模拟慢性伤口愈合级联反应以促进皮肤修复的响应性多功能水凝胶。

Responsive multifunctional hydrogels emulating the chronic wounds healing cascade for skin repair.

作者信息

Zhang Wen, Liu Wenqi, Long Linyu, He Shuyi, Wang Zhicun, Liu Yang, Yang Li, Chen Ningbo, Hu Cheng, Wang Yunbing

机构信息

National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, People's Republic of China.

Department of Plastic and Burn Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

J Control Release. 2023 Feb;354:821-834. doi: 10.1016/j.jconrel.2023.01.049. Epub 2023 Jan 30.

Abstract

It remains challenging to cure chronic diabetic wounds due to its' harsh microenvironment and poor tissue regeneration ability. At present, bacteria elimination, inflammatory response suppression and angiogenesis orderly render an important paradigm for chronic diabetic wound treatment. Herein, smart-responsive multifunctional hydrogels were developed to improve chronic diabetic wound healing, which could quickly respond to the acidic environment of the diabetic wound site and mediate multistage sequential delivery of silver and curcumin-loaded polydopamine nanoparticles (PDA@Ag&Cur NPs) and vascular endothelial growth factor (VEGF). PDA@Ag&Cur NPs and VEGF endowed the hydrogels with antibacterial, anti-inflammatory and angiogenesis performances, respectively. The in vitro and in vivo experiments confirmed that our multistage drug delivery hydrogels could effectively eliminate bacteria, relieve inflammatory response, and induce angiogenesis, hence accelerating the closure of chronic diabetic wounds. In conclusion, we highlighted the importance of multistage manipulation in wound healing and offered a combinatorial therapeutic strategy to sequentially deliver drugs exactly aiming at the dynamic wound healing stages.

摘要

由于慢性糖尿病伤口的微环境恶劣且组织再生能力差,治愈它仍然具有挑战性。目前,消除细菌、抑制炎症反应和促进血管生成有序地成为慢性糖尿病伤口治疗的重要范例。在此,开发了智能响应多功能水凝胶以改善慢性糖尿病伤口愈合,其能够快速响应糖尿病伤口部位的酸性环境,并介导负载银和姜黄素的聚多巴胺纳米颗粒(PDA@Ag&Cur NPs)和血管内皮生长因子(VEGF)的多阶段顺序递送。PDA@Ag&Cur NPs和VEGF分别赋予水凝胶抗菌、抗炎和促血管生成性能。体外和体内实验证实,我们的多阶段药物递送水凝胶可以有效消除细菌、减轻炎症反应并诱导血管生成,从而加速慢性糖尿病伤口的愈合。总之,我们强调了多阶段操作在伤口愈合中的重要性,并提供了一种组合治疗策略,以针对动态伤口愈合阶段精确地顺序递送药物。

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