De Novo Hair Morphogenesis in Engineered Skin Substitutes
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University of Cincinnati / OhioLINK
2012
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337954933 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-ucin13379549332021-08-03T06:15:34Z De Novo Hair Morphogenesis in Engineered Skin Substitutes Sriwiriyanont, Penkanok Biomedical Research trichogenesis engineered skin substitutes dermal papilla hair b-catenin sebaceous gland The use of tissue-engineered skin for treating full-thickness skin loss has been clinically proven to efficiently restore skin barrier function and considerably improve the rate of survival in pediatric burn patients. Nonetheless, the ultimate goal to restore native skin structures and appearance remains today’s major challenge. Lack of skin appendages not only impacts the psychological well-being of the patients, but also compromises the inherent functions of skin. Although various hair reconstitution models have been proposed within the past decades, most are depended upon the use of high trichogenic non-cultured fetal or newborn dermal and epidermal cells, which limit their use for hair regeneration in tissue-engineered skin. In this study, the feasibility of de novo hair morphogenesis in engineered skin substitutes by the use of expanded cultured dermal and epidermal cells are demonstrated. Although the critical role of specialized dermal mesenchyme during embryonic hair morphogenesis has been well-documented, its trichogenic activity declines sharply when removed from its native environment. Accordingly, in the first part of this study, methods for isolating and culturing dermal papilla cells were investigated. Subsequently, established dermal papilla cell lines are evaluated for their trichogenic activity in the presence and absence of epithelial cells, and the possibility of incorporating them into our current skin substitute model comprised of keratinocytes and fibroblasts was assessed. Finally, trichogenesis in engineered skin substitutes was investigated in vivo after orthopically grafting these engineered skins, comprised of cultured keratinocytes, dermal papilla cells and/or fibroblasts, onto immunodeficient mice. Apart from assessing the necessity of trichogenic dermal papilla cells in hair morphogenesis, the important role of ¿¿¿¿-catenin in epithelium was also investigated by the use of genetically modified keratinocytes overexpressing inducible N-terminally truncated ¿¿¿¿-catenin. In these experiments, we demonstrate that trichogenic dermal papilla cells, but not ¿¿¿¿-catenin overexpressing epithelial cells, play an indispensible role in trichogenesis in engineered skin substitutes, and that adult murine dermal papilla cells have higher trichogenic activity compared to adult human dermal papilla cells. More importantly, compared to engineered skin substitutes prepared using dissociated newborn murine cells, regenerated hairs in human engineered skin lack sebaceous glands, which may hinder proper hair canal development. Taken together, this study provides a practical method for hair regeneration in tissue engineered skin that could be further developed for future use in skin replacement therapy. 2012-10-26 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337954933 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337954933 unrestricted 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 |
Biomedical Research trichogenesis engineered skin substitutes dermal papilla hair b-catenin sebaceous gland |
| spellingShingle |
Biomedical Research trichogenesis engineered skin substitutes dermal papilla hair b-catenin sebaceous gland Sriwiriyanont, Penkanok De Novo Hair Morphogenesis in Engineered Skin Substitutes |
| author |
Sriwiriyanont, Penkanok |
| author_facet |
Sriwiriyanont, Penkanok |
| author_sort |
Sriwiriyanont, Penkanok |
| title |
De Novo Hair Morphogenesis in Engineered Skin Substitutes |
| title_short |
De Novo Hair Morphogenesis in Engineered Skin Substitutes |
| title_full |
De Novo Hair Morphogenesis in Engineered Skin Substitutes |
| title_fullStr |
De Novo Hair Morphogenesis in Engineered Skin Substitutes |
| title_full_unstemmed |
De Novo Hair Morphogenesis in Engineered Skin Substitutes |
| title_sort |
de novo hair morphogenesis in engineered skin substitutes |
| publisher |
University of Cincinnati / OhioLINK |
| publishDate |
2012 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1337954933 |
| work_keys_str_mv |
AT sriwiriyanontpenkanok denovohairmorphogenesisinengineeredskinsubstitutes |
| _version_ |
1719433629962076160 |