Improving the safety and effectiveness of adhesion prevention following colorectal procedures with high risk of cancer or infection

提高癌症或感染高风险结直肠手术后预防粘连的安全性和有效性

• 批准号: 10603903
• 负责人: Timothy Joseph Keane
• 金额: $ 26.99万
• 依托单位: TYBR HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603903
• 关键词: Abdomen; Abdominal Abscess; Abscess; Address; Adhesions; Adoption; Animal Model; Animals; Anti-Bacterial Agents; Bacteria; Biological; Cancer Cell Growth; Carboxymethylcellulose; Cells; Cellulose; Cessation of life; Characteristics; Chicago; Cicatrix; Clinical; Colectomy; Collaborations; Collagen; Colon; Colon Carcinoma; Colorectal; Colorectal Cancer; Colorectal Surgery; Complication; Data; Defense Mechanisms; Development; Disease; Doctor of Philosophy; Effectiveness; Environment; Excision; Extracellular Matrix; Extravasation; FDA approved; Feces; Female infertility; Film; Gel; Growth; Health; Health Care Costs; Healthcare; High-Risk Cancer; Hospitals; Human; Hyaluronic Acid; Hydrogels; Immune; Immune response; Impaired healing; Impaired wound healing; Incidence; Infection; Infertility; Injury; Intervention; Intestinal Obstruction; Intestines; Intra-abdominal; Invertebrates; Laparoscopy; Laparotomy; Lead; Life; Life Expectancy; Liquid substance; Malignant Neoplasms; Mechanics; Medical Device; Membrane; Methods; Microbe; Modeling; Morbidity - disease rate; Mus; Natural regeneration; Neoplasm Metastasis; Operative Surgical Procedures; Oxides; Pathologic; Pathology; Patients; Peptides; Play; Positioning Attribute; Postoperative Period; Prevention; Procedures; Process; Property; Quality of life; Recurrence; Repeat Surgery; Reporting; Resistance; Risk; Role; Safety; Sepsis; Small Intestines; Solid; Sterility; Surgeon; Surgical Injuries; Surgical Models; Surgical complication; Technology; Testing; Thinness; Time; Tissues; Trauma; Universities; Work; antimicrobial; base; biomaterial development; bone; cancer cell; cancer recurrence; cell growth; chronic pain; commercialization; effective therapy; healing; high risk; hospital readmission; improved; in vivo; infection risk; microbial host; minimally invasive; mortality; negative affect; neoplastic cell; novel therapeutics; operation; pathogen; patient population; patient response; phase I trial; pre-clinical; prevent; research and development; scaffold; surgical risk; tissue repair; tumor; tumorigenesis; wound healing

Project Summary The leading cause of long-term post-operative morbidity is adhesions—which form in nearly 95% of patients following surgery. Adhesions are bands of scar tissue that contribute to the manifestation of myriad life-long complications (e.g. small bowel obstruction, infertility, and chronic pain). The annual healthcare burden from adhesions exceeds $3 billion, but options to mitigate adhesion formation are limited and flawed. Among all abdominal surgeries, the highest rate of adhesion-related complications occurs in colorectal surgery. While pathologies caused by adhesions may take months or even years to manifest clinically, colorectal surgery is also often complicated by infection (e.g., abscess formation or sepsis) and cancer tumorigenesis. The objective of this proposal is to determine the effect of our newly developed sprayable hydrogel technology for adhesion prevention in colorectal surgery within high risk surgical environments contaminated by bacteria or cancer cells. TYBR’s expertise in biomaterial development and fluid dynamics has informed the development of 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 (upon contact with tissue) forms a thin film hydrogel to prevent adhesions between adjacent tissues by acting as a mechanical barrier. ECM Spray has proven to be >75% effective at reducing the incidence and tenacity of adhesions in well-accepted small and large animal surgical models. These promising, data show effective adhesion reduction with ECM Spray where sterility is maintained, but it is unknown how ECM Spray will perform in contaminated surgeries—an at risk patient population without an effective therapy because competitor products are largely contraindicated for use in contaminated surgeries. Infection risk is a key translational challenge for adhesion barriers, which has been highlighted by past failed products, including Intergel which was removed from the market after over 100 reports of infection problems, including 3 deaths. Therefore, the objective of the present study is to determine if ECM Spray will prevent adhesion formation without increasing risk of tumorigenesis or abdominal abscess in a contaminated surgeries. In Aim 1, we will determine the effect of ECM Spray on bacterial growth. In Aim 2, we will determine the effect of ECM Spray on cancer tumorigenesis. Results of the proposed work will directly lead to a key research and development milestone towards commercialization. These results will be presented to the FDA to establish safety and efficacy of ECM Spray for use in tumor resection surgeries and non-sterile surgeries and increase the technological and commercial potential of ECM Spray. In addition, if we show potential for ECM Spray to reduce infection, this will broaden the scope for use and dramatically increase the patient and clinical impact, as well as encourage surgeon adoption in surgeries with a contaminated field.

项目概要 术后长期发病的主要原因是粘连——近 95% 的患者都会出现粘连 手术后粘连是疤痕组织带，导致无数终生的表现。 并发症（例如小肠梗阻、不孕症和慢性疼痛）。 粘连成本超过 30 亿美元，但减轻粘连形成的选择有限且各有特色。 腹部手术中，粘连相关并发症发生率最高的是结直肠手术。 由粘连引起的病理可能需要数月甚至数年才能在临床上显现，结直肠手术也 通常因感染（例如脓肿形成或脓毒症）和癌症肿瘤发生而复杂化。 该提案旨在确定我们新开发的可喷雾水凝胶技术的粘合效果 在被细菌或癌细胞污染的高风险手术环境中进行结直肠手术的预防。 TYBR 在生物材料开发和流体动力学方面的专业知识为可喷雾剂的开发提供了信息 源自细胞外基质的粘附屏障（ECM 喷雾），作为机械屏障，引发 患者自身身体的愈合反应，可防止粘连并调节组织修复。 具有热响应性并且（在与组织接触时）形成薄膜水凝胶以防止之间的粘连 已证明，ECM 喷雾可作为机械屏障，在减少邻近组织方面的效果>75%。 广泛接受的小型和大型动物手术模型中粘连的发生率和顽固性。 数据显示，ECM 喷雾可有效减少粘附，同时保持无菌状态，但尚不清楚 ECM 是如何实现的 喷雾将在受污染的手术中发挥作用——这是一个没有有效治疗的高危患者群体，因为 竞争对手的产品很大程度上禁止在受污染的手术中使用，感染风险是一个关键因素。 粘合屏障的转化挑战，过去失败的产品已经强调了这一点，包括 Intergel 在收到 100 多起感染问题报告（包括 3 例死亡）后被从市场上撤下。 因此，本研究的目的是确定 ECM Spray 是否可以防止粘附形成 在目标 1 中，我们将在不增加污染手术中发生肿瘤或腹腔脓肿的风险的情况下。 确定 ECM Spray 对细菌生长的影响 在目标 2 中，我们将确定 ECM Spray 对细菌生长的影响。 所提出的工作结果将直接导致关键的研究和开发。 这些结果将提交给 FDA 以确定安全性和有效性。 ECM Spray在肿瘤切除手术和非无菌手术中的应用，提高了技术和 ECM Spray 的商业潜力 此外，如果我们展示 ECM Spray 减少感染的潜力，这将是非常重要的。 扩大使用范围并显着增加患者和临床影响，并鼓励 外科医生在受污染区域的手术中采用。