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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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2022-08-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X22000561 |
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| author | Yike Gao Zuoying Yuan Xiaojing Yuan Zhuo Wan Yingjie Yu Qi Zhan Yuming Zhao Jianmin Han Jianyong Huang Chunyang Xiong Qing Cai |
| author_facet | Yike Gao Zuoying Yuan Xiaojing Yuan Zhuo Wan Yingjie Yu Qi Zhan Yuming Zhao Jianmin Han Jianyong Huang Chunyang Xiong Qing Cai |
| author_sort | Yike Gao |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T01:11:40Z |
| format | Article |
| id | doaj.art-f4b81ea56e2e4789a19117914e7d7671 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:36:15Z |
| publishDate | 2022-08-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-f4b81ea56e2e4789a19117914e7d76712024-04-16T17:16:33ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-08-0114377388Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regenerationYike Gao0Zuoying Yuan1Xiaojing Yuan2Zhuo Wan3Yingjie Yu4Qi Zhan5Yuming Zhao6Jianmin Han7Jianyong Huang8Chunyang Xiong9Qing Cai10Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, ChinaDepartment of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, ChinaDepartment of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, ChinaState Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, ChinaTianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, China; Corresponding author. .Dental Medical Devices Testing Center, Dental Materials Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, ChinaDepartment of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, ChinaDepartment of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China; Wenzhou Institute, University of Chinese Academy of Sciences, Oujiang Laboratory, Wenzhou, Zhejiang, 325000, China; Corresponding author. Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China..State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China; Corresponding author. .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.http://www.sciencedirect.com/science/article/pii/S2452199X22000561Hypoxic exosomesStem cells from human exfoliated deciduous teethPorous microsphereSustained releaseVascularized bone regeneration |
| spellingShingle | Yike Gao Zuoying Yuan Xiaojing Yuan Zhuo Wan Yingjie Yu Qi Zhan Yuming Zhao Jianmin Han Jianyong Huang Chunyang Xiong Qing Cai Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration Bioactive Materials Hypoxic exosomes Stem cells from human exfoliated deciduous teeth Porous microsphere Sustained release 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 | Hypoxic exosomes Stem cells from human exfoliated deciduous teeth Porous microsphere Sustained release Vascularized bone regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X22000561 |
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