Effective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Herein, a core-shell structured microneedle array patch with programmed functions (PF-MNs) is designed to dynamically modulate the wound immune microenvironment according to the varied healing phases. Specifically, PF-MNs combat multidrug-resistant bacterial biofilm at the early stage via generating reactive oxygen species (ROS) under laser irradiation. Subsequently, the ROS-sensitive MN shell gradually degrades to expose the MN core component, which neutralizes various inflammatory factors and promotes the phase transition from inflammation to proliferation. In addition, the released verteporfin inhibits scar formation by blocking Engrailed-1 (En1) activation in fibroblasts. Our experiments demonstrate that PF-MNs promote scarless wound repair in mouse models of both acute and chronic wounds, and inhibit the formation of hypertrophic scar in rabbit ear models.

由于生理障碍阻碍了药物输送功效有限，以及不同愈合阶段的给药时机不适当，慢性伤口愈合的有效重新编程仍然具有挑战性。本文设计了一种具有编程功能的核壳结构微针阵列贴片（PF-MN），旨在根据不同的愈合阶段动态调节伤口免疫微环境。具体来说，PF-MNs 通过在激光照射下产生活性氧 (ROS) 来在早期对抗多重耐药细菌生物膜。随后，ROS敏感的MN外壳逐渐降解，暴露出MN核心成分，中和各种炎症因子，促进从炎症到增殖的相变。此外，释放的维替泊芬通过阻断成纤维细胞中Engrailed-1 ( En1 ) 的激活来抑制疤痕形成。我们的实验表明，PF-MN 可以促进小鼠急性和慢性伤口模型的无疤痕伤口修复，并抑制兔耳模型中增生性疤痕的形成。