A multifunctional ZIF-8@CuO/collagen-binding peptide hydrogel for photothermal-enhanced antibacterial and infected skin wound management.

Owing to continuous bacterial proliferation, a persistent inflammatory response, and impaired vascularization, infected skin wounds remain a major clinical challenge. Herein, we fabricated a multifunctional skin-repair material by incorporating ZIF-8@CuO nanoparticles and a collagen-binding vascular endothelial growth factor mimetic peptide (C-VEGFMP) into a gelatin methacryloyl (GelMA) hydrogel. The ZIF-8@CuO nanoparticles were prepared by controllably depositing copper oxide (CuO) onto the surface of zeolitic imidazolate framework-8 (ZIF-8). ZIF-8@CuO can endowed the hydrogel with potent antibacterial and anti-inflammatory activities, as well as efficient near-infrared (NIR) photothermal conversion capability. C-VEGFMP was constructed by introducing a collagen-binding sequence into the VEGFMP. This modified peptide can stably anchor to GelMA and maintain its bioactivity at the hydrogel-tissue interface. The resulting ZIF-8@CuO/C-VEGFMP hydrogel exhibited favorable cytocompatibility, broad-spectrum antibacterial activity and prominent pro-angiogenic performance. Upon NIR irradiation, the photothermal effect of ZIF-8@CuO can synergistically eradicate pathogenic bacteria, thereby enhancing photothermal therapeutic efficacy. In addition, the sustained presence of bioactive C-VEGFMP promoted epithelial regeneration, collagen deposition, and neovascularization in infected full-thickness wounds. Transcriptomic analysis indicated that treatment with ZIF-8@CuO/C-VEGFMP under NIR irradiation exerted anti-inflammatory, pro-angiogenic and tissue-repair effects mainly by upregulating thrombomodulin (THBD) and Ets proto-oncogene 2 (Ets2) genes. This study provides a multifunctional strategy that combines nanoparticle-mediated photothermal antibacterial effects with functionalized peptides, offering a promising therapeutic modality for the management of infected skin injuries.