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具有近红外光热疗法、血管生成和抗炎作用的微环境响应性纳米复合水凝胶用于糖尿病感染伤口愈合

Microenvironment responsive nanocomposite hydrogel with NIR photothermal therapy, vascularization and anti-inflammation for diabetic infected wound healing.

作者信息

Zhu Shuangli, Zhao Bangjiao, Li Maocai, Wang Hao, Zhu Jiayi, Li Qingtao, Gao Huichang, Feng Qi, Cao Xiaodong

机构信息

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

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

出版信息

Bioact Mater. 2023 Mar 14;26:306-320. doi: 10.1016/j.bioactmat.2023.03.005. eCollection 2023 Aug.

Abstract

Bacterial infection, excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer. At present, most of wound repair materials are passive and can't response to the wound microenvironment, resulting in a low utilization of bioactive substances and hence a poor therapeutic effect. Therefore, it's essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality. In this work, metformin-laden CuPDA NPs composite hydrogel (Met@ CuPDA NPs/HG) was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine (Gel-DA), Cu-loaded polydopamine nanoparticles (CuPDA NPs) with hyaluronic acid modified by phenyl boronate acid (HA-PBA), which possessed good injectability, self-healing, adhesive and DPPH scavenging performance. The slow release of metformin was achieved by the interaction with CuPDA NPs, boric groups (B-N coordination) and the constraint of hydrogel network. Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently. Moreover, CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of >95% within 10 min and also the slow release of Cu to protect wound from infection for a long time. Met@ CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu. More importantly, Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway. Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria, inhibiting inflammation, improving angiogenesis and accelerating the deposition of ECM and collagen. Therefore, Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.

摘要

细菌感染、过度炎症反应和血管网络损伤是延缓糖尿病溃疡愈合的主要因素。目前,大多数伤口修复材料是被动的,无法对伤口微环境做出响应,导致生物活性物质利用率低,治疗效果不佳。因此,设计一种对伤口微环境有响应的智能伤口敷料,在多功能的基础上实现按需释药至关重要。在这项工作中,通过多巴胺修饰的明胶(Gel-DA)、负载铜的聚多巴胺纳米颗粒(CuPDA NPs)与硼酸修饰的透明质酸(HA-PBA)之间的动态苯基硼酸键合,制备了负载二甲双胍的CuPDA NPs复合水凝胶(Met@CuPDA NPs/HG),其具有良好的可注射性、自愈性、粘附性和DPPH清除性能。二甲双胍通过与CuPDA NPs、硼基团(B-N配位)相互作用以及水凝胶网络的限制实现缓慢释放。二甲双胍具有pH和葡萄糖响应释放行为,可智能地治疗不同的伤口微环境。此外,CuPDA NPs赋予水凝胶优异的光热响应性,能在10分钟内杀灭>95%的细菌,还能缓慢释放铜以长期保护伤口免受感染。Met@CuPDA NPs/HG还能使细胞向一定方向募集,并通过释放铜促进血管生成。更重要的是,Met@CuPDA NPs/HG通过消除ROS和抑制NF-κB途径的激活有效减轻炎症。动物实验表明,Met@CuPDA NPs/HG通过杀菌、抑制炎症、改善血管生成以及加速细胞外基质和胶原蛋白的沉积,显著促进糖尿病SD大鼠伤口愈合。因此,Met@CuPDA NPs/HG在糖尿病伤口愈合方面具有巨大的应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a126/10027510/68ad349d3743/ga1.jpg

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