详细信息

Adipose-derived stem cell/FGF19-loaded microfluidic hydrogel microspheres for synergistic restoration of critical ischemic limb    

文献类型:期刊文献

中文题名:Adipose-derived stem cell/FGF19-loaded microfluidic hydrogel microspheres for synergistic restoration of critical ischemic limb

作者:Ruihan Wang[1,2,3];Fangqian Wang[4,5];Shan Lu[1,2,3];Bin Gao[1,2,3];Yuanqing Kan[1,2,3];Tong Yuan[1,2,3];Yisheng Xu[6];Chen Yuan[6];Daqiao Guo[1,2,3];Weiguo Fu[1,2,3];Xiaohua Yu[4,5];Yi Si[1,2,3]

机构:[1]Department of Vascular Surgery,Zhongshan Hospital Fudan University,Shanghai,200032,PR China;[2]Institute of Vascular Surgery,Fudan University,Shanghai,200032,PR China;[3]National Clinical Research Center for Interventional Medicine,Shanghai,200032,PR China;[4]Department of Orthopedics,The Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou,310009,Zhejiang,PR China;[5]Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province,Hangzhou,310000,Zhejiang,PR China;[6]State Key Laboratory of Chemical Engineering,East China University of Science and Technology,Shanghai,200237,China

年份:2023

期号:9

起止页码:394

中文期刊名:Bioactive Materials

外文期刊名:生物活性材料(英文)

收录:Scopus;CSCD:【CSCD2023_2024】;PubMed;

基金:supported by the National Natural Science Foundation of China(grant number 8207021027);Shanghai Clinical Research Center for Interventional Medicine(grant number 19MC1910300);Shanghai Science and Technology Commission(grant numbers 19441906600,21S31904800).

语种:英文

中文关键词:Microfluidic technology;Stem cell;Cytokine;Porous microspheres;Ischemic limb salvage

摘要:The efficacy of stem cell therapy is substantially compromised due to low cell survival rate and poor local retention post-delivery. These issues drastically limit the application of stem cells for ischemic limb therapy, which requires effective blood perfusion and skeletal muscle regeneration. Herein, based on microfluidic technology, an integrated stem cell and cytokine co-delivery system designed for functional ischemic limb salvage was constructed by first incorporating the myogenic cytokine, fibroblast growth factor 19 (FGF19), into microspheres composed of methacrylate gelatin (GelMA). Then adipose-derived stem cells (ADSCs) were highly absorbed into the porous structure of the microspheres, overcoming the insufficient loading efficiency and activities by conventional encapsulation strategy. The fabricated ADSCs/FGF19@μsphere system demonstrated a uniform size of about 180 μm and a highly porous structure with pore sizes between 20 and 40 μm. The resultant system allowed high doses of ADSCs to be precisely engrafted in the lesion and to survive, and achieved sustained FGF19 release in the ischemic region to facilitate myoblast recruitment and differentiation and myofibrils growth. Furthermore, the combination of ADSCs and FGF19 exhibited a positive synergistic effect which substantially improved the therapeutic benefit of angiogenesis and myogenesis, both in vitro and in vivo. In summary, a stem cell and cytokine co-delivery system with the properties of easy preparation and minimal invasiveness was designed to ensure highly efficient cell delivery, sustained cytokine release, and ultimately realizes effective treatment of ischemic limb regeneration.

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