title: Development of an angiogenesis-promoting microvesicle-alginate-polycaprolactone composite graft for bone tissue engineering applications.
abstract: One of the major challenges of bone tissue engineering applications is to construct a fully vascularized implant that can adapt to hypoxic environments in vivo. The incorporation of proangiogenic factors into scaffolds is a widely accepted method of achieving this goal. Recently, the proangiogenic potential of mesenchymal stem cell-derived microvesicles (MSC-MVs) has been confirmed in several studies. In the present study, we incorporated MSC-MVs into alginate-polycaprolactone (PCL) constructs that had previously been developed for bone tissue engineering applications, with the aim of promoting angiogenesis and bone regeneration. MSC-MVs were first isolated from the supernatant of rat bone marrow-derived MSCs and characterized by scanning electron microscopic, confocal microscopic, and flow cytometric analyses. The proangiogenic potential of MSC-MVs was demonstrated by the stimulation of tube formation of human umbilical vein endothelial cells in vitro. MSC-MVs and osteodifferentiated MSCs were then encapsulated with alginate and seeded onto porous three-dimensional printed PCL scaffolds. When combined with osteodifferentiated MSCs, the MV-alginate-PCL constructs enhanced vessel formation and tissue-engineered bone regeneration in a nude mouse subcutaneous bone formation model, as demonstrated by micro-computed tomographic, histological, and immunohistochemical analyses. This MV-alginate-PCL construct may offer a novel, proangiogenic, and cost-effective option for bone tissue engineering.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 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, Shanghai, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Hematology, the Central Hospital of Jingzhou, Jingzhou Hubei, 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, 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, China.
authors.forename: Aiqi
authors.initials: A
authors.lastname: Zhao
authors.affiliation: Department of Hematology, the Central Hospital of Wuhan, Wuhan, 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, China.
authors.forename: Qiubai
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: WenJie
authors.initials: W
authors.lastname: Zhang
keywords: Alginate; Angiogenesis; Bone tissue engineering; Mesenchymal stem cell; Microvesicle; Polycaprolactone