Human Skin Constructs with Spatially Controlled Vasculature Using Primary and iPSC-Derived Endothelial Cells

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 mi...

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Veröffentlicht in:Advanced healthcare materials 2016-07, Vol.5 (14), p.1800-1807
Hauptverfasser: Abaci, Hasan E., Guo, Zongyou, Coffman, Abigail, Gillette, Brian, Lee, Wen-han, Sia, Samuel K., Christiano, Angela M.
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container_end_page 1807
container_issue 14
container_start_page 1800
container_title Advanced healthcare materials
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creator Abaci, Hasan E.
Guo, Zongyou
Coffman, Abigail
Gillette, Brian
Lee, Wen-han
Sia, Samuel K.
Christiano, Angela M.
description 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. Human skin equivalents with perfusable and preorganized vasculature are developed using both primary‐ and induced‐pluripotent‐stem‐cell‐derived endothelial cells. The vascularized human skin equivalents, which have a robust epidermis and endothelial barrier function, enable the study of systemic delivery of drugs in vitro. In addition, they both promote and guide neovascularization during wound healing in mice.
doi_str_mv 10.1002/adhm.201500936
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subjects Animals
Barriers
Bioengineering
Construction
Construction engineering
Cosmetics industry
Drug delivery
Drug delivery systems
Endothelial cells
Endothelial Cells - cytology
Endothelial Cells - metabolism
Endothelial Cells - transplantation
engineered skin
Epidermis
Equivalence
Heterografts
Humans
Immunodeficiency
In vitro testing
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Induced Pluripotent Stem Cells - transplantation
iPSC
Male
Mice
Mice, SCID
microfluidics
Micropatterning
Neovascularization, Physiologic
Networks
patterning
Pluripotency
Skin
Skin - blood supply
Skin - injuries
Skin - metabolism
Stem cells
Three dimensional printing
Vascularization
vasculature
Wound Healing
title Human Skin Constructs with Spatially Controlled Vasculature Using Primary and iPSC-Derived Endothelial Cells
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