Topology scaffolds-enhanced paracrine of BMSCs through mechanotransduction-related metabolism reprogramming for burn wounds healing.

Abstract

Paracrine function of mesenchymal stem cells (MSCs) plays the core role in applying for tissue regeneration and repair, which can be enhanced by various strategies. However, the underlying law and mechanism of enhancing paracrine function through topology structures remain deficiency. Herein, a series of topology scaffolds are developed to culture bone marrow mesenchymal stem cells (BMSCs) without additional biochemical stimulators, which can significantly promote paracrine-related cytokines expression through mediating cytoskeleton-related mechanotransduction. Topology scaffolds prove that the paracrine function of BMSCs positively correlates to the limited spreading state of cells, while independent of cell shape or specific topology structures. The enhancement in the paracrine function of BMSCs originates from mechanotransduction-related metabolism reprogramming, dominated by depressing cytoskeleton spreading on topology scaffolds. Up-regulated paracrine-related cytokines can effectively enhance vascularization, inhibit apoptosis, depress inflammatory responses, and promote anti-inflammatory cytokines expression. Topology scaffolds-enhanced paracrine of BMSCs can significantly promote healing rate and quality of deep II-degree burn wounds, based on inhibiting inflammatory levels and enhancing collagen deposition and angiogenesis. The novel strategy may overcome side effects of MSCs therapy and can extend topology scaffolds to more complicated tissue repairing situation.