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用于感染烧伤创面愈合的细菌生长诱导妥布霉素智能释放自愈合水凝胶

Bacterial Growth-Induced Tobramycin Smart Release Self-Healing Hydrogel for -Infected Burn Wound Healing.

作者信息

Huang Ying, Mu Lei, Zhao Xin, Han Yong, Guo Baolin

机构信息

State Key Laboratory for Mechanical Behavior of Materials and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710049, China.

出版信息

ACS Nano. 2022 Aug 23;16(8):13022-13036. doi: 10.1021/acsnano.2c05557. Epub 2022 Aug 3.

Abstract

Burns are a common health problem worldwide and are highly susceptible to bacterial infections that are difficult to handle with ordinary wound dressings. Therefore, burn wound repair is extremely challenging in clinical practice. Herein, a series of self-healing hydrogels (QCS/OD/TOB/PPY@PDA) with good electrical conductivity and antioxidant activity were prepared on the basis of quaternized chitosan (QCS), oxidized dextran (OD), tobramycin (TOB), and polydopamine-coated polypyrrole nanowires (PPY@PDA NWs). These Schiff base cross-links between the aminoglycoside antibiotic TOB and OD enable TOB to be slowly released and responsive to pH. Interestingly, the acidic substances during the bacteria growth process can induce the on-demand release of TOB, avoiding the abuse of antibiotics. The antibacterial results showed that the QCS/OD/TOB/PPY@PDA9 hydrogel could kill high concentrations of (PA), , and in a short time and showed a bactericidal effect for up to 11 days in an agar plate diffusion experiment, while showing good antibacterial activity. Excellent and long-lasting antibacterial properties make it suitable for severely infected wounds. Furthermore, the incorporation of PPY@PDA endowed the hydrogel with near-infrared (NIR) irradiation assisted bactericidal activity of drug-resistant bacteria, conductivity, and antioxidant activity. Most importantly, in the PA-infected burn wound model, the QCS/OD/TOB/PPY@PDA9 hydrogel more effectively controlled wound inflammation levels and promoted collagen deposition, vascular generation, and earlier wound closure compared to Tegaderm dressings. Therefore, the TOB smart release hydrogels with on-demand delivery are extremely advantageous for bacterial-infected burn wound healing.

摘要

烧伤是全球常见的健康问题,极易受到细菌感染,普通伤口敷料难以应对。因此,烧伤创面修复在临床实践中极具挑战性。在此,基于季铵化壳聚糖(QCS)、氧化葡聚糖(OD)、妥布霉素(TOB)和聚多巴胺包覆的聚吡咯纳米线(PPY@PDA NWs)制备了一系列具有良好导电性和抗氧化活性的自愈合水凝胶(QCS/OD/TOB/PPY@PDA)。氨基糖苷类抗生素TOB与OD之间的这些席夫碱交联使TOB能够缓慢释放并对pH作出响应。有趣的是,细菌生长过程中的酸性物质可诱导TOB按需释放,避免抗生素滥用。抗菌结果表明,QCS/OD/TOB/PPY@PDA9水凝胶能在短时间内杀灭高浓度的铜绿假单胞菌(PA)、金黄色葡萄球菌和大肠杆菌,在琼脂平板扩散实验中显示出长达11天的杀菌效果,同时表现出良好的抗MRSA抗菌活性。优异且持久的抗菌性能使其适用于严重感染的伤口。此外,PPY@PDA的加入赋予水凝胶对耐药菌的近红外(NIR)照射辅助杀菌活性、导电性和抗氧化活性。最重要的是,在PA感染的烧伤创面模型中,与德湿可敷料相比,QCS/OD/TOB/PPY@PDA9水凝胶能更有效地控制伤口炎症水平,促进胶原蛋白沉积、血管生成并加速伤口愈合。因此,具有按需递送功能的TOB智能释放水凝胶对细菌感染的烧伤创面愈合极为有利。

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