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Title: Strategies to optimise angiogenesis in synthetic dermal equivalents using in-vitro models
Author: Potter, M. J.
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
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Large burns necessitate skin cover. Skin grafts provide a simple solution but are limited in availability. Cultured keratinocytes provide epidermal cover but invariably fail unless grafted on dermis. Synthetic Dermal Equivalents (SDEs) are mostly collagen based and are dogged by poor take. This thesis concentrates on enhancing the angiogenic capability of SDEs to increase take. Aims To develop components for a "smart" pro-angiogenic matrix for reliable take. To explore and investigate clinical adjuncts, to increase graft angiogenesis. To evaluate angiogenic factors and extracellular matrix components for endothelial cell migration promotion to include in a potential skin equivalent. To explore the in-vitro angiogenic properties of SDEs and the role/effective regimes of Ultrasound and Topical Negative Pressure (TNP). Greatest growth factor stimulation was from TGFB. Influence of migration by angiogenic factors was minimal compared to fibrin. Basal invasion into collagen was low. Fibrin stimulated migration seven fold over that of collagen (pO.OT ANOVA). Fibrin subunits had equal effect to fibrin. Glycosaminoglycans, Fibronectin and Vitronectin addition increased migration over that of collagen. The addition of collagen to fibrin inhibited invasion. Ultrasound at an optimum energy of 0.8W/cm gave a 3 fold increase in migration over control conditions. This was equal to the addition of fibrin. Angiogenesis induced by TNP was optimum in Integra using an intermittent regime. This thesis has shown that collagen, the principal component of all SDEs fails to provide an optimal matrix for invasion of endothelial cells. We have found that the most favourable matrix constituents for endothelial cell migration are fibrin and fibrinogen with fibrin exerting a sevenfold increase in endothelial cell migration over collagen. It has also shown that TNP provides equal endothelial cell ingress to both US and fibrin, only when used intermittently with Integra.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available