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 withdiabetes or vascular problems skin wounds can stay open leading to development of a"chronic" or non-healing wound. Such wounds commonly cause tremendous psychologicaland physical suffering for the patient, and often result in limb amputation and even death.Despite extensive research, reproducible treatments for non-healing dermal wounds remainelusive. 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 matricellularproteins 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. Theseproteins are not normally present, but are upregulated after injury. However, our analysis ofchronic wounds has found that two of these matricellular proteins, periostin and connectivetissue growth factor (CCN2) are missing and no scaffold is formed in the wound, meaning it isunable to repair. Periostin and CCN2 are very important in shutting down inflammation andinducing the next phase of repair, where cells move into the wound and make new tissue. Wemade scaffolds composed of fibres of periostin and CCN2 and demonstrated that they causedcells to enter the wound and close it in diabetic mice. Furthermore, they helped attract bloodvessels into the wounds. We have now formed a multi-disciplinary collaborative researchteam consisting of biologists, engineers, imaging specialists, a veterinarian, clinicians andindustrial collaborators Advanced BioMatrix, to optimize maufacturing protocols and move ourwork into a large animal model that would be required prior to testing of the scaffolds inhumans. If successful, this proposal will lead to the development of new materials that couldbe used to make chronic skin wounds close.