糖基化
伤口愈合
弹性蛋白
愤怒(情绪)
融合蛋白
血管生成
促炎细胞因子
体内
受体
体外
医学
化学
炎症
药理学
免疫学
癌症研究
病理
内科学
生物
生物化学
重组DNA
神经科学
生物技术
基因
作者
Hwan June Kang,Suneel Kumar,Biraja C. Dash,Henry C. Hsia,Martin L. Yarmush,François Berthiaume
出处
期刊:Advances in wound care
[Mary Ann Liebert]
日期:2023-05-01
卷期号:12 (5): 241-255
被引量:3
标识
DOI:10.1089/wound.2021.0102
摘要
Objective: Chronic skin wounds are one of the most devastating complications in diabetic patients due to the formation of advanced glycation end-products (AGEs) resulting from nonenzymatic glycation of proteins and lipids in hyperglycemia. AGEs, upon binding their receptors (RAGEs), trigger proinflammatory signals that impair wound healing in diabetes and contribute to the pathology of chronic skin wounds. Approach: We previously developed a recombinant fusion protein containing the binding domain of RAGE (vRAGE) linked to elastin-like polypeptides (ELPs) that acts as a competitive inhibitor of AGEs, and another ELP fusion protein containing stromal cell-derived factor 1 (SDF1) that promotes revascularization. In this study, we report the effects of protein coacervates incorporating both vRAGE-ELP and SDF1-ELP on wound healing in an in vitro diabetes-mimicking cell culture system, and in in vivo in full-thickness wounds on diabetic mice. Results: The combination of vRAGE-ELP and SDF1-ELP increased cell metabolic activity in AGE-stimulated endothelial cells, promoted in vitro tube formation and accelerated healing in an in vitro cell migration assay. When used in a single topical application on full-thickness excisional skin wounds in diabetic mice, wound closure in the combination groups reached almost 100% on postwounding day 35, compared to 62% and 85% on the same days in animals treated with fibrin gel control and vehicle control consisting of ELP alone. Innovation: To our knowledge, this is the first study that attempts to reverse the AGE-RAGE-mediated signaling as well as to promote cell proliferation and vascularization in one single treatment. Conclusion: The codelivery of vRAGE-ELP and SDF1-ELP has potential for the treatment of diabetic wounds.
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