title: Implanted cell-dense prevascularized tissues develop functional vasculature that supports reoxygenation after thrombosis.
abstract: Achieving adequate vascularization within implanted engineered tissues is a significant obstacle to maintaining viability and functionality. In vitro prevascularization of engineered tissues has been explored as a potential solution to this challenge. The traditional paradigm of in vitro prevascularization is to implant an engineered tissue with a preformed vascular network that is perfused after anastomosis with the host circulation. We investigated the efficacy of this strategy by implanting cell-dense prevascularized tissues created via cell-mediated contraction and composed of collagen and a collagen-fibrin mixture into dorsal window chambers surgically prepared on immunocompromised mice. We found that host-implant anastomosis takes place in 2-6 days and that perfusion of vessels within the implants is subsequently restricted by thrombosis. However, by day 7, a functional vascular network composed of host and implant vessels developed. Prevascularization enhanced intra-implant pO2 significantly as early as 2 days postimplantation, reaching a maximum of 55 mmHg by day 8, which was significantly greater than the maximum within cellularized control tissues (18 mmHg). By day 14, collagen tissues supported ∼ 0.51 × 10(9) implanted and host-derived cells per mL. Our findings elucidate key features of in vitro prevascularization that can be used toward the design of larger and more functionally complex engineered tissues.
authors.affiliation: 1 Department of Biomedical Engineering, University of California , Irvine, Irvine, California.
authors.forename: Sean M
authors.initials: SM
authors.lastname: White
authors.forename: Chelsea R
authors.initials: CR
authors.lastname: Pittman
authors.forename: Ryan
authors.initials: R
authors.lastname: Hingorani
authors.forename: Rajan
authors.initials: R
authors.lastname: Arora
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Esipova
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Vinogradov
authors.forename: Christopher C W
authors.initials: CC
authors.lastname: Hughes
authors.forename: Bernard
authors.initials: B
authors.lastname: Choi
authors.forename: Steven C
authors.initials: SC
authors.lastname: George
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000254:growth & development*; D002452:Cell Count; D002478:Cells, Cultured; D064595:Composite Tissue Allografts / Q000098:blood supply / Q000254:growth & development* / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology / Q000637:transplantation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D018919:Neovascularization, Physiologic; D010100:Oxygen / Q000378:metabolism*; D013927:Thrombosis / Q000503:physiopathology* / Q000628:therapy*; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods
chemical_list: D010100:Oxygen