Parameters for re-engineering stump skin to alleviate pressure ulcers

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Pressures ulcers, also known as bedsores or decubitus ulcers, are a severely debilitating condition that affect half a million people per year in the UK. Pressure ulcers arise when the skin and muscle is compressed between a bony prominence and a hard surface, eg the sitz bone on the buttocks and a wheel chair, or the tibia of an amputated stump and a prosthetic device. In response to compression the soft tissue is deformed, blood capillaries are cut-off and the tissue becomes starved of oxygen and nutrients resulting in cell death. Muscle has a lower tolerance to internal pressures than skin, and ulceration therefore often starts within the interior muscle before effects are observed on the skin surface. Current strategies to alleviate pressure ulcer formation involve modification of the external environment to reduce compression and shear forces on the skin. In this research proposal, we aim to characterise whether, and by how much, modification of the skin itself would alleviate pressure ulcer formation. If skin was thicker and stronger could it dissipate compressive and shear forces, so they do not reach the muscle and cause deformation, cell death and ulceration? We plan to re-engineer stump skin so it acquires the material and behavioural properties of plantar skin. Plantar skin is thicker, more compliant, and has a lower frictional coefficient than skin on other body sites. We believe these properties will help in dissipation of compressive and shear forces. This entire proposal utilises human cells isolated from leg and foot skin biopsies to engineer skin constructs in a lab that represent different sites on the body (leg and plantar). In work plan 1 of this proposal we will sequence constructs representing leg skin, plantar skin, and re-engineered leg skin to determine the molecular properties of the different skin types. In work plan 2 we will assess whether skin from different body sites adapts differently to mechanical compression. We hypothesise that plantar skin, and re-engineered leg skin will have a molecular signature that enables adaptation and an increase in skin thickness in response to compression. Comparatively, we believe that leg skin constructs will break down in response to pressure, indicative of blister formation. We will link the molecular properties of skin with the ability to adapt and increase in thickness in response to mechanical compression. In work plan 3 we will determine the material properties of skin constructs representing different body sites. We will then integrate this into mathematical models in work plan 4 to evaluate if changing the material properties of skin on an amputated stump will dissipate compressive and shear forces, lowering internal pressure and stress within the muscle. We will correlate the magnitude of stresses and strains within the muscle with the incidence of pressure ulcers. In summary, we will characterise the molecular and material properties of human skin from different body sites, in addition to assessing the effect of skin re-engineering on properties like adaptation and dissipation. Our overall goal is to determine whether re-engineering stump skin to become like plantar skin is a feasible therapeutic strategy for alleviating pressure ulcers.