Abstract

Diabetic wound healing is significantly impaired by persistent inflammation, metabolic dysregulation, and dysfunctional macrophage polarization. Addressing these intertwined pathologies requires innovative therapeutic strategies. Here, we developed a butyrate-loaded gelatin methacryloyl microneedle patch (Buty@MN) designed to locally reprogram metabolic-immune crosstalk within the diabetic wound microenvironment. The Buty@MN system demonstrated excellent biocompatibility, and exhibited a sustained release. In vitro, Buty@MN significantly enhanced fibroblast migration and promoted a metabolic shift in macrophages toward fatty acid oxidation (FAO), concomitant with a marked increase in anti-inflammatory M2 polarization (evidenced by upregulated IL-10, Arg-1, CD206 and downregulated IL-1β, IL-6, CD86). In vivo, treatment of full-thickness diabetic wounds in mice with Buty@MN accelerated wound closure (95.5 ± 1.8% vs. 72.0 ± 7.4% in controls at day 14, P  < 0.01), enhanced re-epithelialization, promoted collagen deposition, and stimulated angiogenesis. These findings establish Buty@MN as a potent therapeutic platform, which offers a promising approach for enhancing diabetic wound repair.