Characterization of the Effect of an ECM Based Adhesion Barrier on Healing of Bowel Anastomoses

基于 ECM 的粘连屏障对肠吻合愈合效果的表征

• 批准号: 10325229
• 负责人: Timothy Joseph Keane
• 金额: $ 25.6万
• 依托单位: TYBR HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-11 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325229
• 关键词: Abdomen; Address; Adhesions; Adoption; Affect; Anastomosis - action; Animal Model; Bacteria; Carboxymethylcellulose; Cells; Chicago; Chronic; Cicatrix; Clinical; Collaborations; Collagen; Colon; Colorectal; Colorectal Cancer; Colorectal Surgery; Complex; Diverticulitis; Doctor of Philosophy; Epithelial; Esophagus; Excision; Extracellular Matrix; Extravasation; Film; Gel; Gynecologic; Health; Health Care Costs; Healthcare; High Fat Diet; Hyaluronic Acid; Hydrogels; Immune response; Impaired healing; Impaired wound healing; In Vitro; Incidence; Infection; Infertility; Inflammatory Bowel Diseases; Injury to Peritoneum; Instruction; Intervention; Intestinal Obstruction; Intestines; Lead; Life; Liquid substance; Mammalian Oviducts; Mechanics; Medical Device; Methodology; Methods; Microbe; Modeling; Morbidity - disease rate; Mus; Nerve; Operative Surgical Procedures; Organism; Oryctolagus cuniculus; Patients; Pelvis; Peritoneum; Physiological; Positioning Attribute; Postoperative Period; Prevention; Procedures; Process; Property; Recovery; Repeat Surgery; Research; Safety; Signal Transduction; Site; Small Intestines; Solid; Structure; Surgeon; Surgical Injuries; Surgical complication; Testing; Therapeutic; Thinness; Time; Tissues; Universities; Work; antimicrobial; base; bone; chronic pain; chronic pelvic pain; collagenase; critical period; healing; high risk; improved; in vivo; intestine surgery; minimally invasive; mortality; mouse model; novel; novel strategies; operation; opioid use; patient response; preclinical study; prevent; repaired; research and development; response; restoration; safety and feasibility; safety testing; scaffold; tissue repair; wound healing

Project Summary Over 7 million abdominal and pelvic operations are performed each year in the US and adhesions—the leading cause of post-operative morbidity—form in nearly 90% of patients following these surgeries. Adhesions are bands of scar tissue that contribute to the manifestation of myriad life-long complications (e.g., chronic pelvic pain, small bowel obstruction, and infertility) and the annual healthcare burden exceeds $2.5 billion, but current options to mitigate adhesion formation are limited and flawed. Based on nearly a decade of research, we have developed a sprayable adhesion barrier derived from extracellular matrix (ECM Spray), which serves as a mechanical barrier that elicits a healing response from the patient’s own body to prevent adhesions and regulate tissue repair. The ECM Spray is thermally responsive and forms a thin film hydrogel over the tissue where it’s applied and prevents adhesions by acting as a mechanical barrier between adjacent tissues. In two separate pre-clinical studies using validated small and large animal models, post-operative application of ECM Spray has resulted in >75% reduction in adhesion incidence and tenacity. A major limitation of currently available adhesion barriers is that they are contraindicated for use in procedures that involve a bowel resection and re-connection (i.e., bowel anastomosis) because the adhesion barriers have been shown to inhibit healing which can cause leakage. Interestingly, we’ve shown that when applied to surgically injured peritoneum, ECM Spray acts as a scaffold to support re-epithelialization and healing of the peritoneum. However, it is unknown how ECM Spray will interact with more complex wound healing processes which occur in intestinal anastomosis procedures. Therefore, the objective of the present study is to determine the efficacy of ECM Spray’s for preventing adhesions while safely maintaining bowel healing following anastomosis procedures. In Aim 1, we will determine the efficacy of ECM Spray on adhesion prevention and characterize the effect of ECM Spray on intestinal healing. In Aim 2, we will determine whether ECM Spray may promote anastomotic healing in a high-risk model of intestinal repair. Results of the proposed work will lead to a key research and development milestone necessary for establishing safety and efficacy of ECM Spray for use in abdominal and pelvic operations and increase the technological and commercial potential of ECM Spray. In addition, if we show potential for ECM Spray to limit anastomotic leaks, this will broaden the scope for use and dramatically increase the patient and clinical impact, as well as encourage surgeon adoption in colorectal surgeries.

项目概要 美国每年进行超过 700 万例腹部和盆腔手术，而粘连是最主要的手术 近 90% 的手术后患者出现术后并发症。粘连是 疤痕组织带导致无数终生并发症的表现（例如慢性盆腔炎） 疼痛、小肠梗阻和不孕症），每年的医疗负担超过 25 亿美元，但目前 减轻粘附形成的选择是有限的并且存在缺陷。基于近十年的研究，我们 开发了一种源自细胞外基质的可喷雾粘附屏障（ECM Spray），可作为 机械屏障，引起患者自身的愈合反应，以防止粘连并调节 组织修复。 ECM 喷雾具有热响应性，并在其所在的组织上形成薄膜水凝胶 通过充当相邻组织之间的机械屏障来防止粘连。在两个单独的 使用经过验证的小型和大型动物模型进行的临床前研究，ECM Spray 的术后应用 导致粘连发生率和韧性降低 75% 以上。目前可用的粘附力的主要限制 障碍是它们禁忌用于涉及肠切除和重新连接的手术 （即肠吻合术），因为粘连屏障已被证明会抑制愈合，从而导致 泄漏。有趣的是，我们已经证明，当应用于手术损伤的腹膜时，ECM Spray 可以充当 支持腹膜再上皮化和愈合的支架。然而，目前尚不清楚ECM Spray如何 将与肠吻合手术中发生的更复杂的伤口愈合过程相互作用。 因此，本研究的目的是确定 ECM Spray 预防感染的功效 粘连，同时在吻合手术后安全地维持肠道愈合。在目标 1 中，我们将确定 ECM Spray 对预防粘连的功效并表征 ECM Spray 对肠道愈合的影响。 在目标 2 中，我们将确定 ECM Spray 是否可以促进高风险模型中的吻合口愈合 肠道修复。拟议工作的结果将导致必要的关键研发里程碑 确定 ECM Spray 在腹部和骨盆手术中使用的安全性和有效性，并提高 ECM Spray 的技术和商业潜力。此外，如果我们显示 ECM Spray 有潜力限制 吻合口漏，这将扩大使用范围并显着增加对患者和临床的影响， 并鼓励外科医生在结直肠手术中采用。