双靶向仿生纳米酶载微针贴片通过抗炎和抗纤维化作用促进无疤痕伤口愈合

Abstract

During skin wound healing, complex interactions among multiple cell types and dynamic phase evolution make it difficult for biomaterial scaffolds to balance late‐healing and over‐healing, often resulting in delayed wound healing, persistent inflammatory responses, and hypertrophic scars due to spatiotemporal mismatch. Precise regulation of fibroblast‐to‐myofibroblast transformation and macrophage polarization is therefore essential yet challenging. Fibroblast activation protein (FAP) has been identified as a key bio‐cue in pulmonary and hepatic fibrosis, but whether FAP‐targeting peptide (FTP) within a biomimetic system can address this dilemma remains unclear. Here, a methacrylated hyaluronic acid hydrogel microneedle patch (CAF@MN) integrating a dual‐targeting biomimetic nanozyme system (Cu‐CeO 2 @ABs‐FTP) modified with apoptotic bodies (ABs) membranes and FTP is developed. Cu‐CeO 2 nanocomposites activate fibroblast functions and exhibit anti‐inflammatory, antibacterial, antioxidant, and pro‐angiogenic activities. The ABs membrane enables macrophage targeting and M2 polarization, while FTP specifically modulates myofibroblast activation. The microneedle architecture enhances deep local delivery and nanozyme utilization. In mouse and rabbit full‐phase wound models, the system achieves accelerated wound healing, reduced inflammation, and attenuated hypertrophic scars. Single‐cell RNA sequencing further elucidates the dual‐targeted regulatory mechanisms underlying anti‐inflammation and scar suppression. This study developed a dual‐targeting biomimetic nanozyme hybrid system (Cu‐CeO 2 @ABs‐FTP) and integrated it with HAMA hydrogel to fabricate a microneedle patch (CAF@MN). The patch promotes fibroblast‐mediated wound repair, targets macrophages to induce M2 polarization, and targets myofibroblasts to exert anti‐fibrotic effects, thereby enabling rapid, anti‐inflammatory, and scarless wound healing.