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基于生物活性玻璃的纳米酶复合大孔冷冻凝胶,具有抗氧化、抗菌和促进愈合特性,用于糖尿病感染伤口修复。

Bioactive Glasses-Based Nanozymes Composite Macroporous Cryogel with Antioxidative, Antibacterial, and Pro-Healing Properties for Diabetic Infected Wound Repair.

作者信息

Zhu Shuangli, Li Maocai, Wang Zetao, Feng Qi, Gao Huichang, Li Qingtao, Chen Xiaofeng, Cao Xiaodong

机构信息

School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510641, P. R. China.

National Engineering Research Centre for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, P. R. China.

出版信息

Adv Healthc Mater. 2023 Nov;12(29):e2302073. doi: 10.1002/adhm.202302073. Epub 2023 Aug 24.

Abstract

The treatment for diabetic ulcers still remains a big clinic challenge owing to the adverse repair microenvironment. Bioactive glasses (BGs) play an important role in the late stages of healing due to their ability to promote vascularization and collagen fiber deposition, but fail to improve infection and oxidative stress in the early stage.Therefore, it is critical to develop a material involved in regulating the whole healing phases. In this work, BGs-based nanozymes (MnO @PDA-BGs) with antioxidation, antibacterial and pro-healing abilities are synthesized by the redox deposition of MnO on mesoporous BGs. Afterward, cryogel with the interconnected macropore structure is fabricated by the polymerization of methacrylate anhydride gelatin (GelMA) at -20 °C. MnO @PDA-BGs are loaded into the cryogel to obtain nanocomposite cryogel (MnO @PDA-BGs/Gel) with multiple enzymes-like- activities to eliminate reactive oxygen species (ROS). Besides, MnO @PDA-BGs/Gel has intensive peroxidase-like activity under acidic condition and near infrared photothermal responsiveness to achieve excellent antibacterial performance. Cells experiments demonstrate that MnO @PDA-BGs/Gel recruits L929s and promotes their proliferation. Furthermore, MnO @PDA-BGs/Gel eliminates intracellular overexpressed ROS and maintains the viability of L929s. Animal experiments confirm that MnO @PDA-BGs/Gel promotes wound healing and avoided scarring by killing bacteria, reversing inflammation, promoting vascularization, and improving the deposition of collagen III.

摘要

由于不利的修复微环境,糖尿病溃疡的治疗仍然是一个重大的临床挑战。生物活性玻璃(BGs)因其促进血管生成和胶原纤维沉积的能力,在愈合后期发挥着重要作用,但在早期阶段无法改善感染和氧化应激。因此,开发一种能够调节整个愈合阶段的材料至关重要。在这项工作中,通过MnO在介孔BGs上的氧化还原沉积合成了具有抗氧化、抗菌和促愈合能力的BGs基纳米酶(MnO@PDA-BGs)。随后,通过甲基丙烯酸酐明胶(GelMA)在-20°C下聚合制备具有相互连接大孔结构的冷冻凝胶。将MnO@PDA-BGs负载到冷冻凝胶中,获得具有多种类酶活性以消除活性氧(ROS)的纳米复合冷冻凝胶(MnO@PDA-BGs/Gel)。此外,MnO@PDA-BGs/Gel在酸性条件下具有强烈的过氧化物酶样活性和近红外光热响应性,以实现优异的抗菌性能。细胞实验表明,MnO@PDA-BGs/Gel招募L929s并促进其增殖。此外,MnO@PDA-BGs/Gel消除细胞内过表达的ROS并维持L929s的活力。动物实验证实,MnO@PDA-BGs/Gel通过杀菌、逆转炎症、促进血管生成和改善III型胶原沉积来促进伤口愈合并避免瘢痕形成。

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