抗菌剂
明胶
化学
抗菌肽
自愈水凝胶
PEG比率
半胱氨酸
肽
谷胱甘肽
药理学
生物化学
药物输送
透明质酸
伤口愈合
药品
抗菌药物
组合化学
氨基酸
免疫系统
毒品携带者
组织工程
再生(生物学)
生物活性
烧伤
慢性伤口
抗生素
作者
Xin Liu,Zekai Ren,Yumei Wang,Han Wu,Hailin Cong,Bing Yu
出处
期刊:Biomacromolecules
[American Chemical Society]
日期:2025-09-19
卷期号:26 (10): 6613-6624
标识
DOI:10.1021/acs.biomac.5c00859
摘要
Chronic wounds represent a major global health challenge, characterized by impaired healing, localized necrosis, and, in advanced stages, potential limb loss. The delayed healing process is multifactorial, involving the accumulation of exudate, microbial colonization, and immune dysfunction. Building upon our previous work with the broad-spectrum antimicrobial peptide LKAHR, this study introduces structural modifications via site-specific cysteine conjugation and alkyl chain functionalization. The mechanical properties of gelatin hydrogels were optimized through PEG cross-linking to improve drug delivery capabilities. Three modified antimicrobial peptides (AMPs) were systematically assessed for hemocompatibility, antimicrobial efficacy, and radical scavenging activity, with Cys2-LKAHR-C8 emerging as the top candidate. This optimized peptide demonstrated a 50% enhancement in antimicrobial efficacy compared to native LKAHR, along with potent free radical neutralization capacity. Mechanistically, it exerts hepatoprotective effects through glutathione-mimetic redox regulation. In translational validation, the PEG-gelatin hydrogel-mediated delivery of Cys2-LKAHR-C8 achieved 78% wound closure efficiency in chronic wounds, demonstrating sustained antimicrobial activity and improved tissue regeneration in burn infection models.
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