| Title | Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration |
| Authors | Gao, Yike Yuan, Zuoying Yuan, Xiaojing Wan, Zhuo Yu, Yingjie Zhan, Qi Zhao, Yuming Han, Jianmin Huang, Jianyong Xiong, Chunyang Cai, Qing |
| Affiliation | Peking Univ, Natl Ctr Stomatol, Natl Clin Res Ctr Oral Dis,Natl Engn Lab Digital, Dept Pediat Dent,Sch & Hosp Stomatol, Beijing 100081, Peoples R China Peking Univ, Coll Engn, Dept Mech & Engn Sci, Beijing 100871, Peoples R China Beijing Univ Chem Technol, State Key Lab Organ Inorgan Composites, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China Tianjin Univ, Sch Mat Sci & Engn, Tianjin Key Lab Composite & Funct Mat, Tianjin 300072, Peoples R China Peking Univ, Dent Med Devices Testing Ctr, Dent Mat Lab, Sch & Hosp Stomatol, Beijing 100081, Peoples R China Univ Chinese Acad Sci, Wenzhou Inst, Oujiang Lab, Wenzhou 325000, Zhejiang, Peoples R China |
| Keywords | EXFOLIATED DECIDUOUS TEETH STEM-CELLS EXTRACELLULAR VESICLES STRATEGIES REPAIR PULP |
| Issue Date | Aug-2022 |
| Publisher | BIOACTIVE MATERIALS |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/642789 |
| DOI | 10.1016/j.bioactmat.2022.01.041 |
| Indexed | SCI(E) |
| Appears in Collections: | 口腔医院 工学院 |
