Smart wound dressing for treating chronic diabetic ulcers

描述(申请人提供)：(糖尿病造成的无法愈合的伤口是这种疾病最常见的并发症之一，导致医疗费用增加、生活质量下降、感染、截肢和死亡。这种疾病的广泛流行及其在不久的将来预计会增加，进一步需要采取旨在促进糖尿病伤口愈合的治疗方法。血管生成和氧合作用是创面愈合过程中的重要参数。在修复组织中，充足的氧气是至关重要的，因为修复过程中对能量的需求增加，如细胞增殖、细菌防御和胶原合成。在正常的急性创面中，新血管生成和血管生成导致组织氧合。然而，在慢性糖尿病创面，血管生成受损；因此，严重缺氧导致愈合能量不足、过度炎症和细菌感染。尽管外源性血管内皮生长因子(VEGF)已被证明可以促进新生血管的生成，但缺氧显著降低了愈合率。我们的假设是，适当的创面氧合结合血管生成因子(如血管内皮生长因子)的传递将促进愈合过程，使免疫细胞能够清除定植的病原体。我们的方法是通过持续监测伤口区域的表皮氧浓度来衡量血管生成，并根据需要在局部释放对愈合过程至关重要的血管内皮生长因子和氧气，从而制作一种智能伤口敷料。为了提高治疗的有效性和测量的准确性，我们建议使用已经被证明更有效的微针来绕过清创。我们建议通过以下步骤开发这项先进的临床相关技术：1)在柔性衬底上制造血管内皮生长因子洗脱微针；2)设计基于微针的氧传感器以及灵活的氧产生和输送模块及其集成；3)在糖尿病创面模型中评估工程平台的体内功能。该设计不仅可以感知创面环境，而且可以控制血管内皮生长因子的释放，调节组织的氧合。

DESCRIPTION (provided by applicant): ( Non-healing wounds caused by diabetes mellitus account for one of the most common complications of this disease leading to increased healthcare cost, decreased quality of life, infections, amputations, and death. The wide prevalence of this disease and its projected increase in the near future has further necessitated therapeutics aimed at enhancing the healing of diabetic wounds. Vascularization and oxygenation are critical parameters in wound healing process. In healing tissue, sufficient oxygenation is critical because of the increased energy demand for reparative processes such as cell proliferation, bacterial defense and collagen synthesis. In normal acute wounds, neoangiogenesis and vascularization result in tissue oxygenation. However, in chronic diabetic wounds, angiogenesis is impaired; thus, severe hypoxia results in insufficient energy for healing, excessive inflammation, and bacterial infection. Although exogenous vascular endothelial growth factor (VEGF) has shown to improve neoangiogenesis, the lack of oxygen significantly reduces the healing rate. Our hypothesis is that the proper oxygenation of wound combined with the delivery of angiogenic factors such as VEGF will enhance the healing process and enable the immune cells to eradicate colonized pathogens. Our approach is to make a smart wound dressing by continuously monitoring epidermal oxygen concentration in the wound area as a measure of angiogenesis and locally releasing VEGF and oxygen which are essential for the healing process on demand. In addition to improve the effectiveness of the therapy and accuracy of measurements, we proposed to bypass the debridement by using microneedles which have already proven to be more effective. We propose to develop this advanced and clinically relevant technology using the following steps: 1) fabricating VEGF eluting microneedles on a flexible substrate; 2) engineering microneedle-based oxygen sensors as well as flexible oxygen generation and delivery modules and their integration; and 3) evaluate the in vivo functionality of the engineered platform in diabetic wound models. The proposed design not only could sense the wound environment, but also can control release VEGF and modulate the tissue oxygenation.