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 

机构地区：[1]Laboratory of Biomaterials and Translational Medicine,Center for Nanomedicine,The Third Affiliated Hospital,Sun Yat-sen University,Guangzhou,510630,China [2]Guangdong Provincial Key Laboratory of Liver Disease Research,Guangzhou,510630,China [3]School of Materials Science and Engineering,Peking University,Beijing,100871,China [4]Institute for Tissue Engineering and Regenerative Medicine,School of Biomedical Science,The Chinese University of Hong Kong,999077,Hong Kong,China [5]Department of Pharmaceutical Sciences,University at Buffalo,The State University of New York,Buffalo,NY,14214,USA

出　　处：《Bioactive Materials》2023年第10期112-131,共20页生物活性材料（英文）

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).

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 disease.Here,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 necrosis.Moreover,Cu NZs@PLGA nanofibers also exhibited a cytoprotection effect on the transplanted HLCs.Meanwhile,HLCs with hepatic-specific biofunctions and anti-inflammatory activity acted as a promising alternative cell source for ALF therapy.The dECM hydrogels further provided the desirable 3D environment and favorably improved the hepatic functions of HLCs.In addition,the pro-angiogenesis activity of Cu NZs@PLGA nanofibers also facilitated the integration of the whole implant with the host liver.Hence,HLCs/Cu NZs@fiber/dECM performed excellent synergistic therapeutic efficacy on ALF mice.This 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.

关 键 词：Acute liver failure Nanozyme Hepatocyte-like cells Human adipose-derived mesenchymal stem/stromal cells Electrospun nanofiber 

分 类 号：TB383.1[一般工业技术—材料科学与工程] R575.3[医药卫生—消化系统]