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开发一种具有抗菌活性的聚六亚甲基双胍(PHMB)水凝胶改性伤口支架敷料。

Development of a PHMB hydrogel-modified wound scaffold dressing with antibacterial activity.

机构信息

Department of Burn & Plastic Surgery, 903rd Hospital of PLA, Hangzhou, China.

Department of Burn Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.

出版信息

Wound Repair Regen. 2020 Jul;28(4):480-492. doi: 10.1111/wrr.12813. Epub 2020 Jun 20.

DOI:10.1111/wrr.12813
PMID:32304258
Abstract

Current wound scaffold dressing constructs can facilitate wound healing but do not exhibit antibacterial activity, resulting in high infection rates. We aimed to endow wound scaffold dressing with anti-infective ability by polyhexamethylenebiguanide (PHMB). We prepared PHMB hydrogel at varying concentrations (0.25%, 0.5%, 1%, 2%) and assessed release and cytotoxicity. PHMB hydrogel was added to the wound scaffold dressing to generate a PHMB hydrogel-modified wound scaffold dressing. Wound healing and infection prevention were evaluated using a full-thickness skin defect model in rats. In vitro, the hydrogel PHMB release time positively correlated with PHMB concentration, with 1% allowing sufficiently long release time to encompass the high-incidence period (3-5 days) of infection following wound scaffold dressing implantation. Implantation of 1% PHMB hydrogel into the skin did not cause adverse responses. in vitro cytotoxicity assays showed the PHMB hydrogel-modified wound scaffold dressing did not significantly affect proliferation of fibroblasts or vascular endothelial cells, 99.90% vs 99.84% for fibroblasts and 100.21% vs 99.28% for vascular endothelial cells at 21 days. Transplantation of PHMB hydrogel-modified wound scaffold dressing/unmodified wound scaffold dressing on the non-infected wounds of rats yielded no significant difference in relative vascularization rate, 47.40 vs 50.87 per view at 21 days, whereas bacterial content of the wound tissue in the PHMB hydrogel-modified wound scaffold dressing group was significantly lower than the unmodified wound scaffold dressing group, (1.80 ± 0.35) × 10 vs (9.34 ± 0.45) × 10 at 14 days. Prevalence of persistent wound infection in the rats receiving PHMB hydrogel-modified wound scaffold dressing transplantation onto infected wounds was significantly lower than the unmodified wound scaffold dressing group, 30% vs 100%. PHMB hydrogel-modified wound scaffold dressing exhibited suitable antibacterial ability, and its biological activity did not significantly differ from that of the unmodified wound scaffold dressing, thereby allowing it to effectively prevent infection following wound scaffold dressing implantation.

摘要

目前的创面支架敷料可以促进创面愈合,但不具有抗菌活性,导致感染率高。我们旨在通过聚六亚甲基双胍(PHMB)为创面支架敷料赋予抗感染能力。我们制备了不同浓度(0.25%、0.5%、1%、2%)的 PHMB 水凝胶,并评估了释放和细胞毒性。将 PHMB 水凝胶添加到创面支架敷料中,生成 PHMB 水凝胶改性创面支架敷料。通过大鼠全层皮肤缺损模型评估创面愈合和感染预防效果。体外,水凝胶 PHMB 释放时间与 PHMB 浓度呈正相关,1%的 PHMB 浓度可提供足够长的释放时间,涵盖创面支架敷料植入后感染高发期(3-5 天)。将 1%的 PHMB 水凝胶植入皮肤不会引起不良反应。体外细胞毒性试验表明,PHMB 水凝胶改性创面支架敷料对成纤维细胞和血管内皮细胞的增殖没有显著影响,21 天时成纤维细胞为 99.90%,对血管内皮细胞为 100.21%。将 PHMB 水凝胶改性创面支架敷料/未改性创面支架敷料移植到大鼠无感染创面,21 天时相对血管化率无显著差异,分别为 47.40%和 50.87%/视野,而 PHMB 水凝胶改性创面支架敷料组的创面组织细菌含量明显低于未改性创面支架敷料组,分别为(1.80±0.35)×10和(9.34±0.45)×10 14 天。在感染创面接受 PHMB 水凝胶改性创面支架敷料移植的大鼠中,持续性创面感染的发生率明显低于未改性创面支架敷料组,分别为 30%和 100%。PHMB 水凝胶改性创面支架敷料具有适宜的抗菌能力,其生物活性与未改性创面支架敷料无显著差异,从而可以有效预防创面支架敷料植入后的感染。

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