Infection Fighting Polymer Strengthened Biologic Grafts for Abdominal Wall Repair

摘要 生物美学公司正在开发一种新的脱细胞移植物，用于改进腹壁重建(AWR)。 疝气是一种内脏器官穿过肌肉或组织的开口的情况。 已经就位了。在美国，每年有100多万例疝修补术，与医疗保健相对应 每年的成本为480亿美元。疝修补术是普通外科医生最常见的手术。 腹股沟疝--即下腹壁破裂--是最常见的一种需要 修理。AWR通常用于治疗复发或严重的腹股沟疝气。观察到的典型挑战 AWR包括疝气复发、感染和创伤，以及修复材料的失败。最近，最新情况- ART真皮替代物由脱细胞生物移植物(ABG)组成。ABG被广泛使用 用于伤口修复，包括AWR，但由于感染、坏死和 机械故障。有一个重大的未得到满足的需求，即确定安全治疗的新的、创新的方法 接受AWR治疗的患者。 生物美学公司正在开发一种变革性的加载抗生素、聚合物强化的ABG，它可以提供 在愈合过程中将药物转移到手术部位，并提供最佳的再生支架。我们的方法 和应用程序不同于市场上的竞争产品，应该为 改善了患者的预后。我们的初步数据显示，ABG的机械强度以及 模型分子从ABG中释放超过2周。 在这个第一阶段的方案中，将用聚丙交酯-乙交酯(PLGA)聚合物浸渍猪ABG 体内含有抗生素利福平和米诺环素。我们打算(A)展示抗生素在 在体外，(B)评估我们产品的机械性能，以及(C)评估该产品在啮齿动物体内的疗效 AWR模型。如果成功，我们将因此产生概念验证数据，证明我们的抗生素--和 聚合物浸渍的ABGs能够减少感染，促进伤口愈合。

SUMMARY BioAesthetics is developing a novel acellular graft for improved abdominal wall reconstruction (AWR). A hernia is a condition in which an internal organ pushes through an opening in the muscle or tissue that holds it in place. More than one million hernia repair surgeries occur annually in the US, corresponding to healthcare costs of $48 billion annually. Hernia repair is the most common operation performed by general surgeons. Inguinal hernias – in which the lower abdominal wall is breached – are the most common type of hernias requiring repair. AWR is typically performed for treating recurring or severe inguinal hernias. Typical challenges observed with AWR include hernia recurrence, infections and trauma, and repair material failures. Recently, state-of-the- art dermal substitutes have been utilized that consist of acellular biologic grafts (ABGs). ABGs are widely used for wound repair, including AWR, but suffer from complication rates up to 40% due to infection, necrosis, and mechanical failure. There is a significant unmet need to identify novel, innovative approaches to safely treat patients undergoing AWR. BioAesthetics is developing a transformative antibiotic-loaded, polymer-strengthened ABG that delivers drugs to the surgical site during healing and provides an optimal regenerative scaffold. Our approach and application differ from competitive products on the market and should provide superior performance for improved patient outcomes. Our preliminary data demonstrate increased ABG mechanical strength as well as release of a model molecule from the ABG over 2 weeks. In this Phase I proposal, porcine ABGs will be impregnated with poly(lactide-co-glycolide) (PLGA) polymer loaded with the antibiotics rifampin and minocycline. We intend to (a) demonstrate release of the antibiotics in vitro, (b) evaluate mechanical properties of our product, and (c) assess in vivo efficacy of the product in a rodent model of AWR. If successful, we will thus generate proof-of-concept data demonstrating that our antibiotic- and polymer-impregnated ABGs are capable of reducing infection and promoting wound healing.