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Injectable conductive gelatin methacrylate/oxidized dextran hydrogel encapsulating umbilical cord mesenchymal stem cells for myocardial infarction treatment

查看全文 作　　者：Shuoji [1]Zhu;Changjiang [1]Yu;Nanbo [1]Liu;Mingyi [1]Zhao;Zerui [1]Chen;Jian [1]Liu;Ge [1]Li;Huanlei [1]Huang;Huiming [1]Guo;Tucheng [1]Sun;Jimei [1]Chen;Jian [1]Zhuang;Ping [1]Zhu 高影响力作者 机构地区：[1]Guangdong Cardiovascular Institute,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou,510100,China高影响力机构 出　　处：《Bioactive Materials》索引2022年第7卷第7期,共16页高影响力期刊 基　　金：This work was supported by National Key Research and Development Program of China(2018YFA0108700,2017YFA0105602);NSFC Projects of International Cooperation and Exchanges(81720108004);National Natural Science Foundation of China(81974019);the Research Team Project of Natural Science Foundation of Guangdong Province of China(2017A030312007);the key program of guangzhou science research plan(201904020047);the Special Project of Dengfeng Program of Guangdong Provincial People’s Hospital(DFJH201812,KJ012019119,KJ012019423). 摘　　要：Umbilical cord mesenchymal stem cells(UCMSCs)transplantation has been proposed as a promising treatment modality for myocardial infarction(MI),but the low retention rate remains a considerable challenge.Injectable natural polymer hydrogels with conductivity ability are highly desirable as cell delivery vehicles to repair infarct myocardium and restore the cardiac function.In this work,we developed a hydrogel system based on gelatin methacrylate(GelMA)and oxidized dextran(ODEX)as cell delivery vehicles for MI.And dopamine could be used as a reductant of graphene oxide(GO)to form reductive GO(rGO).By adjusting the amount of rGO,the conductivity of hydrogels with 0.5 mg/mL rGO concentration(≈10^(-4)S/cm)was similar to that of natural heart tissue.In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell delivery ability of UCMSCs.More importantly,GelMA-O5/rGO hydrogel could promote UCMSCs growth and proliferation,improve the myocardial differentiation ability of UCMSCs,and up-regulate the expression of cTnI and Cx43.Further in vivo experiments demonstrated that GelMA-O5/rGO/UCMSCs Hydrogel could significantly improve the ejection fraction(EF)of rats and significantly reduce myocardial infarct area compared to PBS group,promote the survival of UCMSCs,enhance the expression level of cTnI and Cx43,and decrease the expression level of caspase-3.The findings of this study suggested that the injectable conductive GelMA-O5/rGO hydrogel encapsulating UCMSCs could improve damaged myocardial tissue and reconstruct myocardial function,which will be a promising therapeutic strategy for cardiac repair. 关 键 词：GelMA Oxidized dextran Conductivity Stem cell therapy Myocardial infarction
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