Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure

作     者：Yuanyuan Jin Jiabin Zhang Yanteng Xu Ke Yi Fenfang Li Huicong Zhou Haixia Wang Hon Fai Chan Yeh-Hsing Lao Shixian Lv Yu Tao Mingqiang Li 

作者机构：Laboratory of Biomaterials and Translational MedicineCenter for NanomedicineThe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou510630China Guangdong Provincial Key Laboratory of Liver Disease ResearchGuangzhou510630China School of Materials Science and EngineeringPeking UniversityBeijing100871China Institute for Tissue Engineering and Regenerative MedicineSchool of Biomedical ScienceThe Chinese University of Hong Kong999077Hong KongChina Department of Pharmaceutical SciencesUniversity at BuffaloThe State University of New YorkBuffaloNY14214USA 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2023年第28卷第10期

页      面：112-131页

核心收录：

学科分类：1002[医学-临床医学] 07[理学] 070205[理学-凝聚态物理] 08[工学] 080501[工学-材料物理与化学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 0805[工学-材料科学与工程（可授工学、理学学位）] 0702[理学-物理学] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China(2019YFA0111300) the National Natural Science Foundation of China(22277155,32001012) the Science and Technology Program of Guangzhou(202102010225,202102010217) the Guangdong Provincial Pearl Talents Program(2019QN01Y131) Guangdong Basic and Applied Basic Research Foundation(2022A1515110685,2023A1515011067) the China Postdoctoral Science Foundation(2020M683060) the Talent Introduction Program of Postdoctoral International Exchange Program(YJ20200313) the Thousand Talents Plan,and the China Primary Health Care Foundation(2022-003) 

主　　题：Acute liver failure Nanozyme Hepatocyte-like cells Human adipose-derived mesenchymal stem/stromal cells Electrospun nanofiber 

摘      要：Reactive oxygen species(ROS)-associated oxidative stress,inflammation storm,and massive hepatocyte necrosis are the typical manifestations of acute liver failure(ALF),therefore specific therapeutic interventions are essential for the devastating ***,we developed a platform consisting of versatile biomimetic copper oxide nanozymes(Cu NZs)-loaded PLGA nanofibers(Cu NZs@PLGA nanofibers)and decellularized extracellular matrix(dECM)hydrogels for delivery of human adipose-derived mesenchymal stem/stromal cells-derived hepatocyte-like cells(hADMSCs-derived HLCs)(HLCs/Cu NZs@fiber/dECM).Cu NZs@PLGA nanofibers could conspicuously scavenge excessive ROS at the early stage of ALF,and reduce the massive accumulation of pro-inflammatory cytokines,herein efficiently preventing the deterioration of hepatocytes ***,Cu NZs@PLGA nanofibers also exhibited a cytoprotection effect on the transplanted ***,HLCs with hepatic-specific biofunctions and anti-inflammatory activity acted as a promising alternative cell source for ALF *** dECM hydrogels further provided the desirable 3D environment and favorably improved the hepatic functions of *** addition,the pro-angiogenesis activity of Cu NZs@PLGA nanofibers also facilitated the integration of the whole implant with the host ***,HLCs/Cu NZs@fiber/dECM performed excellent synergistic therapeutic efficacy on ALF *** strategy using Cu NZs@PLGA nanofiber-reinforced dECM hydrogels for HLCs in situ delivery is a promising approach for ALF therapy and shows great potential for clinical translation.