Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization. Here, we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrogel. The composite hydrogel (G-TSrP) is created by combining gelatin methacryloyl (GelMA) and nanoparticles (TSrP) composed of tannic acid (TA) and Sr. These nanoparticles are prepared using a one-step mineralization process assisted by metal-phenolic network formation. G-TSrP exhibits the ability to eliminate reactive oxygen species and direct polarization of macrophages toward M2 phenotype. It has been observed that the liberation of TA and Sr from G-TSrP actively facilitate the recruitment and up-regulation of the expression of extracellular matrix remodeling genes of macrophages, and thereby, coordinate in vivo adapted degradation of the G-TSrP. Most significantly, G-TSrP accelerates angiogenesis despite the TA's inhibitory properties, which are counteracted by the released Sr. Moreover, G-TSrP enhances wound closure under inflammation and promotes normal tissue formation with strong vessel growth. Genetic analysis confirms macrophage-mediated wound healing by the composite hydrogel. Collectively, these findings pave the way for the development of biomaterials that promote wound healing by creating regenerative environment.

中文翻译：

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细胞归巢和免疫调节复合水凝胶可有效促进伤口愈合和新生血管形成

由于新生血管形成受损，过度炎症情况下的伤口愈合面临重大挑战。在这里，我们提出了一种多功能复合水凝胶，旨在通过招募和激活巨噬细胞以及水凝胶的适应性降解来克服此类条件。复合水凝胶 (G-TSrP) 是通过将明胶甲基丙烯酰 (GelMA) 与由单宁酸 (TA) 和 Sr 组成的纳米颗粒 (TSrP) 结合而成。这些纳米颗粒是通过一步矿化工艺并辅以金属酚网络形成来制备的。G-TSrP 表现出消除活性氧和直接将巨噬细胞极化为 M2 表型的能力。据观察，从 G-TSrP 中释放 TA 和 Sr 会积极促进巨噬细胞细胞外基质重塑基因表达的募集和上调，从而协调 G-TSrP 的体内适应降解。最重要的是，尽管 TA 具有抑制特性，但 G-TSrP 仍能加速血管生成，而释放的 Sr 会抵消这种抑制特性。此外，G-TSrP 可以增强炎症下的伤口闭合，并促进正常组织形成和强血管生长。遗传分析证实了复合水凝胶可介导巨噬细胞介导的伤口愈合。总的来说，这些发现为开发通过创造再生环境促进伤口愈合的生物材料铺平了道路。