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.

项目摘要 每年在美国和广告中进行超过700万个腹部和骨盆操作，这是领先的 术后发病率的原因 - 这些手术后，几乎90％的患者中有几乎90％。粘连是 疤痕组织的带，导致无数终身并发症的表现（例如，慢性骨盆 疼痛，小肠异议和不育）和年度医疗保健烧伤超过25亿美元，但目前 减轻广告形成的选项有限且缺陷。根据将近十年的研究，我们有 开发了一种衍生自细胞外基质（ECM喷雾）的可喷涂粘膜，该屏障用作 机械障碍会引起患者自身身体的愈合反应，以防止粘附和调节 组织修复。 ECM喷雾具有热响应，并在其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应用并防止粘附。在两个分开 使用经过验证的大小动物模型的临床前研究，ECM喷雾的术后应用具有 导致粘合性发生率和韧性降低> 75％。当前可用粘合剂的主要限制 障碍是禁忌用于涉及肠切除和重新连接的程序 （即肠吻合），因为已证明粘附屏障会抑制愈合，这可能导致 泄漏。有趣的是，我们已经表明，当应用于手术受伤的腹膜时，ECM喷雾充当 脚手架支持腹膜的重新上皮化和愈合。但是，尚不清楚ECM如何喷涂 将与肠道吻合程序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喷雾的效率 在吻合程序后安全保持肠愈合的同时，粘附。在AIM 1中，我们将确定 ECM喷雾对预防广告的有效性以及ECM喷雾对肠道愈合的影响。 在AIM 2中，我们将确定ECM喷雾是否可以在高风险模型中促进吻合术的愈合 肠道修复。拟议的工作的结果将导致必要的关键研发里程碑 为了建立ECM喷雾的安全性和效率，用于腹部和骨盆操作，并增加 ECM喷雾的技术和商业潜力。此外，如果我们显示出ECM喷雾的潜力 吻合式泄漏，这将扩大使用范围，并大大增加患者和临床影响， 以及鼓励外科医生在结直肠手术中采用。