Chung, Haeun Choi, Jung-Kyun Hong, Changgi Lee, Youngseop Hong, Ki Hyun Oh, Seung Ja Kim, Jeongmin Song, Soo-Chang Kim, Jong-Wan Kim, Sang-Heon 2024-05-30T08:30:46Z 2024-05-30T08:30:46Z 2024-05-30 2024-04 https://pubs.kist.re.kr/handle/201004/149954 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 x 20 mu m) 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 CMGhASCs as promising therapeutics to treat CLI. English Elsevier A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair Article 10.1016/j.bioactmat.2023.12.008 1 Bioactive Materials, v.34, pp.80 - 97 Bioactive Materials 34 80 97 Y scie scopus 001225697500001 2-s2.0-85180450685 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article ENHANCE ANGIOGENESIS HYALURONIC-ACID SURVIVAL THERAPY VIVO Collagen microgel 3D cell culture Critical limb ischemia Regenerative medicine Stem cell therapy