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 生物作用正在开发一种新型的细胞移植物，以改善腹壁重建（AWR）。 疝气是一种疾病，内部器官穿过肌肉或组织中的开口 它到位。每年在美国进行超过一百万个疝气修复手术，与医疗保健相对应 每年480亿美元的成本。疝气修复是普通外科医生执行的最常见手术。 腹股沟疝（侵犯了下腹壁）是最常见的疝气类型 维修。 AWR通常用于治疗重复或严重的腹股沟疝。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失败。最近， 已利用Art Dermal替代品，由细胞生物学移植物（ABG）组成。 ABG广泛使用 对于包括AWR在内的伤口修复，但由于感染，坏死和 机械故障。识别新颖，创新的方法可以安全治疗有很大的未满足的需求 接受AWR的患者。 Bioaesthetics正在开发一种变换的抗生素，加长的聚合物加长的ABG 在愈合过程中向手术部位的药物，并提供最佳的再生支架。我们的方法 并且应用与市场上的竞争产品不同，应为 改善患者的预后。我们的初步数据表明ABG机械强度和 在2周内从ABG释放模型分子。 在此I阶段提案中，猪ABG将用聚（乳酸 - 糖乙二醇化）（PLGA）聚合物浸渍 富含抗生素利福平和米诺环素。我们打算（a）在 体外，（b）评估产品的机械性能，以及（c）啮齿动物中产物的体内效率评估 AWR的模型。如果成功，我们将生成概念证明数据，以表明我们的抗生素和 聚合物浸渍的ABG能够减少感染并促进伤口愈合。