Developing a new DFU dressing

摘要 糖尿病足溃疡(DFU)是导致非创伤性下肢的主要原因。 在美国截肢，住院人数比以往任何时候都多 糖尿病的其他并发症。尽管过去开发了数以千计的调料 一个世纪以来，没有一种疗法像DFU治疗那样显示出任何特定的疗效。目前， 即使是最好的治疗方法也只能达到50%的治愈率。 伤口--这种愈合通常是暂时的，有66%的复发率。 历史上第一次，我们找到了一种可能改变当前情况的方法 教条。我们已经开发出一种细胞内ATP递送技术(ATP-囊泡或 VitaSol™)。当我们使用VitaSol™进行伤口愈合时，肉芽组织开始 在24小时内出现。这种新组织不断生长，填满伤口的空洞。 在几天内，一种以前从未见过或报道过的现象 技巧。对照敷料，包括生理盐水、游离镁-三磷酸腺苷、空脂 囊泡，以及FDA批准的唯一处方生长因子Regranex，没有 这样的影响。最终愈合时间明显短于对照组。 糖尿病合并缺血性伤口。一项初步的机制研究表明， 极快的组织再生是非常早的(手术后5小时)的结果， 巨噬细胞快速大量聚集，原位增殖，M2极化，以及 直接产生胶原蛋白，早在传统的成纤维细胞开始发挥作用之前。这种类型的 愈合过程完全不同于传统的伤口护理过程 社区，在那里，纤维蛋白、血小板和红细胞是 早期临时基质，在移植过程中逐渐被肉芽组织取代 增殖期后3-6天滞留时间。尽管VITASOL™的增长 非常迅速，没有任何异常生长或增生性疤痕形成 经过2年的动物实验和9年多的有限人类志愿者实验。如果这个 可以在人类身上复制，这将是医学上的重大突破。 我们的中心假设是，细胞内的ATP传递在 非常早的时候，激活各种转录机制，导致极早的 以及快速的组织再生，迅速填满伤口腔。 在这项提案中，我们将进行一项针对IND应用的临床前毒性研究， 并在一种新的长期糖尿病动物模型上测试VitaSolTM的有效性， 脑缺血和神经病变。 我们的细胞内能量传递产品一直被视为 创新。该项目的成果将是临床上引入一种高度 治疗DFU的有效、廉价、易用的新敷料。潜力 影响非常大。

ABSTRACT Diabetic foot ulcers (DFUs) are the leading cause of nontraumatic lower extremity amputations in the United States and are responsible for more hospitalizations than any other complication of diabetes. Despite thousands of dressings developed in the past century, none have shown any specific effectiveness as DFU treatments. Currently, even the best available treatments achieve only a 50% healing rate for these wounds—and this healing is often temporary, with a 66% chance of recurrence. For the first time in history, we have found an approach that may change the current dogma. We have developed a technique for intracellular ATP delivery (ATP-vesicles or VitaSol™). When we use VitaSol™ for wound healing, granulation tissue starts to appear within 24 hours. This new tissue keeps growing and fills the wound cavity within a few days, a phenomenon never seen or reported before by any other techniques. Control dressings, including normal saline, free Mg-ATP, empty lipid vesicles, and the only FDA-approved prescription growth factor, Regranex, have no such effects. The final healing time is much shorter than the controls in long-time diabetic plus ischemic wounds. A preliminary mechanistic study has shown that the extremely rapid tissue regeneration is the result of very early (5 hours after surgery), rapid, and massive macrophage accumulation, in situ proliferation, M2 polarization, and direct collagen production, long before traditional fibroblasts come into play. This type of healing is totally different from the conventional process known to the wound care community, where fibrin, platelets, and red blood cells are the main components of the early provisional matrix, which is gradually replaced by granulation tissue during the proliferation phase after 3–6 days of lag time. Although the growth seen with VitaSol™ is extremely rapid, it does not display any unusual growth or hypertrophic scar formation after 2 years in animals and after more than 9 years in limited human volunteers. If this can be duplicated in humans, it will be a major breakthrough in medicine. Our central hypothesis is that intracellular ATP delivery provides critical energy at very early time, activates various transcription mechanisms, resulting in extremely early and rapid tissue regeneration that fills the wound cavity quickly. In this proposal, we will perform a preclinical toxicity study aimed at IND application, and test the effectiveness of VitaSolTM in a new animal model with long-term diabetes, ischemia, and neuropathy. Our product for intracellular energy delivery has consistently been viewed as innovative. The outcome of this project will be the clinical introduction of a highly effective, inexpensive, and easy-to-use new dressing for DFU treatment. The potential impact is very high.