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 universal law and the underlying 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 enhancing the paracrine function of BMSCs. Topology scaffolds prove that the paracrine function of BMSCs positively correlates to the limited spreading state of cells, while independent of cell shape and specific topology structures. The enhancement in the paracrine function of BMSCs originates from mechanotransduction-related metabolism reprogramming, which is dominated by activated focal adhesions (FAs) and stress fibers 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.

Note:
Funding declaration: The study was financially supported by grants from National Key R&D Program of China (Grant No. 2021YFA1101100), Natural Science Foundation of Chongqing (Grant No. CSTB2024NSCQ-MSX0895), National Nature Science Foundation of China (Grant Nos. 82372528 and 82202459), Chongqing Health Commission Young Top Talents, China (Grant No. YXQN202432), Southwest Hospital Boqing Tuoju, China (Grant No. 2024BQTJ-4), and Chongqing Postdoctoral Research Project (Grant No. 2022CQBSHTB3043).

Conflict of Interests: The author has no conflict of interest.

Ethical Approval: All procedures involving animals were approved by the Laboratory Animal Welfare and Ethics Committee of Third Military Medical University (TMMU, AMUWEC20242065). Healthy male SD rats weighing 180-220 g were offered by Animal Center of TMMU, and were used for in vivo wound healing experiments

Keywords: Topology scaffold, BMSCs, Paracrine, Mechanotransduction, Metabolism reprogramming, Burn wounds