dECM restores macrophage immune homeostasis and alleviates iron overload to promote DTPI healing  

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作  者:Ju Zhang Ruijuan Si Yu Gao Hui Shan Qi Su Zujian Feng Pingsheng Huang Deling Kong Weiwei Wang 

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,Tianjin300192,China [2]School of Nursing,Qingdao University,Ningde Road,Shinan District,Qingdao,Shandong,266071,China [3]Cancer Hospital of Tianjin Medical University,North Huanhu West Road,Tianjin,China [4]The Affliated Hospital of Qingdao University,16 Jjiangsu Road,Shinan District,Qingdao,China 5NankaiUniver aniin300071.China

出  处:《Regenerative Biomaterials》2024年第2期100-113,共14页再生生物材料(英文版)

基  金:supported by the National Natural Science Foundation of China(81701838);the Natural Science Foundation of Shandong(ZR2022MH037).

摘  要:Due to its highly insidious and rapid progression,deep tissue pressure injury(DTPI)is a clinical challenge.Our previous study found that DTPI may be a skeletal muscle injury dominated by macrophage immune dysfunction due to excessive iron accu-mulation.Decellularized extracellular matrix(dECM)hydrogel promotes skeletal muscle injury repair.However,its role in po-larizing macrophages and regulating iron metabolism in DTPI remains unclear.Here,porcine dECM hydrogel was prepared,and its therapeutic function and mechanism in repairing DTPI were investigated.The stimulus of dECM hydrogel toward RAW264.7 cells resulted in a significantly higher percentage of CD2o6+macrophages and notably decreased intracellular divalent iron levels.In mice DTPI model,dECM hydrogel treatment promoted M1 to M2 macrophage conversion,improved iron metabolism and reduced oxidative stress in the early stage of DTPI.In the remodeling phase,the dECM hydrogel remarkably enhanced revascularization and accelerated skeletal muscle repair.Furthermore,the immunomodulation of dEcM hydrogels in vivo was mainly involved in the P13k/Akt signaling pathway,as revealed by GO and KEGG pathway analysis,which may ameliorate the iron deposition and promote the healing of DTPI.Our findings indicate that dECM hydrogel is promising in skeletal muscle repair,inflammation resolution and tissue injury healing by effectively restoring macrophage immune homeostasis and normalizing iron metabolism.

关 键 词:Deep tissue pressure injury HYDROGEL IMMUNOMODULATION tissue repair 

分 类 号:O64[理学—物理化学]

 

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