title: Extracellular Vesicle-functionalized Decalcified Bone Matrix Scaffolds with Enhanced Pro-angiogenic and Pro-bone Regeneration Activities.
abstract: Vascularization is crucial for bone regeneration after the transplantation of tissue-engineered bone grafts in the clinical setting. Growing evidence suggests that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are potently pro-angiogenic both in vitro and in vivo. In the current study, we fabricated a novel EV-functionalized scaffold with enhanced pro-angiogenic and pro-bone regeneration activities by coating decalcified bone matrix (DBM) with MSC-derived EVs. EVs were harvested from rat bone marrow-derived MSCs and the pro-angiogenic potential of EVs was investigated in vitro. DBM scaffolds were then coated with EVs, and the modification was verified by scanning electron microscopy and confocal microscopy. Next, the pro-angiogenic and pro-bone regeneration activities of EV-modified scaffolds were evaluated in a subcutaneous bone formation model in nude mice. Micro-computed tomography scanning analysis showed that EV-modified scaffolds with seeded cells enhanced bone formation. Enhanced bone formation was confirmed by histological analysis. Immunohistochemical staining for CD31 proved that EV-modified scaffolds promoted vascularization in the grafts, thereby enhancing bone regeneration. This novel scaffold modification method provides a promising way to promote vascularization, which is essential for bone tissue engineering.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, Shanghai 200011, P. R. China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Hematology, the Central Hospital of Jingzhou, Jingzhou 434020, P. R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Lei
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P. R. China.
authors.forename: Aiqi
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Department of Hematology, the Central Hospital of Wuhan, Wuhan 430012, P. R. China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P. R. China.
authors.forename: Qiubai
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, Shanghai 200011, P. R. China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, Shanghai 200011, P. R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Jie Zhang
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P. R. China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000098:blood supply / Q000378:metabolism / Q000502:physiology*; D001861:Bone Regeneration; D002113:Calcification, Physiologic; D002478:Cells, Cultured; D000067128:Extracellular Vesicles / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D055114:X-Ray Microtomography