A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair
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...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2024-04-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X23004048 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Haeun Chung |
| collection | DOAJ |
| description | 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 × 20 μm) 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. |
| first_indexed | 2024-03-08T05:54:12Z |
| format | Article |
| id | doaj.art-072e01d968e34ec392dc8d7eda88919c |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-03-08T05:54:12Z |
| publishDate | 2024-04-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-072e01d968e34ec392dc8d7eda88919c2024-02-05T04:32:00ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-04-01348097A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repairHaeun Chung0Jung-Kyun Choi1Changgi Hong2Youngseop Lee3Ki Hyun Hong4Seung Ja Oh5Jeongmin Kim6Soo-Chang Song7Jong-Wan Kim8Sang-Heon Kim9Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology, Seoul, 02792, Republic of KoreaCenter for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology, Seoul, 02792, Republic of KoreaDepartment of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea; Research Institute for Convergence Science, Seoul National University, Seoul, 08826, Republic of KoreaDepartment of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of KoreaCenter for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of KoreaDepartment of Genetics and Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do, 17104, Republic of KoreaDepartment of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea; Research Institute for Convergence Science, Seoul National University, Seoul, 08826, Republic of KoreaCenter for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology, Seoul, 02792, Republic of KoreaS.Biomedics Co., Ltd., Seoul, 04797, Republic of KoreaCenter for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology, Seoul, 02792, Republic of Korea; Corresponding author. Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.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 × 20 μm) 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.http://www.sciencedirect.com/science/article/pii/S2452199X23004048Regenerative medicineStem cell therapyCollagen microgel3D cell cultureCritical limb ischemia |
| spellingShingle | 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 A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair Bioactive Materials Regenerative medicine Stem cell therapy Collagen microgel 3D cell culture Critical limb ischemia |
| title | A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair |
| title_full | A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair |
| title_fullStr | A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair |
| title_full_unstemmed | A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair |
| title_short | A micro-fragmented collagen gel as a cell-assembling platform for critical limb ischemia repair |
| title_sort | micro fragmented collagen gel as a cell assembling platform for critical limb ischemia repair |
| topic | Regenerative medicine Stem cell therapy Collagen microgel 3D cell culture Critical limb ischemia |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X23004048 |
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