title: Human Skin Constructs with Spatially Controlled Vasculature Using Primary and iPSC-Derived Endothelial Cells.
abstract: Vascularization of engineered human skin constructs is crucial for recapitulation of systemic drug delivery and for their long-term survival, functionality, and viable engraftment. In this study, the latest microfabrication techniques are used and a novel bioengineering approach is established to micropattern spatially controlled and perfusable vascular networks in 3D human skin equivalents using both primary and induced pluripotent stem cell (iPSC)-derived endothelial cells. Using 3D printing technology makes it possible to control the geometry of the micropatterned vascular networks. It is verified that vascularized human skin equivalents (vHSEs) can form a robust epidermis and establish an endothelial barrier function, which allows for the recapitulation of both topical and systemic delivery of drugs. In addition, the therapeutic potential of vHSEs for cutaneous wounds on immunodeficient mice is examined and it is demonstrated that vHSEs can both promote and guide neovascularization during wound healing. Overall, this innovative bioengineering approach can enable in vitro evaluation of topical and systemic drug delivery as well as improve the potential of engineered skin constructs to be used as a potential therapeutic option for the treatment of cutaneous wounds.
authors.affiliation: Department of Dermatology, Columbia University Medical Center, NY, 10032, USA.
authors.forename: Hasan E
authors.initials: HE
authors.lastname: Abaci
authors.affiliation: Department of Dermatology, Columbia University Medical Center, NY, 10032, USA.
authors.forename: Zongyou
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Dermatology, Columbia University Medical Center, NY, 10032, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Coffman
authors.affiliation: Department of Biomedical Engineering, Columbia University, NY, 10032, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Gillette
authors.affiliation: Department of Biomedical Engineering, Columbia University, NY, 10032, USA.
authors.forename: Wen-Han
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Columbia University, NY, 10032, USA.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Sia
authors.affiliation: Department of Dermatology, Columbia University Medical Center, NY, 10032, USA.|Department of Genetics and Development, Columbia University Medical Center, NY, 10032, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D064593:Heterografts; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic; D012867:Skin / Q000098:blood supply* / Q000293:injuries* / Q000378:metabolism; D014945:Wound Healing
keywords: engineered skin; iPSC; microfluidics; patterning; vasculature