Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration

Yike Gao; Zuoying Yuan; Xiaojing Yuan; Zhuo Wan; Yingjie Yu; Qi Zhan; Yuming Zhao; Jianmin Han; Jianyong Huang; Chunyang Xiong; Qing Cai

Bioactive Materials (Aug 2022)

Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration

Yike Gao,
Zuoying Yuan,
Xiaojing Yuan,
Zhuo Wan,
Yingjie Yu,
Qi Zhan,
Yuming Zhao,
Jianmin Han,
Jianyong Huang,
Chunyang Xiong,
Qing Cai

Affiliations

Yike Gao: Department 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
Zuoying Yuan: Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China
Xiaojing Yuan: Department 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
Zhuo Wan: Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China
Yingjie Yu: State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China
Qi Zhan: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, China
Yuming Zhao: Department 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. .
Jianmin Han: Dental Medical Devices Testing Center, Dental Materials Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, China
Jianyong Huang: Department of Mechanics and Engineering Science, College of Engineering, Peking University, Beijing, 100871, China
Chunyang Xiong: Department 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..
Qing Cai: State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China; Corresponding author. .

Journal volume & issue: Vol. 14
pp. 377 – 388

Abstract

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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.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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