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形成的基于弹性蛋白的水凝胶通过促进先天免疫细胞募集和血管生成来增强伤口愈合。

formed elastin-based hydrogels enhance wound healing via promoting innate immune cells recruitment and angiogenesis.

作者信息

Tian Duo-Mei, Wan Huan-Huan, Chen Jia-Reng, Ye Yong-Bin, He Yong, Liu Yu, Tang Lu-Yao, He Zhong-Yuan, Liu Kai-Zheng, Gao Chong-Jian, Li Sheng-Lin, Xu Qian, Yang Zheng, Lai Chen, Xu Xiao-Jun, Ruan Chang-Shun, Xu Yun-Sheng, Zhang Chao, Luo Liang, Yan Le-Ping

机构信息

Department of Critical Care Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, PR China.

Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, PR China.

出版信息

Mater Today Bio. 2022 May 21;15:100300. doi: 10.1016/j.mtbio.2022.100300. eCollection 2022 Jun.

Abstract

Harnessing the inflammation and angiogenesis is extremely important in wound healing. In this study, we developed bioactive elastin-based hydrogels which can recruit and modulate the innate immune cells and accelerate angiogenesis in the wound site and subsequently improve wound regeneration. These hydrogels were formed by visible-light cross-linking of acryloyl-(polyethylene glycol)-N-hydroxysuccinimide ester modified elastin with methacrylated gelatin, in order to mimic dermal microenvironment. These hydrogels showed highly tunable mechanical properties, swelling ratios and enzymatic degradation profiles, with moduli within the range of human skin. To mimic the degradation of the elastin by elastase from neutrophils, co-culture of the hydrogels and neutrophils was conducted. The derived conditioned medium containing elastin derived peptides (EDP-conditioned medium) promoted the expression of both M1 and M2 markers in M1 macrophages . Additionally, the EDP-conditioned medium induced superior tube formation of endothelia cells in Matrigel. In mice wound model, these elastin-based hydrogels attracted abundant neutrophils and predominant M2 macrophages to the wound and supported their infiltration into the hydrogels. The outstanding immunomodulatory effect of the elastin-based hydrogels resulted in superior angiogenesis, collagen deposition and dermal regeneration. Hence, these elastin-based hydrogels can be a promising regenerative platform to accelerate wound repair.

摘要

利用炎症和血管生成在伤口愈合中极为重要。在本研究中,我们开发了基于生物活性弹性蛋白的水凝胶,其可以募集和调节先天免疫细胞,并加速伤口部位的血管生成,进而促进伤口再生。这些水凝胶通过丙烯酰基-(聚乙二醇)-N-羟基琥珀酰亚胺酯修饰的弹性蛋白与甲基丙烯酸化明胶的可见光交联形成,以模拟真皮微环境。这些水凝胶表现出高度可调的机械性能、溶胀率和酶降解特性,其模量在人体皮肤范围内。为了模拟中性粒细胞弹性蛋白酶对弹性蛋白的降解,进行了水凝胶与中性粒细胞的共培养。含有弹性蛋白衍生肽的条件培养基(EDP条件培养基)促进了M1巨噬细胞中M1和M2标志物的表达。此外,EDP条件培养基诱导基质胶中内皮细胞形成更好的管状物。在小鼠伤口模型中,这些基于弹性蛋白的水凝胶吸引了大量中性粒细胞和主要的M2巨噬细胞至伤口处,并支持它们浸润入水凝胶中。基于弹性蛋白的水凝胶出色的免疫调节作用导致了更好的血管生成、胶原蛋白沉积和真皮再生。因此,这些基于弹性蛋白的水凝胶可能是加速伤口修复的一个有前景的再生平台。

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