The aim of the current project is to investigate a new family of polymers specifically tailored to control the behaviour of the cells responsible for wound repair following burn injuries. We are interested in finding out how alterations in the molecular and nanoscale structure of these materials affects the keratinocyte and fibroblast cells which form the outermost and deeper layers of skin respectively.
It is known that these cells respond to the nanoscale and molecular structure of the substrate on which they grow and become aligned and change their behaviour. By altering the structure of the material surrounding the cells the amount of strain a cell experiences may be controlled, so reducing the expression of the contractile phenotype which leads to scarring.
When cutaneous wounds heal following injuries such as burns, the extracellular matrix plays a pivotal role in modulating the behaviour of the cells responsible for the healing process. During this process dermal fibroblasts are recruited to the site of injury where they proliferate and synthesize extracellular matrix (ECM) components such as collagen and fibronectin.
In response to a number of stimuli including mechanical strain, and growth factors such as transforming growth factor β-1 (TGF-β1), the dermal fibroblasts differentiate towards a contractile, myofibroblast phenotype and express α-smooth muscle actin (αSMA). Synthesis of this contractile protein results in wound contraction, which in a normal healing wound provides an important contribution to wound closure.
In addition, epithelial cells migrate from the wound margins and from any remaining skin appendages, such as sebaceous glands, and proliferate and differentiate to form a renewed stratified epithelium. However, some wounds heal poorly resulting in the formation of abnormal scar tissue, such as the development of hypertrophic or keloid scars.
Over-expression of a myofibroblast phenotype by dermal fibroblasts leads to fibrosis and contraction of the scar tissue to form scar contractures. Scarring can be unsightly and result in functional limitations such as restrictions in joint movement. In full thickness wounds such as severe burns this process can be particularly debilitating.
There is increasing evidence that nanostructured materials can have a significant effect in modulating cell behaviour, particularly with respect to cell fate and differentiation. The use of electrospinning to produce nanofibre scaffolds for cutaneous wound repair allows a large degree of control over the nanoscale structure of the ECM.
The structure of a scaffold can be changed by altering variables such as the thickness of the nanofibres, their density, distribution and chemistry. By optimising these variables, a template can be fabricated with an optimised structure and mechanical properties, into which cells can migrate and proliferate, in order to regenerate damaged cutaneous tissue.
By developing such nanostructured materials optimised towards providing an extracellular environment in which skin cells can regenerate damaged tissue, improvements may be brought about in the treatment of patients suffering from burns and other cutaneous injuries.
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