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Development of Novel Non-Scarring Ti...
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Varkey, Mathew.
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Development of Novel Non-Scarring Tissue Engineered Skin to Treat Burn Patients and Others with Extensive Skin Loss.
Record Type:
Electronic resources : Monograph/item
Title/Author:
Development of Novel Non-Scarring Tissue Engineered Skin to Treat Burn Patients and Others with Extensive Skin Loss./
Author:
Varkey, Mathew.
Description:
227 p.
Notes:
Source: Dissertation Abstracts International, Volume: 75-05(E), Section: B.
Contained By:
Dissertation Abstracts International75-05B(E).
Subject:
Health Sciences, Surgery. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR96414
ISBN:
9780494964149
Development of Novel Non-Scarring Tissue Engineered Skin to Treat Burn Patients and Others with Extensive Skin Loss.
Varkey, Mathew.
Development of Novel Non-Scarring Tissue Engineered Skin to Treat Burn Patients and Others with Extensive Skin Loss.
- 227 p.
Source: Dissertation Abstracts International, Volume: 75-05(E), Section: B.
Thesis (Ph.D.)--University of Alberta (Canada), 2013.
Tissue engineered skin containing autologous fibroblasts and keratinocytes on collagen-glycosaminoglycan (C-GAG) matrices are the preferred skin substitutes for wound repair when loss of skin is extensive as in burns. A significant negative outcome of wound healing is hypertrophic scarring (HTS), a dermalfibroproliferative disorder, that leads to considerable morbidity. Dermal fibroblasts, the cells that mediate wound healing and HTS are heterogeneous; they consist of superficial (SF), deep (DF) and hair follicle fibroblasts. Previous studies have shown that DF maybe responsible for HTS. The goal of this project was therefore to further characterize SF and DF, explore new targets for treatment of HTS and develop tissue engineered skin with anti-scarring properties, for use in patients with extensive skin loss.
ISBN: 9780494964149Subjects--Topical Terms:
1681670
Health Sciences, Surgery.
Development of Novel Non-Scarring Tissue Engineered Skin to Treat Burn Patients and Others with Extensive Skin Loss.
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227 p.
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Source: Dissertation Abstracts International, Volume: 75-05(E), Section: B.
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Adviser: Edward Tredget.
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Thesis (Ph.D.)--University of Alberta (Canada), 2013.
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Tissue engineered skin containing autologous fibroblasts and keratinocytes on collagen-glycosaminoglycan (C-GAG) matrices are the preferred skin substitutes for wound repair when loss of skin is extensive as in burns. A significant negative outcome of wound healing is hypertrophic scarring (HTS), a dermalfibroproliferative disorder, that leads to considerable morbidity. Dermal fibroblasts, the cells that mediate wound healing and HTS are heterogeneous; they consist of superficial (SF), deep (DF) and hair follicle fibroblasts. Previous studies have shown that DF maybe responsible for HTS. The goal of this project was therefore to further characterize SF and DF, explore new targets for treatment of HTS and develop tissue engineered skin with anti-scarring properties, for use in patients with extensive skin loss.
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Biochemical and biomechanical assessment of C-GAG matrices independently seeded with SF or DF revealed differential matrix remodelling. Matrices with DF were more contracted and stiffer and had significantly higher osteopontin, angiotensin-II, peroxisome-proliferator-activated receptor (PPAR)-alpha, and significantly less tumor necrosis factor-alpha, PPAR-beta/delta/, PPAR-gamma, and the proteoglycan, fibromodulin compared to matrices with SF. These targets could potentially be used for treatment of HTS. Further, when SF or DF were independently co-cultured with keratinocytes on matrices, the resulting engineered skin with SF formed a continuous epidermis with increased epidermal barrier function and higher levels of keratin-5 and E-cadherin, compared to that with DF, which had an intermittent epidermis. Also, engineered skin with SF formed better basement membrane with more laminin-5, nidogen, collagen typeVII, and the proteoglycan, perlecan, compared to that with DF. Furthermore, assessment of epidermal effect on matrix remodelling by SF and DF revealed a significant keratinocytes-mediated inhibition of matrix contraction, TGF-beta1 and collagen production, and myofibroblast-differentiation for DF and not for SF. Also, co-culture of keratinocytes resulted in reduced gene expression of pro-fibrotic, CTGF and fibronectin and increased expression of anti-fibrotic, MMP-1, decorin and fibromodulin for DF and not SF. Taken together, the specific use of SF in tissue engineered skin may be more beneficial than heterogeneous dermal fibroblasts to promote adhesion of newly-formed skin and anti-fibrotic wound healing, and promising for use in treatment of extensive skin loss and other basement membrane disorders.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR96414
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