Novel technologies for engineering closure of non-healing skin wounds

在正常人中，大多数皮肤伤口在几天内就会愈合。然而，在患有糖尿病或血管问题的患者中，皮肤伤口可能会保持开放，导致**“慢性”或无法愈合的伤口的形成。这种伤口通常会给患者带来巨大的心理和身体上的痛苦，并经常导致截肢甚至死亡。**尽管进行了广泛的研究，但对于无法愈合的皮肤伤口，可重复的治疗方法仍然**难以实现。皮肤由许多不同的蛋白质组成，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**的蛋白质在伤口处产生，形成细胞附着并继续移动的支架。**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，但在受伤后表达上调。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，伤口内没有形成支架，这意味着伤口**无法修复。Periostin和CCN2在抑制炎症和诱导下一阶段修复方面非常重要，在修复过程中，细胞进入伤口并生成新组织。我们制作了由Periostin和CCN2纤维组成的支架，并证明了它们能使**细胞进入糖尿病小鼠的伤口并关闭伤口。此外，它们还有助于将血管吸引到伤口中。我们现在已经组成了一个由生物学家、工程师、成像专家、兽医、临床医生和**工业合作者Advanced BioMatrix组成的多学科协作研究**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，这是在**人类身上测试支架之前所需的。如果成功，这项提议将导致新材料的开发，这些材料可以**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.