title: Engineering a vascularized collagen-β-tricalcium phosphate graft using an electrochemical approach.
abstract: Vascularization of three-dimensional large synthetic grafts for tissue regeneration remains a significant challenge. Here we demonstrate an electrochemical approach, named the cell electrochemical detachment (CED) technique, to form an integral endothelium and use it to prevascularize a collagen-β-tricalcium phosphate (β-TCP) graft. The CED technique electrochemically detached an integral endothelium from a gold-coated glass rod to a collagen-infiltrated, channeled, macroporous β-TCP scaffold, forming an endothelium-lined microchannel containing graft upon removal of the rod. The in vitro results from static and perfusion culture showed that the endothelium robustly emanated microvascular sprouting and prevascularized the entire collagen/β-TCP integrated graft. The in vivo subcutaneous implantation studies showed that the prevascularized collagen/β-TCP grafts established blood flow originating from the endothelium-lined microchannel within a week, and the blood flow covered more areas in the graft over time. In addition, many blood vessels invaded the prevascularized collagen/β-TCP graft and the in vitro preformed microvascular networks anastomosed with the host vasculature, while collagen alone without the support of rigid ceramic scaffold showed less blood vessel invasion and anastomosis. These results suggest a promising strategy for effectively vascularizing large tissue-engineered grafts by integrating multiple hydrogel-based CED-engineered endothelium-lined microchannels into a rigid channeled macroporous scaffold.
authors.affiliation: Department of Orthopedic Surgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Mochizuki
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02139, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: Graduate School of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501 Japan; Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan. Electronic address: fukuda@ynu.ac.jp.
authors.forename: Junji
authors.initials: J
authors.lastname: Fukuda
authors.affiliation: Department of Orthopedic Surgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Materials Science and Engineering, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA. Electronic address: ypyang@stanford.edu.
authors.forename: Yunzhi
authors.initials: Y
authors.lastname: Yang
mesh_terms: D016025:Bone Transplantation / Q000295:instrumentation* / Q000379:methods*; D002130:Calcium Phosphates / Q000737:chemistry*; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D064595:Composite Tissue Allografts; D004563:Electrochemistry / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008422:Materials Testing; D055806:Microvessels / Q000166:cytology / Q000254:growth & development*; D018919:Neovascularization, Physiologic / Q000502:physiology; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D054457:Tissue Scaffolds; D063986:Vascularized Composite Allotransplantation / Q000295:instrumentation
chemical_list: D002130:Calcium Phosphates; C485817:beta-tricalcium phosphate; D003094:Collagen
keywords: Collagen; Electrochemical; Microchannel; Vascularization; β-Tricalcium phosphate