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，但对于不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，在这个修复阶段，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，并证明它们能使**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Advanced BioMatrix组成的多学科合作研究团队，以优化制造方案，并将我们的工作转移到大型动物模型中，这将是在对人体进行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，可用于愈合慢性皮肤伤口。

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.