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

基本信息

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
项目类别：
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

项目摘要

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% 的手术后患者出现粘连。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，但目前根据近十年的研究，减少粘连形成的选择有限且各有特色。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 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。应用并通过充当相邻组织之间的机械屏障来防止粘连。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，这是目前可用粘连的主要限制。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，从而导致暗示性的是，我们已经证明，当应用于手术损伤的腹膜时，ECM 喷雾剂可以起到渗漏的作用。然而，ECM Spray 如何支持腹膜的上皮化和愈合尚不清楚。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 预防感染的功效在目标 1 中，我们将确定吻合术后安全维持肠道愈合的粘连情况。 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的拟议工作结果将导致必要的关键研究和开发里程碑。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 的潜力会受到限制。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。