Mitochondria-protective polysaccharide augments burn wound repair through immunometabolic reprogramming

Effective wound healing requires coordinated extracellular matrix (ECM) deposition, immune regulation, and metabolic adaptation-processes governed by fibroblast mitochondria. Conventional burn therapies fail to address the mitochondrial dysfunction that impedes tissue regeneration. Here, we show that colanic acid (CA), a microbial-derived exopolysaccharide, acts as a mitochondrial-protecting biomaterial that accelerates burn repair by restoring immuno-metabolic crosstalk. In a murine deep second-degree burn model, CA enhanced wound closure 3.1-fold over controls, reduced reactive oxidative species by 54%, and increased mature collagen deposition by 193%. Mechanistically, CA undergoes intracellular internalization with the assistance of the membrane receptor TLR4 and maintains mitochondrial integrity, evidenced by restored cristae ultrastructure, a 1.4-fold increase in oxidative phosphorylation flux, and a 1.5-fold elevation in ATP production-effects abolished upon silencing the mitochondrial regulator Thap11. Bulk RNA-seq indicated that CA reshaped the wound immune landscape by driving macrophage recruitment and M2 polarization via mitochondrial metabolic reprogramming. By synchronizing mitochondrial rescue with immune-guided ECM remodeling, CA outperformed hyaluronic acid dressings in wound closure and extracellular matrix remodeling.The preliminary translational proof-of-concept of CA was confirmed in a Bama minipig model of deep second-degree burn wound, where it enhanced re-epithelialization, angiogenesis, and tissue perfusion. Together, these findings suggest that CA is a multifunctional polysaccharide with mitochondrial protective effects capable of addressing the multifaceted pathology of burn wounds across species.