A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair  

作　　者：Haeun Chung Jung-Kyun Choi Changgi Hong Youngseop Lee Ki Hyun Hong Seung Ja Oh Jeongmin Kim Soo-Chang Song Jong-Wan Kim Sang-Heon Kim 

机构地区：[1]Center for Biomaterials,Biomedical Research Institute,Korea Institute of Science and Technology(KIST),Seoul,02792,Republic of Korea [2]Division of Bio-Medical Science and Technology,KIST School,University of Science and Technology,Seoul,02792,Republic of Korea [3]Department of Applied Bioengineering,Graduate School of Convergence Science and Technology,Seoul National University,Seoul,08826,Republic of Korea [4]Research Institute for Convergence Science,Seoul National University,Seoul,08826,Republic of Korea [5]Department of Genetics and Biotechnology,College of Life Sciences,Kyung Hee University,Yongin-si,Gyeonggi-do,17104,Republic of Korea [6]S.Biomedics Co.,Ltd.,Seoul,04797,Republic of Korea

出　　处：《Bioactive Materials》2024年第4期80-97,共18页生物活性材料（英文）

基　　金：supported by a grant from the Korean Fund for Regenerative Medicine,funded by the Ministry of Science and ICT,and the Ministry of Health&Welfare of Korea[22C0620L1-11].

摘　　要：Critical limb ischemia(CLI)is a devastating disease characterized by the progressive blockage of blood vessels.Although the paracrine effect of growth factors in stem cell therapy made it a promising angiogenic therapy for CLI,poor cell survival in the harsh ischemic microenvironment limited its efficacy.Thus,an imperative need exists for a stem-cell delivery method that enhances cell survival.Here,a collagen microgel(CMG)cell-delivery scaffold(40×20μm)was fabricated via micro-fragmentation from collagen-hyaluronic acid polyionic complex to improve transplantation efficiency.Culturing human adipose-derived stem cells(hASCs)with CMG enabled integrin receptors to interact with CMG to form injectable 3-dimensional constructs(CMG-hASCs)with a microporous microarchitecture and enhanced mass transfer.CMG-hASCs exhibited higher cell survival(p<0.0001)and angiogenic potential in tube formation and aortic ring angiogenesis assays than cell aggregates.Injection of CMG-hASCs intramuscularly into CLI mice increased blood perfusion and limb salvage ratios by 40%and 60%,respectively,compared to cell aggregate-treated mice.Further immunofluorescent analysis revealed that transplanted CMG-hASCs have greater muscle regenerative and angiogenic potential,with enhanced cell survival than cell aggregates(p<0.05).Collectively,we propose CMG as a cell-assembling platform and CMG-hASCs as promising therapeutics to treat CLI.

关 键 词：Regenerative medicine Stem cell therapy Collagen microgel 3D cell culture Critical limb ischemia 

分 类 号：R318.08[医药卫生—生物医学工程]