Engineering the Dermal-Epidermal Junction

Bibliographic Details
Main Author:	Malara, Megan Marie
Language:	English
Published:	The Ohio State University / OhioLINK 2020
Subjects:	Materials Science
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=osu1576759637104844

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-osu15767596371048442021-08-03T07:13:36Z Engineering the Dermal-Epidermal Junction Malara, Megan Marie Materials Science The gold standard treatment for full-thickness burn wounds is a split-thickness autograft. For large total body surface area (TBSA) burns, sufficient donor tissue may not be available for grafting, resulting in a need for alternate autologous tissue sources. Current autologous alternatives include tissue engineered skin and cultured epithelial autografts (CEAs), both of which provide life-saving, permanent wound closure for large TBSA burns. Additionally, these technologies can heal a wound up to 400 times the donor tissue area while conventional mesh and expansion techniques can expand tissue a maximum of 6-fold. Unfortunately, current engineered epidermal or skin alternatives suffer from extreme fragility, slow basement membrane deposition, and lack including the interdigitation of the dermal-epidermal junction (DEJ). The DEJ is an important site for epidermal-mesenchymal communication and anchorage of the epidermal layer. Engineering the DEJ in cultured skin grafts has been investigated in the field through decellularized allodermis, bioprinting, and photolithography with limited success.Moving towards an autologous cultured graft that mimics the DEJ of native skin, topography was patterned into the surface of dermal constructs using a soft lithography process. Collagen type I gels were cast with square features of various depth, width, and frequency. Collagen fibril orientation was impacted by the presence of features with significant alignment seen at the side wall of features that could impose a downstream immune response. Patterned collagen matrices were also fabricated with encapsulated fibroblasts and cultured <i>in vitro</i>. Over time, gel matrices contracted causing feature frequency to increase and become narrower and shallower.To develop a matrix with stable ridges, an electrospun collagen-based dermal template was fabricated. Ridged topographies were patterned into the dermal template using laser ablation. These micropatterned dermal templates were then combined with CEAs prior to grafting to athymic mice. Pairing CEAs with a dermal template led to more rapid deposition of basement membrane proteins. CEAs grafted in conjunction with ridged templates showed rete ridge formation and led to increased epidermal thickness, proliferation, and stemness compared to templates with a flat DEJ. Laser patterned dermal templates were additionally explored as a method to induce rete ridges in an engineered skin model. Upon grafting to athymic mice, ridged grafts exhibited improved barrier function at earlier time points, increased epidermal proliferation and basement membrane deposition.Laser patterning of dermal templates induces an upregulation of pro-inflammatory cytokines. Using lasered dermal templates in an ES model pushes grafts towards a pro-remodeling phase of wound healing. It is believed that both the physical generation of ridges and the changes to cell behavior contribute to rete ridge formation.Overall, these studies suggest engineering the DEJ with ridged structures improves graft development and function. To move this technology towards clinical translation and improved outcomes, methods to incorporate antimicrobial activity into the dermal template along with factors to speed and enhance vascularization are needed. These improvements to the dermal template would not only would allow for superior functional outcomes but would expand the capabilities of the technology for use with other autologous wound closure strategies, including cell sprays. 2020-09-02 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1576759637104844 http://rave.ohiolink.edu/etdc/view?acc_num=osu1576759637104844 restricted--full text unavailable until 2022-05-13 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Materials Science
spellingShingle	Materials Science Malara, Megan Marie Engineering the Dermal-Epidermal Junction
author	Malara, Megan Marie
author_facet	Malara, Megan Marie
author_sort	Malara, Megan Marie
title	Engineering the Dermal-Epidermal Junction
title_short	Engineering the Dermal-Epidermal Junction
title_full	Engineering the Dermal-Epidermal Junction
title_fullStr	Engineering the Dermal-Epidermal Junction
title_full_unstemmed	Engineering the Dermal-Epidermal Junction
title_sort	engineering the dermal-epidermal junction
publisher	The Ohio State University / OhioLINK
publishDate	2020
url	http://rave.ohiolink.edu/etdc/view?acc_num=osu1576759637104844
work_keys_str_mv	AT malarameganmarie engineeringthedermalepidermaljunction
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Engineering the Dermal-Epidermal Junction

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