Mesoporous bioactive glass-recombinant collagen III nanocomposite capsule promotes skin wound healing via adaptive immune modulation.

Chronic skin wounds remain a clinical challenge due to impaired extracellular matrix (ECM) reconstruction and dysregulated immune responses. Biomaterials that simultaneously support matrix formation and modulate the wound immune microenvironment are, therefore, highly desirable. Here, we developed a mesoporous bioactive glass-recombinant collagen III nanocomposite capsule (Cap-ReCol III), in which recombinant collagen III is adsorbed onto mesoporous bioactive glass nanoparticles to form an integrated organic-inorganic unit. Cap-ReCol III exhibited a well-defined mesoporous structure and favorable physicochemical properties. In vitro, it showed excellent cytocompatibility and significantly enhanced fibroblast proliferation, migration and contractility, accompanied by increased expression of α-smooth muscle actin and collagen-related markers. In a full-thickness mouse wound model, Cap-ReCol III accelerated wound closure and promoted granulation tissue formation and collagen deposition. Importantly, Cap-ReCol III modulated the immune microenvironment by reducing neutrophil accumulation and granzyme B+ CD8+ T cells, while increasing regulatory T cells and IL-13+ CD8+ T-cell subsets associated with tissue repair. Adoptive transfer experiments in Rag2-/- mice further confirmed the essential role of adaptive immunity in this process. Overall, Cap-ReCol III promotes wound healing by coordinating ECM remodeling and adaptive immune modulation, providing a promising strategy for skin regeneration.