Developing a new DFU dressing

开发新型 DFU 敷料

• 批准号: 10478476
• 负责人: Sufan Chien
• 金额: $ 87.6万
• 依托单位: NOVERATECH, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-17 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478476
• 关键词: Amputation; Animal Model; Animals; Becaplermin; Blood Platelets; Clinical; Clinical Trials; Collagen; Communities; Complications of Diabetes Mellitus; Cyclic GMP; Diabetes Mellitus; Diabetic Foot Ulcer; Effectiveness; Erythrocytes; FDA approved; Fibrin; Fibroblasts; Genetic Transcription; Granulation Tissue; Growth; Growth Factor; Hospitalization; Hour; Human; Human Volunteers; Hypertrophic Cicatrix; In Situ; Ischemia; Lipids; Lower Extremity; Medicine; Neuropathy; Normal saline; Operative Surgical Procedures; Outcome; Phase; Play; Preparation; Process; Production; Recording of previous events; Recurrence; Reporting; Sterile coverings; Techniques; Testing; Time; Tissues; Toxic effect; United States; Vesicle; Wound models; commercialization; diabetic; effective therapy; effectiveness testing; healing; innovation; macrophage; phenome; preclinical toxicity; success; tissue regeneration; wound; wound care; wound healing

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.

摘要 糖尿病足溃疡（DFU）是非创伤性下肢损伤的主要原因， 截肢在美国，并负责更多的住院治疗比任何 糖尿病的其他并发症尽管过去开发了数千种敷料 世纪以来，没有一种药物显示出作为DFU治疗的任何特定有效性。目前， 即使是最好的治疗方法也只能达到50%的治愈率。 这种愈合通常是暂时的，有66%的机会复发。 有史以来第一次，我们发现了一种可能改变目前 教条。我们已经开发了一种用于细胞内ATP递送的技术（ATP囊泡或 VitaSol™）。当我们使用VitaSol™进行伤口愈合时，肉芽组织开始 24小时内出现。这个新组织不断生长并填满了伤口腔 几天之内，一个从未见过或报道过的现象， 技术.对照敷料，包括生理盐水、游离Mg-ATP、空脂质 囊泡，和唯一的FDA批准的处方生长因子，Regranex，没有 这样的效果。在长时程中，最终愈合时间明显短于对照组 糖尿病和缺血性伤口初步的机理研究表明， 非常快速的组织再生是非常早期（手术后5小时）的结果， 快速和大量巨噬细胞积聚，原位增殖，M2极化， 在传统的成纤维细胞发挥作用之前很久，直接产生胶原蛋白。这种类型的 愈合完全不同于已知的伤口护理的常规过程 纤维蛋白、血小板和红细胞是血细胞的主要成分。 早期的临时基质，逐渐被肉芽组织取代， 3-6天后进入增殖期。虽然VitaSol™的增长 是非常迅速的，它不显示任何不寻常的增长或增生性疤痕形成 在动物中2年后和在有限的人类志愿者中超过9年后。如果这 可以在人体内复制，这将是医学上的重大突破。 我们的中心假设是，细胞内ATP的传递提供了关键的能量， 非常早的时候，激活各种转录机制，导致非常早的 和快速组织再生，迅速填充伤口腔。 在本提案中，我们将针对IND申请开展临床前毒性研究， 并在长期糖尿病的新动物模型中测试VitaSolTM的有效性， 局部缺血和神经病。 我们的细胞内能量输送产品一直被视为 新颖啊该项目的成果将是临床引入一个高度 用于DFU治疗的有效、廉价且易于使用的新敷料。的潜在 影响非常大。