Nanodefensin-encased hydrogel with dual bactericidal and pro-regenerative functions for advanced wound therapy

作者：Gan Luo, Yaqi Sun, Jue Zhang, Zhipeng Xu, Wuyuan Lu, Hanbin Wang, Yan Zhang, Hui Li, Zhengwei Mao, Shixin Ye, Baoli Cheng, Xiangming Fang · 发表于：Theranostics · 年份：2021 · DOI：10.7150/thno.53089 · 被引用次数：30 · 研究领域：Antimicrobial Peptides and Activities、Wound Healing and Treatments、Silk-based biomaterials and applications

Background: Host defense peptides (HDPs) have emerged as a novel therapeutic paradigm for wound management; however, their clinical applications remain a challenge owing to their poor pharmacological properties and lack of suitable pharmaceutical formulations. Nanodefensin (ND), a nanoengineered human -defensin 5 (HD5), has shown improved pharmacological properties relative to the parent compound. In this study, we engineered a nanodefensin-encased hydrogel (NDEFgel), investigated the effects of NDEFgel on wound healing, and elucidated underlying mechanisms. Method: ND was chemically synthesized and tested functions by in vitro antimicrobial and scratch assays and western blotting. Different NDEFgels were evaluated by in vitro characterizations including degradation, drug release and antimicrobial activity. In full-thickness excisional murine models, the optimal NDEFgel was directly applied onto wound sites, and the efficacy was assessed. Moreover, the underlying mechanisms of pro-regenerative effect developed by NDEFgel were also explored. Results: Apart from bactericidal effects, ND modulated fibroblast behaviors by promoting migration and differentiation. Among the tested hydrogels, the Pluronic F127 (Plu) hydrogel represented the most desirable carrier for ND delivery owing to its favorable controlled release and compatibility with ND. Local treatment of NDEFgel on the wound bed resulted in accelerated wound regeneration and attenuated bacterial burden. We further demonst...