血管生成
伤口愈合
新生血管
促炎细胞因子
糖尿病
离体
体内
下调和上调
药理学
免疫系统
医学
免疫学
炎症
癌症研究
生物
内分泌学
生物化学
生物技术
基因
作者
Peng Xiang,Meng Jiang,Xin Chen,Lingyun Chen,Yalun Cheng,Xiang‐Hang Luo,Haiyan Zhou,Yongjun Zheng
标识
DOI:10.1002/advs.202305856
摘要
Abstract Chronic diabetic wounds are a serious complication of diabetes and often result in limb amputations and confer high mortality rates. The proinflammatory secretome in the wound perpetuates defective neovascularization and contributes to dysregulated tissue repair. This study aims to design a gelatin methacrylamide (GelMA) hydrogel to sustained the release of grancalcin‐neutralizing antibody (GCA‐NAb) and evaluate it as a potential scaffold to promote diabetic wound healing. Results show that the expression of grancalcin(GCA), a protein secreted by bone marrow‐derived immune cells, is elevated in the wound sites of individuals and animals with diabetic ulcers. Genetic inhibition of grancalcin expression accelerates vascularization and healing in an animal model. Mechanistic studies show that grancalcin binds to transient receptor potential melastatin 8(TRPM8) and partially inactivates its downstream signaling pathways, thereby impairing angiogenesis in vitro and ex vivo. Systemic or topical administration of a GCA‐NAb accelerate wound repair in mice with diabetes. The data suggest that GCA is a potential therapeutic target for the treatment of diabetic ulcers.
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