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基于生物相容性邻苯二甲醛/胺交联的可注射抗菌组织粘附水凝胶用于有效治疗感染伤口。

Injectable antibacterial tissue-adhesive hydrogel based on biocompatible o-phthalaldehyde/amine crosslinking for efficient treatment of infected wounds.

作者信息

Zou Zheng, Zhang Zhen, Ren Hui, Cheng Xueliang, Chen Xuesi, He Chaoliang

机构信息

CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China; School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.

CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.

出版信息

Biomaterials. 2023 Oct;301:122251. doi: 10.1016/j.biomaterials.2023.122251. Epub 2023 Jul 26.

DOI:10.1016/j.biomaterials.2023.122251
PMID:37531776
Abstract

Injectable antibacterial hydrogels have attracted considerable attention in wound management. However, the development of injectable hydrogels with excellent antibacterial activity, good biocompatibility, and strong tissue adhesion remains a challenge. In this study, an antibacterial tissue-adhesive hydrogel was developed based on a catalyst-free o-phthalaldehyde (OPA)/amine reaction by simply mixing OPA-terminated four-arm poly(ethylene glycol) (4aPEG-OPA) and ε-poly-l-lysine (ε-PLL) solutions. The hydrogel showed tunable gelation time, storage moduli, and degradation rate depending on the polymer concentration and 4aPEG-OPA/ε-PLL mass ratio. The hydrogel exhibited nearly 100% bacterial inhibition rates in-vitro against Gram-negative E. coli and Gram-positive S. aureus, while maintaining good biocompatibility. The hydrogel matched well in shape and tightly adhered to the tissue after in-situ formation at the wound sites. Following the treatment of rat models of full-thickness skin incisions and round wounds, the hydrogel effectively closed the wounds and promoted wound healing. Moreover, after administering to S. aureus infected full-thickness skin wounds, the hydrogel exhibited remarkable efficacy in inhibiting wound infection with a bacterial inhibition rate over 99.94%, achieving a significantly accelerated wound healing compared with the commercially available Prontosan® gel. Therefore, the hydrogel exhibits great potential as a wound dressing for infection prevention and promotion of healing.

摘要

可注射抗菌水凝胶在伤口处理方面已引起了相当大的关注。然而,开发具有优异抗菌活性、良好生物相容性和强组织粘附性的可注射水凝胶仍然是一项挑战。在本研究中,通过简单混合邻苯二甲醛(OPA)封端的四臂聚乙二醇(4aPEG-OPA)和ε-聚-L-赖氨酸(ε-PLL)溶液,基于无催化剂的OPA/胺反应开发了一种抗菌组织粘附水凝胶。该水凝胶的凝胶化时间、储能模量和降解速率可根据聚合物浓度和4aPEG-OPA/ε-PLL质量比进行调节。该水凝胶在体外对革兰氏阴性大肠杆菌和革兰氏阳性金黄色葡萄球菌表现出近100%的细菌抑制率,同时保持良好的生物相容性。该水凝胶在伤口部位原位形成后,形状匹配良好并紧密粘附于组织。在对大鼠全层皮肤切口和圆形伤口模型进行治疗后,该水凝胶有效地闭合了伤口并促进了伤口愈合。此外,在应用于金黄色葡萄球菌感染的全层皮肤伤口后,该水凝胶在抑制伤口感染方面表现出显著疗效,细菌抑制率超过99.94%,与市售的Prontosan®凝胶相比,实现了伤口愈合的显著加速。因此,该水凝胶作为一种用于预防感染和促进愈合的伤口敷料具有巨大潜力。

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