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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...

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Autores principales: Gao, Yike, Yuan, Zuoying, Yuan, Xiaojing, Wan, Zhuo, Yu, Yingjie, Zhan, Qi, Zhao, Yuming, Han, Jianmin, Huang, Jianyong, Xiong, Chunyang, Cai, Qing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2022
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.
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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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