Novel technologies for engineering closure of non-healing skin wounds

对于正常人来说，大多数皮肤伤口会在几天内愈合。然而，对于患有糖尿病或血管问题的患者，皮肤伤口可能保持开放，导致“慢性”或不愈合伤口的发展。这种伤口通常会给病人造成巨大的心理和身体上的痛苦，往往会导致截肢甚至死亡。尽管进行了广泛的研究，但对于无法愈合的皮肤伤口的可重复性治疗仍然难以捉摸。皮肤由许多不同类型的蛋白质组成，当皮肤受伤时，这些蛋白质会发生变化。胶原蛋白等蛋白质提供结构支持，但另一种被称为基质细胞蛋白的蛋白质在伤口床上产生，形成细胞附着和移动的支架。然而，这些蛋白质为细胞提供了如何修复组织的指令。这些蛋白通常不存在，但在损伤后上调。然而，我们对慢性伤口的分析发现，其中两种基质细胞蛋白，骨膜蛋白和结缔组织生长因子（CCN2）缺失，伤口中没有形成支架，这意味着它无法修复。骨膜蛋白和CCN2对于关闭炎症和诱导下一阶段的修复非常重要，在修复阶段，细胞进入伤口并形成新的组织。我们制作了由骨膜蛋白纤维和CCN2组成的支架，并证明它们可以使细胞进入糖尿病小鼠的伤口并关闭伤口。此外，它们有助于吸引血管进入伤口。我们现在已经组建了一个由生物学家、工程师、成像专家、兽医、临床医生和工业合作者组成的多学科合作研究团队Advanced biommatrix，以优化制造方案，并将我们的工作转移到大型动物模型中，这将是在人体支架测试之前需要的。如果成功，这一提议将导致新材料的发展，可用于闭合慢性皮肤伤口。

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.