Macrophage metabolism reprogramming EGCG-Cu coordination capsules delivered in polyzwitterionic hydrogel for burn wound healing and regeneration  

作　　者：Qinghua Li Huijuan Song Shuangyang Li Pengbo Hu Chuangnian Zhang Ju Zhang Zujian Feng Deling Kong Weiwei Wang Pingsheng Huang 

机构地区：[1]Tianjin Key Laboratory of Biomaterial Research,Institute of Biomedical Engineering,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin,300192,China [2]Institute of Radiation Medicine,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin,300192,China [3]Department of Polymer Science and Engineering,Key Laboratory of Systems Bioengineering,School of Chemical Engineering and Technology,Tianjin University,Tianjin,300072,China [4]Emergency Department of Binzhou Medical University Hospital,Binzhou,Shandong Province,256600,China [5]State Key Laboratory of Medicinal Chemical Biology,College of Life Sciences,Nankai University,Tianjin,300071,China

出　　处：《Bioactive Materials》2023年第11期251-264,共14页生物活性材料（英文）

基　　金：the National Natural Science Foundation of China(No.82272162,82001954);Fundamental Research Funds for the Central Universities (3332021067, 2019PT350005);Natural Science Fund for Distinguished Young Scholars of Tianjin (21JCJQJC00020);CAMS Innovation Fund for Medical Sciences (2021-I2M-1-052, 2021- I2M-1-058, 2021-I2M-1-065);Tianjin Innovation and Promotion Plan Key Innovation Team of Implantable and Interventional Biomedical Materials.

摘　　要：Excessive reactive oxygen species(ROS)at severe burn injury sites may promote metabolic reprogramming of macrophages to induce a deteriorative and uncontrolled inflammation cycle,leading to delayed wound healing and regeneration.Here,a novel bioactive,anti-fouling,flexible polyzwitterionic hydrogel encapsulated with epigallocatechin gallate(EGCG)-copper(Cu)capsules(termed as EGCG-Cu@CBgel)is engineered for burn wound management,which is dedicated to synergistically exerting ROS-scavenging,immune metabolic regulation and pro-angiogenic effects.EGCG-Cu@CBgel can scavenge ROS to normalize intracellular redox homeostasis,effectively relieving oxidative damages and blocking proinflammatory signal transduction.Importantly,EGCG-Cu can inhibit the activity of hexokinase and phosphofructokinase,alleviate accumulation of pyruvate and convert it to acetyl coenzyme A(CoA),whereby inhibits glycolysis and normalizes tricarboxylic acid(TCA)cycle.Additionally,metabolic reprogramming of macrophages by EGCG-Cu downregulates M1-type polarization and the expression of proinflammatory cytokines both in vitro and in vivo.Meanwhile,copper ions(Cu^(2+))released from the hydrogel facilitate angiogenesis.EGCG-Cu@CBgel significantly accelerates the healing of severe burn wound via promoting wound closure,weakening tissue-damaging inflammatory responses and enhancing the remodeling of pathological structure.Overall,this study demonstrates the great potential of bioactive hydrogel dressing in treating burn wounds without unnecessary secondary damage to newly formed skin,and highlights the importance of immunometabolism modulation in tissue repair and regeneration.

关 键 词：ROS scavenging Hydrogel dressing EGCG-Cu capsule Metabolic reprogramming Burn wound healing 

分 类 号：R318[医药卫生—生物医学工程] TB3[医药卫生—基础医学]