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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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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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.</description><identifier>ISSN: 2192-2640</identifier><identifier>EISSN: 2192-2659</identifier><identifier>DOI: 10.1002/adhm.201500936</identifier><identifier>PMID: 27333469</identifier><language>eng</language><publisher>Germany: Blackwell Publishing Ltd</publisher><subject>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</subject><ispartof>Advanced healthcare materials, 2016-07, Vol.5 (14), p.1800-1807</ispartof><rights>2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Copyright © 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c7076-de6118690400d64ff0306faf68460014cc068b2bc360d22c2fd037057d09b5f43</citedby><cites>FETCH-LOGICAL-c7076-de6118690400d64ff0306faf68460014cc068b2bc360d22c2fd037057d09b5f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fadhm.201500936$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fadhm.201500936$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27333469$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abaci, Hasan E.</creatorcontrib><creatorcontrib>Guo, Zongyou</creatorcontrib><creatorcontrib>Coffman, Abigail</creatorcontrib><creatorcontrib>Gillette, Brian</creatorcontrib><creatorcontrib>Lee, Wen-han</creatorcontrib><creatorcontrib>Sia, Samuel K.</creatorcontrib><creatorcontrib>Christiano, Angela M.</creatorcontrib><title>Human Skin Constructs with Spatially Controlled Vasculature Using Primary and iPSC-Derived Endothelial Cells</title><title>Advanced healthcare materials</title><addtitle>Adv. Healthcare Mater</addtitle><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.</description><subject>Animals</subject><subject>Barriers</subject><subject>Bioengineering</subject><subject>Construction</subject><subject>Construction engineering</subject><subject>Cosmetics industry</subject><subject>Drug delivery</subject><subject>Drug delivery systems</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelial Cells - transplantation</subject><subject>engineered skin</subject><subject>Epidermis</subject><subject>Equivalence</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Immunodeficiency</subject><subject>In vitro testing</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Induced Pluripotent Stem Cells - transplantation</subject><subject>iPSC</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>microfluidics</subject><subject>Micropatterning</subject><subject>Neovascularization, Physiologic</subject><subject>Networks</subject><subject>patterning</subject><subject>Pluripotency</subject><subject>Skin</subject><subject>Skin - blood supply</subject><subject>Skin - injuries</subject><subject>Skin - metabolism</subject><subject>Stem cells</subject><subject>Three dimensional printing</subject><subject>Vascularization</subject><subject>vasculature</subject><subject>Wound Healing</subject><issn>2192-2640</issn><issn>2192-2659</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkkFP3DAQhaOqqCDg2mMVqZdesh3b8SS5VEKBZStBi7TQHi1v7LAGJ9naCXT_fb0KjWgPLb7Y0nzzNPP8ougtgRkBoB-lWjczCoQDFAxfRQeUFDShyIvX0zuF_ejY-zsIBznBnLyJ9mnGGEuxOIjsYmhkGy_vTRuXXet7N1S9jx9Nv46XG9kbae12V-ldZ61W8Tfpq8HKfnA6vvGmvY2vnGmk28ayVbG5WpbJqXbmIaBnrer6tbZBIy61tf4o2qul9fr46T6MbuZn1-Uiufh6_rk8uUiqDDJMlEZCciwgBVCY1jUwwFrWmKcIQNKqAsxXdFUxBEVpRWsFLAOeKShWvE7ZYfRp1N0Mq0arSofppRWbcVDRSSP-rLRmLW67B8GBEchJEPjwJOC6H4P2vWiMr8IKstXd4AXJGedYZGnxAjTsUuSU4gtQQMgyzCGg7_9C77rBtcE0sfteZIQz_BcVtHjK85TlgZqNVOU6752uJyMIiF2OxC5HYspRaHj33L4J_52aABQj8Gis3v5HTpycLi6fiydjr_G9_jn1SncvMGMZF9-_nAs2p3h5PV8Kxn4BkRPhfg</recordid><startdate>201607</startdate><enddate>201607</enddate><creator>Abaci, Hasan E.</creator><creator>Guo, Zongyou</creator><creator>Coffman, Abigail</creator><creator>Gillette, Brian</creator><creator>Lee, Wen-han</creator><creator>Sia, Samuel K.</creator><creator>Christiano, Angela M.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QP</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T5</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7TO</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope><scope>7QO</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>201607</creationdate><title>Human Skin Constructs with Spatially Controlled Vasculature Using Primary and iPSC-Derived Endothelial Cells</title><author>Abaci, Hasan E. ; 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Healthcare Mater</addtitle><date>2016-07</date><risdate>2016</risdate><volume>5</volume><issue>14</issue><spage>1800</spage><epage>1807</epage><pages>1800-1807</pages><issn>2192-2640</issn><eissn>2192-2659</eissn><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.
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.</abstract><cop>Germany</cop><pub>Blackwell Publishing Ltd</pub><pmid>27333469</pmid><doi>10.1002/adhm.201500936</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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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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