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基于葡聚糖和肽的 pH 敏感水凝胶促进多重耐药菌感染伤口的愈合过程。

Dextran and peptide-based pH-sensitive hydrogel boosts healing process in multidrug-resistant bacteria-infected wounds.

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, PR China.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, PR China.

出版信息

Carbohydr Polym. 2022 Feb 15;278:118994. doi: 10.1016/j.carbpol.2021.118994. Epub 2021 Dec 10.

Abstract

Traumatic multidrug-resistant (MDR) bacterial infections are deadly threat to the public. To combat MDR bacteria, we developed a dual functional pH-sensitive hydrogel based on peptide DP7 (VQWRIRVAVIRK) and oxidized dextran (DP7-ODEX hydrogel). As an antimicrobial peptide, DP7 can synergize with many antibiotics; thus, we loaded ceftazidime into DP7-ODEX hydrogel, which showed an obvious advantage in MDR P. aeruginosa inhibition. Additionally, due to the interaction between aldehyde groups in oxidized dextran and amine groups from wound tissue, the hydrogel could extend on the irregular surface of skin defects and promote epithelial cells adhesion. DP7 could also be used as a wound-healing peptide and accelerate the healing process. We confirmed that the DP7-ODEX hydrogel exerted formidable therapeutic effects in normal or diabetic wound infection model. According to histomorphology analysis we found that DP7 hydrogel also have a scarless wound healing ability. In summary, we developed a hydrogel fabricated by the dual functional peptide DP7 that can kill multidrug-resistant bacteria colonizing the wound bed and boost scarless wound healing.

摘要

创伤性多重耐药(MDR)细菌感染对公众构成致命威胁。为了对抗 MDR 细菌,我们开发了一种基于肽 DP7(VQWRIRVAVIRK)和氧化葡聚糖的双重功能 pH 敏感水凝胶(DP7-ODEX 水凝胶)。作为一种抗菌肽,DP7 可以与许多抗生素协同作用;因此,我们将头孢他啶装载到 DP7-ODEX 水凝胶中,这在抑制 MDR 铜绿假单胞菌方面显示出明显的优势。此外,由于氧化葡聚糖中的醛基与伤口组织中的胺基之间的相互作用,水凝胶可以在皮肤缺陷的不规则表面上扩展,并促进上皮细胞的附着。DP7 还可以用作伤口愈合肽,加速愈合过程。我们证实 DP7-ODEX 水凝胶在正常或糖尿病伤口感染模型中发挥了强大的治疗作用。根据组织形态学分析,我们发现 DP7 水凝胶还具有无疤痕的伤口愈合能力。总之,我们开发了一种由双重功能肽 DP7 制成的水凝胶,它可以杀死定植在伤口床的多重耐药细菌并促进无疤痕的伤口愈合。

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