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闭合。然而，在患有糖尿病或血管问题的患者中，皮肤伤口可能保持开放，导致“慢性”或不愈合伤口的发展。这种伤口通常会给患者造成巨大的心理和身体痛苦，并经常导致截肢甚至死亡。尽管进行了广泛的研究，但对于不愈合的皮肤伤口的可重复治疗仍然难以实现。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，但另一种称为基质细胞蛋白的蛋白质在伤口床中产生，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。这些蛋白质通常不存在，但在损伤后上调。然而，我们对慢性伤口的分析发现，这些基质细胞蛋白中的两种，骨膜蛋白和结缔组织生长因子（CCN 2）缺失，并且在伤口中没有形成支架，这意味着它无法修复。骨膜蛋白和CCN 2在关闭炎症和诱导下一阶段的修复中非常重要，在下一阶段，细胞进入伤口并形成新组织。我们制作了由骨膜蛋白和CCN 2纤维组成的支架，并证明它们能使细胞进入糖尿病小鼠的伤口并使其闭合。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多学科的合作研究团队，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，以优化制造协议，并将我们的工作转移到一个大型动物模型中，这将是在人体内测试支架之前所需的。如果成功的话，这项提议将导致新材料的开发，可用于使慢性皮肤伤口愈合。

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.