Butyrate-loaded gelatin methacryloyl microneedle accelerates diabetic wound healing through enhanced lipid metabolism and M2 macrophage polarization.

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.