There is an increasingly growing demand to balance tissue repair guidance and opportunistic infection (OI) inhibition in clinical implant surgery. Herein, we developed a nanoadjuvant for all-stage tissue repair guidance and biofilm-responsive OI eradication via in situ incorporating Cobaltiprotoporphyrin (CoPP) into Prussian blue (PB) to prepare PB-CoPP nanozymes (PCZs). Released CoPP possesses a pro-efferocytosis effect for eliminating apoptotic and progressing necrotic cells in tissue trauma, thus preventing secondary inflammation. Once OIs occur, PCZs with switchable nanocatalytic capacity can achieve bidirectional pyroptosis regulation. Once reaching the acidic biofilm microenvironment, PCZs possess peroxidase (POD)-like activity that can generate reactive oxygen species (ROS) to eradicate bacterial biofilms, especially when synergized with the photothermal effect. Furthermore, generated ROS can promote macrophage pyroptosis to secrete inflammatory cytokines and antimicrobial proteins for biofilm eradication in vivo. After eradicating the biofilm, PCZs possess catalase (CAT)-like activity in a neutral environment, which can scavenge ROS and inhibit macrophage pyroptosis, thereby improving the inflammatory microenvironment. Briefly, PCZs as nanoadjuvants feature the capability of all-stage tissue repair guidance and biofilm-responsive OI inhibition that can be routinely performed in all implant surgeries, providing a wide range of application prospects and commercial translational value.

中文翻译：

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植入手术期间通过促胞吞作用和双向细胞焦亡调节平衡生物响应性生物膜根除和引导组织修复


临床种植手术中对平衡组织修复指导和机会性感染 (OI) 抑制的需求日益增长。在此，我们通过将钴原卟啉（CoPP）原位掺入普鲁士蓝（PB）中制备PB-CoPP纳米酶（PCZ），开发了一种用于全阶段组织修复指导和生物膜响应性OI根除的纳米佐剂。释放的 CoPP 具有促细胞作用，可消除组织创伤中的凋亡和进展性坏死细胞，从而防止继发性炎症。一旦OIs发生，具有可切换纳米催化能力的PCZ可以实现双向焦亡调节。一旦到达酸性生物膜微环境，PCZ 就具有类似过氧化物酶 (POD) 的活性，可以产生活性氧 (ROS) 来消灭细菌生物膜，特别是与光热效应协同作用时。此外，产生的ROS可以促进巨噬细胞焦亡，分泌炎症细胞因子和抗菌蛋白，从而消除体内生物膜。消除生物膜后，PCZs在中性环境下具有类过氧化氢酶（CAT）活性，可以清除ROS并抑制巨噬细胞焦亡，从而改善炎症微环境。简而言之，PCZ作为纳米佐剂具有全阶段组织修复引导和生物膜响应性OI抑制的能力，可在所有种植手术中常规进行，提供广泛的应用前景和商业转化价值。