A therapy for improving diabetic ulcer healing

糖尿病溃疡是糖尿病的主要并发症之一，其主要原因是治疗不当。 高血糖症。糖尿病患者中糖尿病溃疡的患病率从14%到24%不等。在美国， 糖尿病溃疡每年影响90多万人，每年导致80,000例截肢。确实是 据估计，糖尿病溃疡的治疗占#年治疗总费用的三分之一以上。 发达国家的糖尿病并发症。目前糖尿病溃疡的治疗主要集中在 消除感染，使用敷料保持伤口床湿润，卸载高压。 四肢，以及清创以促进愈合。尽管这些措施改善了 患者中，缺乏能够显著改善慢性伤口愈合的药物治疗 糖尿病患者。显然，可以促进伤口愈合和防止复发的新疗法 糖尿病中的慢性溃疡是非常需要的。最近的研究表明，肾上腺髓质素家族多肽 在调节血管生成和免疫反应方面发挥关键作用，并可以预防糖尿病- 相关病因学。这些多肽也被证明可以加速伤口愈合，可能是通过改善 伤口部位的血管生成、免疫反应、血管通透性和组织再生。因为 这些多肽在体内的稳定性较差，是较差的候选药物。为了克服这一障碍，我们有 开发了一系列超激动型类似物，它们可以在原位自组装形成凝胶，并缓慢释放 体内单体类似物。基于这一发现，我们建议开发一种类似的凝胶疗法来治疗 通过改善再上皮化、肉芽形成、血流和促进糖尿病患者创面愈合 伤口环境内的血运重建。在拟议的研究中，我们将(1)确定一种最佳凝胶 在体内提供持续和局部治疗的制剂，以及(2)研究 精选模拟凝胶对两种糖尿病大鼠溃疡模型创面愈合的影响。这项技术的成功开发 新的激素疗法有可能显著降低因以下原因引起的死亡率和发病率 糖尿病患者中无法愈合的足部溃疡。

Diabetic ulcer is one of the major complications of diabetes mellitus because of poor management of hyperglycemia. The prevalence of diabetic ulcer ranges from 14 to 24% among diabetes patients. In the U.S., diabetic ulcer affects over 900,000 peoples a year, and leads to >80,000 limb amputations annually. It was estimated that the management of diabetic ulcers represents over one third of the total cost of treatment of diabetes complications in developed countries. Current management of diabetic ulcers mainly focuses on the elimination of infection, the use of dressings to maintain a moist wound bed, offloading high pressure in the extremities, and debridement to improve healing. Although these measures have improved the survival of patients, there is a lack of pharmacotherapy that can substantially improve the healing of chronic wounds in diabetes patients. Clearly, novel therapeutics that can improve wound healing and prevent the recurrence of chronic ulcers in diabetes are much needed. Recent advance has shown that adrenomedullin family peptides play crucial roles in the regulation of vasculogenesis and immune response, and can protect against diabetes- associated etiology. These peptides have also been shown to accelerate wound healing, perhaps by improving angiogenesis, immune response, vascular permeability, and tissue regeneration in wound sites. Because these peptides have poor stability in vivo, they are poor drug candidates. To overcome this obstacle, we have developed a series of super-agonistic analogs that self-assemble to form gels in situ and slowly release the monomeric analog in vivo. Based on this discovery, we propose to develop an analog gel therapy for accelerating wound healing in diabetes patients by improving re-epithelialization, granulation, blood flow, and revascularization within the wound environment. In the proposed study, we will (1) identify an optimal gel formulation that provides sustained and localized treatment in vivo and (2) investigate the efficacy of the selected analog gel on wound healing in two rodent diabetic ulcer models. Successful development of this novel hormonal therapy has the potential to significantly reduce the mortality and morbidity resulting from nonhealing foot ulcers among diabetes patients.