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用于止血和感染伤口管理的仿生多功能可注射水凝胶

Bioinspired multifunctional injectable hydrogel for hemostasis and infected wound management.

作者信息

Fang Wen, Yang Ling, Chen Yihao, Hu Qiaoling

机构信息

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.

Jiaxing Key Laboratory of Flexible Electronics based Intelligent Sensing and Advanced Manufacturing Technology, Institute of Flexible Electronics Technology of THU, Jiaxing, China.

出版信息

Acta Biomater. 2023 Apr 15;161:50-66. doi: 10.1016/j.actbio.2023.01.021. Epub 2023 Jan 12.

Abstract

Routine wound management faces significant challenges including rebleeding and bacterial infection that affect millions of people each year. However, conventional wound dressings (e.g., gauze, bandage) are limited to simply cover the injured surfaces and rarely show special functionality to promote the wound recovery. Currently, injectable hydrogels have been widely designed as multifunctional wound dressings to manage the hemostatic and wound healing process. Nevertheless, the integration of multiple functions through simple composition and easy construction is still difficult and hardly achieved. Herein, we reported a bioinspired multifunctional injectable hydrogel (CQCS@gel) consisted of only two components, catechol-functionalized quaternized chitosan (CQCS) and dibenzaldehyde-terminated poly(ethylene glycol) (DB-PEG). The building blocks endowed CQCS@gel with tissue-adhesive, antibacterial, antioxidant, self-healing and pH-responsive properties. Based on the in vivo hemostatic study, quick hemostasis for acute tissue injuries such as liver and carotid wounds was realized owing to the rapid gelation rate and strong tissue-adhesiveness of CQCS@gel. Moreover, CQCS@gel remarkably boosted the chronic recovery process of MRSA-infected cutaneous wounds by promoting collagen deposition, hair follicles regeneration and angiogenesis. Overall, this multifunctional injectable hydrogel shows potentials as a universal wound dressing in clinical applications, enabling both hemostasis and infected wound management. STATEMENT OF SIGNIFICANCE: This is the first report showing the multifunctional injectable hydrogel (CQCS@gel) consisted of catechol-functionalized quaternized chitosan and dibenzaldehyde-terminated poly(ethylene glycol). The incorporation of quaternary ammonium groups imparted the CQCS@gel with outstanding contact-active bacterial killing efficiency and the catechol moieties enhanced its tissue adhesive and antioxidant properties. Moreover, the reversible imine crosslinks endowed the CQCS@gel with self-healing and pH-responsive drug release capabilities. These multiple functions were integrated into a single injectable hydrogel system with easy availability and low cost. In vitro and in vivo results showed that the newly designed hydrogel was biocompatible, realized successful sealing hemostasis under multiple bleeding scenarios and enabled accelerated healing of infected skin wounds.

摘要

常规伤口处理面临重大挑战,包括再出血和细菌感染,每年影响数百万人。然而,传统伤口敷料(如纱布、绷带)仅限于简单覆盖受伤表面,很少展现出促进伤口愈合的特殊功能。目前,可注射水凝胶已被广泛设计为多功能伤口敷料,用于管理止血和伤口愈合过程。然而,通过简单的组成和易于构建来整合多种功能仍然困难且难以实现。在此,我们报道了一种受生物启发的多功能可注射水凝胶(CQCS@凝胶),它仅由两种成分组成,即儿茶酚功能化的季铵化壳聚糖(CQCS)和二苯甲醛封端的聚乙二醇(DB-PEG)。这些构建单元赋予CQCS@凝胶组织粘附、抗菌、抗氧化、自愈和pH响应特性。基于体内止血研究,由于CQCS@凝胶的快速凝胶化速率和强大的组织粘附性,实现了对肝脏和颈动脉伤口等急性组织损伤的快速止血。此外,CQCS@凝胶通过促进胶原蛋白沉积、毛囊再生和血管生成,显著促进了耐甲氧西林金黄色葡萄球菌感染的皮肤伤口的慢性恢复过程。总体而言,这种多功能可注射水凝胶在临床应用中显示出作为通用伤口敷料的潜力,能够实现止血和感染伤口管理。重要性声明:这是首次报道由儿茶酚功能化的季铵化壳聚糖和二苯甲醛封端的聚乙二醇组成的多功能可注射水凝胶(CQCS@凝胶)。季铵基团的引入赋予CQCS@凝胶出色的接触活性细菌杀灭效率,儿茶酚部分增强了其组织粘附和抗氧化性能。此外,可逆的亚胺交联赋予CQCS@凝胶自愈和pH响应药物释放能力。这些多种功能被整合到一个单一的可注射水凝胶系统中,具有易于获得和低成本的特点。体外和体内结果表明,新设计的水凝胶具有生物相容性,在多种出血情况下实现了成功的封闭止血,并能加速感染皮肤伤口的愈合。

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