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Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration
Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated regenerative potential for cell-free bone tissue engineering, nevertheless, certain challenges, including the confined therapeutic potency of exosomes and ineffective delivery method, are still persisted. Here, we confirmed that h...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
KeAi Publishing
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964815/ https://www.ncbi.nlm.nih.gov/pubmed/35386817 http://dx.doi.org/10.1016/j.bioactmat.2022.01.041 |
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author | Gao, Yike Yuan, Zuoying Yuan, Xiaojing Wan, Zhuo Yu, Yingjie Zhan, Qi Zhao, Yuming Han, Jianmin Huang, Jianyong Xiong, Chunyang Cai, Qing |
author_facet | Gao, Yike Yuan, Zuoying Yuan, Xiaojing Wan, Zhuo Yu, Yingjie Zhan, Qi Zhao, Yuming Han, Jianmin Huang, Jianyong Xiong, Chunyang Cai, Qing |
author_sort | Gao, Yike |
collection | PubMed |
description | Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated regenerative potential for cell-free bone tissue engineering, nevertheless, certain challenges, including the confined therapeutic potency of exosomes and ineffective delivery method, are still persisted. Here, we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth (SHEDs) via comprehensive proteomics analysis, and the corresponding hypoxic exosomes (H-Exo) exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion, VEGF signaling pathway, and thyroid hormone synthesis. Then, we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection. This platform is based on a simple adsorbing technique, where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide) (PLGA) microspheres with bioinspired polydopamine (PDA) coating (PMS-PDA microspheres). The PMS-PDA microspheres could effectively adsorb exosomes, show sustained release of H-Exo for 21 days with high bioactivity, and induce vascularized bone regeneration in 5-mm rat calvarial defect. These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration, hence facilitating the clinical translation of exosome-based therapy. |
format | Online Article Text |
id | pubmed-8964815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | KeAi Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-89648152022-04-05 Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration Gao, Yike Yuan, Zuoying Yuan, Xiaojing Wan, Zhuo Yu, Yingjie Zhan, Qi Zhao, Yuming Han, Jianmin Huang, Jianyong Xiong, Chunyang Cai, Qing Bioact Mater Article Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated regenerative potential for cell-free bone tissue engineering, nevertheless, certain challenges, including the confined therapeutic potency of exosomes and ineffective delivery method, are still persisted. Here, we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth (SHEDs) via comprehensive proteomics analysis, and the corresponding hypoxic exosomes (H-Exo) exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion, VEGF signaling pathway, and thyroid hormone synthesis. Then, we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection. This platform is based on a simple adsorbing technique, where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide) (PLGA) microspheres with bioinspired polydopamine (PDA) coating (PMS-PDA microspheres). The PMS-PDA microspheres could effectively adsorb exosomes, show sustained release of H-Exo for 21 days with high bioactivity, and induce vascularized bone regeneration in 5-mm rat calvarial defect. These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration, hence facilitating the clinical translation of exosome-based therapy. KeAi Publishing 2022-02-01 /pmc/articles/PMC8964815/ /pubmed/35386817 http://dx.doi.org/10.1016/j.bioactmat.2022.01.041 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Gao, Yike Yuan, Zuoying Yuan, Xiaojing Wan, Zhuo Yu, Yingjie Zhan, Qi Zhao, Yuming Han, Jianmin Huang, Jianyong Xiong, Chunyang Cai, Qing Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration |
title | Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration |
title_full | Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration |
title_fullStr | Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration |
title_full_unstemmed | Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration |
title_short | Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration |
title_sort | bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964815/ https://www.ncbi.nlm.nih.gov/pubmed/35386817 http://dx.doi.org/10.1016/j.bioactmat.2022.01.041 |
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