Surgical Wound Closure Matrices for the Prevention of Superficial Incisional SSI

第一阶段SBIR提案的目的是测试组织内抗菌手术的可行性 伤口基质预防浅表手术部位皮肤感染。手术部位感染（SSI） 是第二种最常见的卫生保健相关感染（HAI），发生在2%至5%的患者中 在美国接受手术，约占医疗保健死亡人数的2.0%- 相关感染。这些感染导致了370万个额外的住院日， 每年医疗保健支出10亿美元。 目前预防SSI的方法包括术前和围手术期全身使用抗生素， 围手术期应用含抗生素药物（庆大霉素、万古霉素）敷料或珠粒，并严格 遵守手术室无菌技术规程。全身使用抗生素的疗效明显降低 由于半衰期短于2小时，因此需要坚持仔细定时的药物递送。的 局部抗生素的使用受到有限功效的挑战。全身和局部使用抗生素 受到对多药耐药生物体（MDRO）无效的困扰。G4 Surg，申报产品 通过独特的作用机制预防/消除感染，克服了目前的局限性， 广谱抗菌G4 Surg利用电荷组成对革兰氏菌产生毒性， 阳性和阴性细菌（包括抗生素耐药菌株）。此外，G4 Serg仅依赖于 序列的抗微生物电荷比，因此是细胞友好的，非炎性的，无毒的。 为了确定治疗糖尿病伤口的可行性，我们提出了以下两个具体目标： 具体目标1：通过体内安全性研究，证明G4 Surg在切口期间的生物相容性 伤口愈合 具体目标2：通过体内疗效研究，证明G4 Surg清除感染细菌的能力 腹部切口 在SBIR第二阶段，我们将在大型动物模型中验证G4 Surg在感染伤口愈合中的疗效， 更广泛的细菌菌株，包括益生菌和生物膜形式，并为FDA执行GLP研究 成绩.

The goal of this Phase I SBIR proposal is to test the feasibility of an intra-tissue antimicrobial surgical wound matrix in the prevention of superficial surgical site skin infections. Surgical Site Infections (SSI) are the second most common type of health care–associated infection (HAI), occurring in 2% to 5% of patients undergoing surgery in the United States, and accounting for approximately 2.0% of deaths due to health care- associated infections. These infections have resulted in 3.7 million excess hospital days, and close to $10 billion in health care expenditure annually. Current methods for SSI prevention include preoperative and perioperative systemic antibiotic use, perioperative application of antibiotic drug-containing (gentamicin, vancomycin) dressings or beads, and strict adherence to OR sterile technique procedures. The efficacy of systemic antibiotic use is significantly reduced by the requirement to adhere to carefully timed drug delivery due to short half-lives of less than 2 hours. The use of topical antibiotics has been challenged by the limited efficacy. Both systemic and topical antibiotic uses are plagued by inefficacy against multi-drug resistant organisms (MDROs). G4Surg, the proposed product overcomes current limitations by preventing/eliminating infection through a unique mechanism of action that is broad spectrum antibacterial. G4Surg takes advantage of charge composition to exert toxicity against Gram- positive and -negative bacteria (including antibiotic resistant strains). Furthermore, G4Serg relies only on sequences for antimicrobial charge ratio, and therefore is cell friendly, non-inflammatory, and nontoxic. To establish feasibility for the treatment of diabetic wounds, we propose the following two specific aims: Specific Aim 1: Through in vivo safety studies, demonstrate biocompatibility of G4Surg during incisional wound healing. Specific Aim 2: Through in vivo efficacy studies, demonstrate G4Surg's ability to clear bacteria infected abdominal incisional wounds. In SBIR Phase II, we will validate G4Surg efficacy in infected wound healing in a large animal model, test a wider range of bacterial strains in planktonic and biofilm forms, and execute GLP studies for our FDA submission.