the cell-laden bioink was printed and electrospun onto PCL scaffolds for random and anisotropic alignment, respectively. In in vivo test, the SMC-patch was construct by CE and the rat’s esophageal wound model was developed by tissue punching. The SMC-patch was transplanted with sutures in the esophageal defect. Results Cell electrospinning resulted in more aligned and elongated forms of MSCs and SMCs than bioprinting. SMCs aligned via cell electrospinning exhibited upregulated expression of SMC-specific markers (alpha-smooth muscle actin, calponin, SM22α, and desmin), SMC-associated extracellular matrix proteins (fibronectin, collagen types I and IV), and connexin 43, the principal gap junction protein in SMCs. The electrospun SMC was fabricated in a patch form and transplanted into a rat esophageal wound model. Transplantation of the smooth muscle patch promoted muscle regeneration and vascularization in esophageal wounds. Conclusion Taken together, these results suggest that transforming growth factor-β1-induced differentiation of MSCs to SMCs and anisotropic alignment of SMCs can be applied to engineer smooth muscle tissues and treat gastrointestinal perforation.