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.

项目摘要 手术后长期并发症的主要原因是粘连--在近95%的患者中形成粘连 在手术后。粘连是疤痕组织的带状组织，有助于表现出无数的终生 并发症(如小肠梗阻、不孕症和慢性疼痛)。每年的医疗负担来自 粘连超过30亿美元，但缓解粘连形成的选择有限且存在缺陷。最重要的是 腹部手术中，粘连相关并发症发生率最高的是结直肠手术。而当 粘连引起的病理可能需要几个月甚至几年的时间才能在临床上表现出来，结直肠手术也是如此 通常并发感染(例如，脓肿形成或败血症)和癌症肿瘤形成。的目标是 这项建议是为了确定我们新开发的可喷雾水凝胶粘合技术的效果。 在受细菌或癌细胞污染的高危手术环境中预防结直肠手术。 TYBR在生物材料开发和流体动力学方面的专业知识推动了可喷雾材料的开发 来自细胞外基质的黏附屏障(ECM喷雾)，作为一种机械屏障，可诱导 患者自身的愈合反应，以防止粘连和调节组织修复。ECM喷雾 是热响应的，(与组织接触时)形成一种薄膜水凝胶，以防止 通过起到机械屏障的作用来保护邻近的组织。ECM喷雾已被证明是&>75%有效地减少 在公认的小动物和大动物手术模型中粘连的发生率和韧性。这些前景看好的， 数据显示，在保持无菌的情况下，使用ECM喷雾可以有效减少粘连，但ECM是如何减少粘连的尚不清楚 喷雾将在受污染的手术中发挥作用-没有有效治疗的高危患者群体，因为 竞争对手的产品在很大程度上被禁止用于受污染的手术。感染风险是关键 粘合障碍的翻译挑战，过去失败的产品强调了这一点，包括 InterGel在100多起感染问题报告后被从市场上撤下，其中包括3人死亡。 因此，本研究的目的是确定ECM喷雾是否能防止粘连的形成 而不会增加受污染手术中肿瘤形成或腹壁脓肿的风险。在目标1中，我们将 确定ECM喷雾对细菌生长的影响。在目标2中，我们将确定ECM喷雾对 癌症发生学。拟议工作的成果将直接导致一项关键的研究和开发 迈向商业化的里程碑。这些结果将提交给FDA以确定安全性和有效性 在肿瘤切除手术和非无菌手术中使用ECM喷雾，并增加技术和 ECM喷雾的商业潜力。此外，如果我们显示出ECM喷雾减少感染的潜力，这将 扩大使用范围，极大地增加患者和临床影响，并鼓励 外科医生在受污染场地的外科手术中的采用。