Crystal Form‐Dependent MnS for Diabetic Wound Healing: Performance and Mechanistic Insights

Abstract In pharmaceuticals, the structural and functional alterations induced by biotransformation are well‐documented. Many pharmaceuticals exist in various crystal forms, which govern their transformation and significantly impact their activity. However, in the field of inorganic nanomedicine, there is a paucity of research focusing on the influence of crystal form‐dependent “metabolism” (transformation) on their activity and biomechanism. This study delves into the distinct performances of two crystal forms of manganese sulfide (MnS), namely α‐MnS and γ‐MnS, in bacteria‐infected diabetic wound healing. In the initial stage of a wound, where the environment is neutral to slightly alkaline, MnS partially converts to Mn x O y (comprising Mn 2 O 3 and Mn 3 O 4 ) and concurrently produces hydrogen sulfide (H 2 S); the conversion efficiency of γ‐MnS significantly surpasses that of α‐MnS. Additionally, γ‐MnS is more soluble than α‐MnS, which allows it to generate more Mn 2+ . These components collectively contribute to the superior bacteriostatic properties of MnS. In wound related cells, MnS stimulates the production of collagen I and vascular endothelial growth factor (VEGF), promote the M1 macrophages polarizing to the M2 phenotype, for extracellular matrix (ECM) remodeling. Notably, different transformation products have distinct functions. Consequently, the activity of MnS is dependent on its original crystal form related solubility and transformation efficiency.