Infection Fighting Polymer Strengthened Biologic Grafts for Abdominal Wall Repair

用于腹壁修复的抗感染聚合物强化生物移植物

• 批准号: 10546671
• 负责人: Nicholas Pashos
• 金额: $ 25.87万
• 依托单位: BIOAESTHETICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546671
• 关键词: Abdominal Muscles; Address; Anisotropy; Anti-Infective Agents; Antibiotics; Biological; Biological Assay; Categories; Cell Survival; Cells; Characteristics; Clinical; Collagen; Complex; Complication; Data; Deposition; Dermal; Diffusion; Drug Delivery Systems; Elastin; Extracellular Matrix; Failure; Family suidae; Generations; Glycolates; Glycolic-Lactic Acid Polyester; Goals; Health Care Costs; Hernia; Histologic; Human; Hydrogels; Immune; In Vitro; Infection; Infiltration; Inguinal Hernia; Lactic acid; Measures; Mechanics; Medical; Minocycline; Modeling; Modulus; Muscle; Muscle Cells; Muscle Fibers; Necrosis; Operative Surgical Procedures; Organ; Outcome; Patient-Focused Outcomes; Patients; Penetration; Performance; Pharmaceutical Preparations; Phase; Polymers; Postoperative Period; Preclinical Testing; Predisposition; Rattus; Reconstructive Surgical Procedures; Recurrence; Repair Material; Rifampin; Rodent; Rodent Model; Site; Skin; Sprague-Dawley Rats; Staphylococcal Infections; Staphylococcus epidermidis; Surgeon; Surgical Mesh; Surgical Wound Infection; System; Techniques; Testing; Time; Tissues; Trauma; Treatment Efficacy; Vascularization; Work; abdominal wall; biomaterial compatibility; cohort; cytotoxicity; drug release kinetics; efficacious treatment; falls; fighting; healing; implantation; improved; in vivo; in vivo evaluation; innovation; mechanical properties; minimal risk; novel; operation; pathogen; reconstruction; regenerative; repaired; scaffold; systems research; wound; wound healing

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.

概括 BioAesthetics 正在开发一种新型脱细胞移植物，用于改善腹壁重建 (AWR)。 疝气是一种内脏器官穿过肌肉或组织中的开口的情况。 美国每年进行超过一百万例疝气修复手术，与医疗保健相对应。 疝修补术是普通外科医生最常见的手术，每年花费 480 亿美元。 腹股沟疝气（下腹壁破裂）是最常见的疝气类型，需要 AWR 通常用于治疗复发性或严重的腹股沟疝气。 与 AWR 相关的问题包括疝气复发、感染和创伤以及修复材料失效。 已广泛使用由无细胞生物移植物（ABG）组成的真皮替代品。 用于伤口修复，包括 AWR，但由于感染、坏死和感染等原因，并发症发生率高达 40% 寻找新颖、创新的安全治疗方法的需求尚未得到满足。 接受 AWR 的患者。 BioAesthetics 正在开发一种变革性的负载抗生素、聚合物强化的 ABG，可提供 我们在最佳治疗药物期间对手术部位进行治疗并提供再生支架。 和应用程序与市场上的竞争产品不同，应提供卓越的性能 我们的初步数据表明 ABG 机械强度和患者治疗效果均得到改善。 两周内从 ABG 中释放模型分子。 在此第一阶段提案中，猪 ABG 将用聚丙交酯乙交酯 (PLGA) 聚合物浸渍 载有抗生素利福平和米诺环素，我们打算 (a) 证明抗生素的释放。 体外，(b) 评估我们产品的机械性能，以及 (c) 评估产品在啮齿动物体内的功效 如果成功，我们将生成概念验证数据，证明我们的抗生素和 聚合物浸渍的 ABG 能够减少感染并促进伤口愈合。