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.

总结 BioAesthetics正在开发一种新型的脱细胞移植物，用于改善腹壁重建（AWR）。 疝气是一种情况，其中内部器官通过肌肉或组织中的开口推动， 它在地方。在美国，每年有超过100万例疝修补手术， 每年花费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-其中下腹壁破裂-是最常见的疝类型， 修复. AWR通常用于治疗复发或严重的腹股沟疝。观察到的典型挑战 AWR包括疝复发、感染和创伤以及修复材料失效。最近，国家- 已经使用了由无细胞生物移植物（ABG）组成的真皮替代物。ABG被广泛使用 用于伤口修复，包括AWR，但由于感染、坏死和 机械故障有一个显著的未满足的需求，以确定新的，创新的方法，以安全地治疗 接受AWR的患者。 BioAesthetics正在开发一种变革性的载药、聚合物强化ABG， 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 和应用不同于市场上的竞争产品，应提供上级性能， 改善患者结局。我们的初步数据表明，ABG机械强度增加， 在2周内从ABG释放模型分子。 在本I期提案中，猪ABG将用聚（丙交酯-共-乙交酯）（PLGA）聚合物浸渍 装满了抗生素利福平和米诺环素我们打算（a）证明抗生素在 体外，（B）评价我们产品的机械性能，和（c）评估产品在啮齿动物中的体内功效 AWR模型如果成功，我们将产生概念验证数据，证明我们的抗生素- 聚合物浸渍的ABG能够减少感染并促进伤口愈合。