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可注射自修复益生菌负载水凝胶促进超级细菌感染伤口愈合

Injectable and Self-Healing Probiotics-Loaded Hydrogel for Promoting Superbacteria-Infected Wound Healing.

机构信息

Institute for Translational Medicine, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.

Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin 300038, China.

出版信息

ACS Appl Mater Interfaces. 2022 May 11;14(18):20538-20550. doi: 10.1021/acsami.1c23713. Epub 2022 Apr 26.

DOI:10.1021/acsami.1c23713
PMID:35471815
Abstract

Superbacteria-induced skin wound infections are huge health challenges, resulting in significant financial and medical costs due to notable morbidity and mortality worldwide. Probiotics are found in the skin and are effective in treating bacterial infection, moderating the microbial dysbiosis and inflammation induced by pathogens, regulating the immune system, as well as even promoting tissue repair. However, improving their colonization efficiency and viability remains a large obstacle for proper applications. Inspired by probiotic therapy and the natural extracellular matrix structure, hyaluronate-adipic dihydrazide/aldehyde-terminated Pluronic F127/fucoidan hydrogels loaded with (HPF@L.rha) with unique (bio)physicochemical characteristics were developed through the dynamic Schiff-base reaction for superbacteria-infected trauma management. The developed HPF@L.rha exhibit a shortened gelation time, enhanced mechanical strength, and excellent self-healing and liquid-absorption abilities. Importantly, their anti-superbacteria () effect was greatly increased in a dose-dependent fashion. Additionally, evaluation shows that the prepared HPF@L.rha containing appropriate probiotic concentrations (less than 1 × 10 CFU/mL) possess satisfactory cytocompatibility and blood compatibility. Further, compared to the HPF hydrogel, the hydrogel combined with probiotics significantly inhibits infection and inflammation, promotes the formation of re-epithelialization and collagen, and thus accelerates full-thickness superbacteria-infected wound repair, which is comparable to commercial Prontosan gel formulation. This work suggests that the combination of biomimicking hydrogels and probiotic therapy displays the great potential to manage superbug-infected trauma.

摘要

超级细菌诱导的皮肤伤口感染是巨大的健康挑战,由于全球发病率和死亡率高,导致了巨大的经济和医疗成本。益生菌存在于皮肤中,可有效治疗细菌感染,调节病原体引起的微生物失调和炎症,调节免疫系统,甚至促进组织修复。然而,提高其定植效率和活力仍然是适当应用的一个巨大障碍。受益生菌治疗和天然细胞外基质结构的启发,通过动态席夫碱反应,开发了具有独特(生物)物理化学特性的透明质酸-己二酰肼/醛封端的泊洛沙姆 F127/褐藻糖胶水凝胶负载(HPF@L.rha),用于治疗超级细菌感染的创伤。所开发的 HPF@L.rha 具有较短的凝胶时间、增强的机械强度以及出色的自修复和液体吸收能力。重要的是,它们的抗超级细菌()效果呈剂量依赖性显著增加。此外,评估表明,含有适当益生菌浓度(低于 1×10 CFU/mL)的制备好的 HPF@L.rha 具有令人满意的细胞相容性和血液相容性。此外,与 HPF 水凝胶相比,含有益生菌的水凝胶可显著抑制 感染和炎症,促进再上皮化和胶原形成,从而加速全厚度超级细菌感染伤口的修复,与商业 Prontosan 凝胶制剂相当。这项工作表明,仿生水凝胶与益生菌治疗的结合具有管理超级细菌感染创伤的巨大潜力。

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