Novel technologies for engineering closure of non-healing skin wounds

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In normal individuals, most skin wounds close within a few days. However, in patients with**diabetes or vascular problems skin wounds can stay open leading to development of a**"chronic" or non-healing wound. Such wounds commonly cause tremendous psychological**and physical suffering for the patient, and often result in limb amputation and even death.**Despite extensive research, reproducible treatments for non-healing dermal wounds remain**elusive. Skin is composed of many different protein types, which change when skin is injured.**Proteins such as collagen provide structural support, but another type known as matricellular**proteins are produced in the wound bed and form a scaffold that cells attach to and move on.**However, these proteins provide cells the instructions on how to repair the tissue. These**proteins are not normally present, but are upregulated after injury. However, our analysis of**chronic wounds has found that two of these matricellular proteins, periostin and connective**tissue growth factor (CCN2) are missing and no scaffold is formed in the wound, meaning it is**unable to repair. Periostin and CCN2 are very important in shutting down inflammation and**inducing the next phase of repair, where cells move into the wound and make new tissue. We**made scaffolds composed of fibres of periostin and CCN2 and demonstrated that they caused**cells to enter the wound and close it in diabetic mice. Furthermore, they helped attract blood**vessels into the wounds. We have now formed a multi-disciplinary collaborative research**team consisting of biologists, engineers, imaging specialists, a veterinarian, clinicians and**industrial collaborators Advanced BioMatrix, to optimize maufacturing protocols and move our**work into a large animal model that would be required prior to testing of the scaffolds in**humans. If successful, this proposal will lead to the development of new materials that could**be used to make chronic skin wounds close.