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 长期术后发病率的主要原因是广告 - 几乎95％的患者形成了广告 手术后。粘附是疤痕组织的带，有助于无数终身的表现 并发症（例如小肠异议，不育和慢性疼痛）。一年一度的医疗保健烧伤 粘连超过30亿美元，但是减轻广告形成的选择是有限且缺陷的。全部 腹部手术，与粘合剂有关的并发症发生率最高，发生在结直肠手术中。尽管 广告引起的病理可能需要数月甚至数年的时间才能在临床上表现出来，大肠手术也是 通常因感染（例如脓肿形成或败血症）和癌症肿瘤发生而复杂。目的 该建议是确定我们新开发的可喷雾水凝胶技术对广告的影响 在高风险外科手术环境中预防结直肠手术，受细菌或癌细胞污染的预防。 Tybr在生物材料开发和流体动力学方面的专业知识已为开发提供了可喷涂的 源自细胞外基质（ECM喷雾）的粘附屏障，它是引起的机械屏障 患者自己的身体的愈合反应，以防止粘附并调节组织修复。 ECM喷雾 具有热响应性，（与组织接触时）形成薄膜水凝胶，以防止粘合剂 通过充当机械屏障，相邻组织。事实证明，ECM喷雾在减少降低的有效效果> 75％> 75％ 在经过良好接受的大小动物外科手术模型中，依从性的发病率和坚韧。这些承诺， 数据显示有效的粘附在维持不育的ECM喷雾剂中降低，但尚不清楚ECM如何 喷雾剂将在受污染的手术中进行 - 在没有有效疗法的情况下处于风险的患者人群中，因为 竞争对手产品在很大程度上禁忌用于污染的手术。感染风险是关键 广告障碍的转化挑战，该广告障碍已被过去的失败产品强调，包括 经过100多个感染问题的报告，包括3例死亡。 因此，本研究的目的是确定ECM喷雾是否会防止粘合剂形成 在受污染的手术中，没有增加肿瘤发生或腹部脓肿的风险。在AIM 1中，我们将 确定ECM喷雾对细菌生长的影响。在AIM 2中，我们将确定ECM喷雾对 癌症肿瘤发生。拟议工作的结果将直接导致关键的研发 商业化的里程碑。这些结果将提交给FDA以建立安全和效率 ECM喷雾剂用于肿瘤切除手术和非疾病手术，并增加技术和 ECM喷雾的商业潜力。另外，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，并大大增加患者和临床影响，并鼓励 外科医生在受污染领域的手术中收养。