REDUCING LAPAROTOMY WOUND FAILURE

描述（由申请人提供）：本I期提案的具体目的是测试我们新开发的用于腹部伤口裂开的细胞内ATP递送技术。在美国，每年有超过20万例切口疝修补手术，在不考虑生产力损失的情况下，其经济成本接近25亿美元。再手术风险大，复发率高。尽管在外科和手术技术领域取得了许多进步，腹壁切口后疝的形成仍然是一个令人困惑和普遍的问题。尽管预防的重要性显而易见，但很少重视预防，而且50年来发病率没有改变。切口疝的形成是多因素的，但确切的机制尚不清楚。内因和外因造成的伤口分离和细菌感染是造成伤口分离的两个主要因素。这两个因素可能形成恶性循环，导致最终的崩溃。如果采取措施纠正一些导致疝的因素，可能会减少或防止疝的形成——及时一针可以节省九针。Noveratech开发了一种将Mg-ATP直接递送到细胞质（atp囊泡或VitaSolTM）的新技术。这项技术已经在老鼠和兔子的全层切除皮肤伤口上进行了测试。VitaSolTM比所有对照敷料更快地愈合伤口，对照敷料包括单独的Mg-ATP，单独的脂质囊泡，中性霜和唯一fda批准的伤口护理处方生长因子-Regranex。它在24小时内产生肉芽组织。在皮肤切口伤口中，VitaSolTM生产的伤口组织具有更高的拉伸强度、断裂强度和应力/应变比。最惊人的发现是极早的干细胞和巨噬细胞积累伴随着大量胶原蛋白的产生——这种现象在过去的任何其他治疗方式中从未见过或报道过。虽然机制研究不是当前提议的目的，但该技术至少通过三种途径运作：1)嘌呤能受体激活引起的大量干细胞/祖细胞运输和白细胞趋化；2)通过细胞内传递能量改善细胞存活和功能，这对中性粒细胞、淋巴细胞和巨噬细胞发挥其杀菌功能尤为重要；3)活化的巨噬细胞促进胶原生成，减少组织分离、渗出和感染。在这个I期研究中，我们计划扩展我们的初步研究结果，比较VitaSolTM及其单个成分在切口伤口中的作用，并测试其对腹部筋膜愈合的影响，以防止疝。这个项目将

DESCRIPTION (provided by applicant): The specific aim of this phase I proposal is to test our newly developed intracellular ATP delivery technique for abdominal wound dehiscence. More than 200,000 incisional hernia repairs are performed annually in the United States at a financial cost of nearly 2.5 billion dollars without considering the loss of productivity. Reoperation is risky with a higher recurrence rate. Despite many advances in the field of surgery and surgical technique, the formation of hernias following abdominal wall incisions continues to be a perplexing and prevalent problem. Very little emphasis has been placed on prevention despite its obvious importance and the incidence has not been changed over 50 years. The formations of incisional hernias are multifactorial, but the exact mechanism is still unknown. Two major contributing factors are wound separation due to intrinsic and extrinsic factors and bacterial infection. These two factors may form a vicious cycle causing a final breakdown. If measures are taken to correct some of the contributing factors, hernia formation may be reduced or prevented-a stitch in time saves nine. Noveratech has developed a new technique for the delivery of Mg-ATP directly to the cytosol (ATP-vesicles or VitaSolTM). The technique has been tested in full-thickness excisional skin wounds in mice and rabbits. VitaSolTM healed wounds faster than all control dressings, which included Mg-ATP alone, lipid vesicles alone, a neutral cream, and the only FDA-approved prescription growth factor for wound care--Regranex. It generated granulation tissues within 24 hours. In incisional skin wounds, VitaSolTM produced wound tissues with much higher tensile strengths, breaking strengths, and stress/strain ratios. The most striking finding was an extremely early stem cell and macrophage accumulation accompanied by massive collagen production-a phenomenon never seen or reported in the past with any other treatment modalities. Although mechanistic study is not the aim of the current proposal, this technique operates via at least three pathways: 1) massive stem/progenitor cell trafficking and leukocyte chemotaxis caused by purinergic receptor activation; 2) improved cell survival and function by intracellularly delivered energy, which is especially important for neutrophils, lymphocytes, and macrophages to exert their bacteriocidal function; and 3) enhanced collagen production by activated macrophages resulting in reduced tissue separation, exudation, and infection. In this phase I study, we plan to expand our preliminary findings to compare VitaSolTM with its individual components in incisional wounds and to test its effects on abdominal fascial healing to prevent herniation. The project will fill a major gap in current surgical wound management. Noveratech plans to commercialize the product after proven effective in animal and human tests. The success of this product will benefit millions of patients who undergo abdominal surgery each year. The usage of this technique may be expanded to other surgical repair procedures and acute wounds. The potential impact is high.