In-situ oxygen-supplying ROS nanopurifier for enhanced healing of MRSA-infected diabetic wounds via microenvironment modulation

被引：2
作者：
Wang, Qi [1 ]
Luo, Zheng [1 ,2 ]
Li, Zhiguo [1 ]
Hu, Haohua [1 ]
Lin, Yuting [1 ]
Fan, Xiaotong [3 ]
Li, Zibiao [2 ,3 ,4 ]
Wu, Yun-Long [1 ]
机构：
[1] Xiamen Univ, Sch Pharmaceut Sci, State Key Lab Cellular Stress Biol, Fujian Prov Key Lab Innovat Drug Target Res, Xiamen 361102, Peoples R China
[2] Agcy Sci Tech & Res A STAR, Inst Mat Res & Engn IMRE, 2 Fusionopolis Way,Innovis 08-03, Singapore 138634, Singapore
[3] Agcy Sci Tech & Res A STAR, Inst Sustainabil Chem Energy & Environm ISCE2, 1 Pesek Rd, Singapore 627833, Singapore
[4] Natl Univ Singapore, Dept Mat Sci & Engn, Singapore 117576, Singapore
来源：
ACTA BIOMATERIALIA | 2025年 / 193卷
关键词：
In-situ oxygen supply; Hypoxia; Antiphlogosis; Antibacterial; MRSA-infected diabetic wounds; HYPERBARIC-OXYGEN; THERAPY; VANCOMYCIN;
D O I：
10.1016/j.actbio.2024.12.044
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
Hypoxia, high ROS levels and chronic inflammation are the main factors that hinder the healing of diabetic wounds. Long-term exposed wounds are prone to bacterial infection, especially MRSA infection, which exacerbates the complex wound microenvironment of diabetes and threatens patients' lives. Here, we developed a ROS nanopurifier (CSVNP), which was prepared by loading superoxide dismutase (SOD), catalase (CAT) and vancomycin into nanogels through in-situ polymerization. CSVNP can effectively increase enzyme loading and stability, and improve cascade reaction efficiency between enzymes through nanosize effect, so that CSVNP can use a variety of ROS (H2O2 and center dot O2- ) as oxygen sources to generate much oxygen in situ, which can effectively alleviate the hypoxic environment and inflammatory response of diabetic tissues, theraby promoting cell migration and angiogenesis, and accelerating wound healing. In addition, the generated oxygen can further promote the transformation of pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages and reduce pro-inflammatory factors (TNF-alpha, IL-6, and IL-1 beta) release. CSVNP can also effectively eradicate MRSA by releasing vancomycin, preventing bacterial infection from exacerbating the deterioration of diabetic wounds. This multifunctional ROS nanopurifier with antiphlogosis, antibacterial and in-situ oxygen supply, provides a new strategy with universal and translational prospects for clinical diabetic tissue damage. Statement of Significance: Methicillin-resistant staphylococcus aureus (MRSA)-infected diabetic wounds face significant challenges in clinical care, characterized by high ROS levels, acute inflammation, vascular lesions, and hypoxia, which impede healing and risk severe complications. Here, we originally developed a reactive oxygen species (ROS) nanopurifier prepared by in-situ polymerization of superoxide dismutase (SOD), catalase (CAT), and vancomycin. It uses SOD and CAT to continuously convert ROS (H2O2 and center dot O2- ) into O2 in diabetic tissues, effectively improving hypoxia and chronic inflammation, thereby promoting angiogenesis and cell proliferation and migration, and accelerating diabetic wound healing. Vancomycin can effectively kill MRSA bacteria, avoid bacterial infection spread, and reduce complications risk. This safe, efficient and easy-to-prepare ROS nanopurifier provides a general strategy for repairing MRSA-infected diabetic tissue damage.
引用
收藏
页码：334 / 347
页数：14
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