A new technique for diabetic foot ulcers

治疗糖尿病足溃疡的新技术

• 批准号: 8905107
• 负责人: Sufan Chien
• 金额: $ 27.55万
• 依托单位: NOVERATECH, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8905107
• 关键词: Animal Testing; Animals; Area; Becaplermin; Calculi; Caring; Cell Proliferation; Cell Survival; Cell membrane; Cells; Characteristics; Chronic; Clinical; Complication; Country; Development; Diabetic Foot Ulcer; Diabetic wound; Drug Controls; Encapsulated; Energy Supply; FDA approved; Female; Functional disorder; Goals; Granulation Tissue; Growth; Growth Factor; Healed; Hemorrhage; Hemostatic function; Hour; Human; Hypertrophic Cicatrix; Inflammation; Insulin-Dependent Diabetes Mellitus; Ischemia; Lipids; Literature; Medicine; Modeling; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Neuropathy; One-Step dentin bonding system; Oryctolagus cuniculus; Phase; Process; Proliferating; Protein Biosynthesis; Reporting; Skin; Specialist; Sterile coverings; Supporting Cell; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Toxic effect; Toxicity Tests; Trauma; Ulcer; Use of New Techniques; Vascular blood supply; Vesicle; Wound Healing; anxious; cell motility; compare effectiveness; diabetic; diabetic patient; effective therapy; healing; innovation; macrophage; male; non-diabetic; novel; novel diagnostics; pressure; public health relevance; response; success; tissue regeneration; treatment strategy; wound

 DESCRIPTION (provided by applicant): This proposal is submitted in response to the new NIDDK announcement (PA-14- 058) calling for development of new diagnostic, monitoring, and therapeutics technologies for the complications of type 1 diabetes (T1D). An estimated 15-25% of the 25.8 million diabetic patients in this country will develop diabetic foot ulcers (DFU) at some point in their lives. Currently, even the best available treatments achieve only a 50% healing rate for these wounds-and this healing is often only temporary with a high chance of recurring. Although the causes of non-healing chronic wounds are multifactorial, one critical pathophysiology is ischemia-a deficient blood supply. Ischemia may not be the initiating factor for DFU, because most ulcers start from a combination of neuropathy, pressure loading, and/or trauma. However, tissue ischemia is the main cause that hinders healing-wounds do not heal in tissue that does not bleed, whereas they always heal in tissue that bleeds extensively. The most critical consequence of ischemia is a decreased cellular energy supply because energy is required in every aspect of the wound healing process from protein synthesis to cell migration, proliferation, and functioning. Our company has developed a technique to encapsulate Mg-ATP into very small unilamellar lipid vesicles for intracellular delivery (ATP-vesicles or VitaSolTM). When we use this new technique in animal wound models, not only healing is enhanced, but also produces an unprecedented result: Granulation tissue starts to appear in less than 24 hours. It continues to grow and covers the whole wound within 3-5 days. Massive cell accumulation and proliferation occur not only on the wound wall, but also in the wound cavity where no blood supply exists. We have never seen this phenomenon in humans or any other land animals, nor has it been reported in the literature by any other treatment strategy. The effect seems even more pronounced in long-term (12 months or longer) diabetic plus ischemic wounds. Although the granulation tissue growth is rapid, it shows a self-limiting feature, which results in no hypertrophic scar formation or any other overgrowth even after 2 years. Like many other wound care specialists, when we first saw this unprecedented result, we did not believe it because it seemed too good to be true. However, this novel healing response has been confirmed in more than 130 rabbits (over 1040 wounds). In this phase I proposal, we will compare VitaSolTM with Regranex, the only FDA- approved prescription growth factor for wound care, in a diabetic wound model without skin contraction, and perform a preliminary toxicity study. The accomplishment of these two goals will bring the project one step closer to IND application. Our technique of intracellular energy delivery has consistently been viewed as innovative. If successful, it will provide an inexpensive and easy to use dressing for DFU treatment, something not yet achieved despite thousands of dressings developed or proposed. The potential impact is high.

 描述（由申请人提供）：本提案是为了响应新的NIDDK公告（PA-14- 058）而提交的，该公告呼吁开发1型糖尿病（T1 D）并发症的新诊断、监测和治疗技术。据估计，该国2580万糖尿病患者中有15-25%会在一生中的某个时候患上糖尿病足溃疡（DFU）。目前，即使是最好的治疗方法也只能达到50%的愈合率，而且这种愈合往往只是暂时的，复发的机会很大。 虽然慢性伤口不愈合的原因是多方面的，但一个关键的病理生理学是缺血-血液供应不足。缺血可能不是DFU的起始因素，因为大多数溃疡都是由神经病变、压力负荷和/或创伤的组合引起的。然而，组织缺血是阻碍愈合的主要原因-伤口在不出血的组织中不会愈合，而在广泛出血的组织中总是愈合。缺血的最关键后果是细胞能量供应减少，因为从蛋白质合成到细胞迁移、增殖和功能的伤口愈合过程的每个方面都需要能量。 我们公司开发了一种将Mg-ATP封装到非常小的单层脂质囊泡中用于细胞内递送的技术（ATP囊泡或VitaSolTM）。当我们在动物伤口模型中使用这种新技术时，不仅愈合得到了加强，而且还产生了前所未有的结果：肉芽组织在不到24小时内开始出现。它会继续生长，并在3-5天内覆盖整个伤口。大量的细胞聚集和增殖不仅发生在伤口壁上，而且发生在没有血液供应的伤口腔中。我们从未在人类或任何其他陆地动物中看到过这种现象，也没有任何其他治疗策略的文献报道。在长期（12个月或更长时间）糖尿病加缺血性伤口中，这种效果似乎更明显。虽然肉芽组织生长迅速，但它显示出自限性特征，即使在2年后也不会导致增生性瘢痕形成或任何其他过度生长。像许多其他伤口护理专家一样，当我们第一次看到这一前所未有的结果时，我们并不相信，因为它似乎太好了。然而，这种新的愈合反应已在130多只家兔（超过1040处伤口）中得到证实。 在本I期提案中，我们将在无皮肤收缩的糖尿病伤口模型中比较VitaSolTM与唯一FDA批准的伤口护理处方生长因子Regranex，并进行初步毒性研究。这两个目标的实现，将使该项目离IND申请又近了一步。 我们的细胞内能量输送技术一直被视为创新。如果成功，它将为DFU治疗提供一种廉价且易于使用的敷料，尽管开发或提出了数千种敷料，但尚未实现。潜在影响很大。