A biomaterial-based therapy for lower limb ischemia using Sr/Si bioactive hydrogel that inhibits skeletal muscle necrosis and enhances angiogenesis  

作　　者：Ye Yuan Zhaowenbin Zhang Fandi Mo Chen Yang Yiren Jiao Enci Wang Yuchong Zhang Peng Lin Chengkai Hu Weiguo Fu Jiang Chang Lixin Wang 

机构地区：[1]Department of Vascular Surgery,Zhongshan Hospital,Fudan University,180 Fenglin Road,Shanghai,200032,China [2]Department of Vascular Surgery,Zhongshan Xiamen Hospital,Fudan University,668 JinhuRoad,Xiamen,361015,China [3]Joint Centre of Translational Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China [4]Zhejiang Engineering Research Center for Tissue Repair Materials,Wenzhou Institute,University of Chinese Academy of Sciences,Wenzhou,325000,China [5]Shanghai Institute of Ceramics,Chinese Academy of Sciences,1295 Dingxi Road,Shanghai,200050,China

出　　处：《Bioactive Materials》2023年第8期264-278,共15页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(grant number:82270415);Key Project Fund of Natural Science Foundation of Fujian Science and Technology Department(grant number:2021GGB030);Shanghai Municipal Science and Technology Commission Innovation Fund(grant number:22S31904800);Fudan Zhangjiang Clinical Medicine Innovation Fund(grant number:KP7202115);Fujian Province Health Science and Technology Fund(grant number:2021GGB030);the National Natural Science Foundation of China(grant number:81970412);Medical-Industrial Cooperation Project of Zhongshan Hospital Affiliated to Fudan University(grant number:MP2021Q2C018);National Clinical Research Center for Interventional Medicine Fund(grant number:2021-004);Xiamen Municipal Health Science And Technology Program Fund(grant number:3502Z20194034);Zhongshan hospital’s Talents Supporting Plan(grant number:2019ZSGG11);Shanghai Municipal Science and Technology Commission Innovation Fund(grant number:18441902400).

摘　　要：Muscle necrosis and angiogenesis are two major challenges in the treatment of lower-limb ischemic diseases.In this study,a triple-functional Sr/Si-containing bioceramic/alginate composite hydrogel with simultaneous bioactivity in enhancing angiogenesis,regulating inflammation,and inhibiting muscle necrosis was designed to treat lower-limb ischemic diseases.In particular,sodium alginate,calcium silicate and strontium carbonate were used to prepare injectable hydrogels,which was gelled within 10 min.More importantly,this composite hydrogel sustainedly releases bioactive Sr^(2+)and SiO_(3)^(2-) ions within 28 days.The biological activity of the bioactive ions released from the hydrogels was verified on HUVECs,SMCs,C2C12 and Raw 264.7 cells in vitro,and the therapeutic effect of the hydrogel was confirmed using C57BL/6 mouse model of femoral artery ligation in vivo.The results showed that the composite hydrogel stimulated angiogenesis,developed new collateral capillaries,and re-established the blood supply.In addition,the bioactive hydrogel directly promoted the expression of muscle-regulating factors(MyoG and MyoD)to protect skeletal muscle from necrosis,inhibited M1 polarization,and promoted M2 polarization of macrophages to reduce inflammation,thereby protecting skeletal muscle cells and indirectly promoting vascularization.Our results indicate that these bioceramic/alginate composite bioactive hydrogels are effective biomaterials for treating hindlimb ischemia and suggest that biomaterial-based approaches may have remarkable potential in treating ischemic diseases.

关 键 词：Hindlimb ischemic diseases Strontium carbonate and calcium silicate BIOCERAMIC Bioactive hydrogel Muscle necrosis ANGIOGENESIS 

分 类 号：TQ427.26[化学工程] R318[医药卫生—生物医学工程]