Healing enterocutaneous fistulas using bioengineered biomaterials

使用生物工程生物材料治愈肠皮瘘

• 批准号: 10532787
• 负责人: Ali Khademhosseini
• 金额: $ 57.29万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10532787
• 关键词: Adhesives; Biocompatible Materials; Biological Markers; Biomedical Engineering; Blood; Blood Banks; Blood Platelets; Catheters; Chemicals; Chronic; Clinic; Clinical; Collaborations; Colon; Colorectal; Complex; Coupled; Creativeness; Data; Engineering; Ensure; Enteral; Enterocutaneous Fistula; Extravasation; Failure; Family suidae; Feces; Fibrin; Fistula; Fluoroscopy; Formulation; Gel; Growth Factor; Health Care Costs; Histology; Hydrogels; Image; Imaging technology; In Vitro; Incontinence; Infection; Inflammation; Injectable; Intensive Care Units; Intervention; Intestines; Intra-abdominal; Irritants; Lead; Literature; Magnetic Resonance Imaging; Malnutrition; Medical; Mental Depression; Modeling; Morbidity - disease rate; Morphologic artifacts; Neck; Operative Surgical Procedures; Organ; Outcome Measure; Pain; Pancreatic enzyme; Patients; Peptide Hydrolases; Performance; Population; Postoperative Period; Pre-Clinical Model; Predisposition; Property; Proteins; Pus; Quality of life; RNA; Radiation; Rattus; Recurrence; Rodent; Roentgen Rays; Silicates; Skin; Slide; Small Intestines; Stomach Content; Surgeon; Surgical complication; Techniques; Testing; Therapeutic Effect; Thinness; Time; Tissues; Treatment Efficacy; Visit; X-Ray Computed Tomography; X-Ray Medical Imaging; adhesive polymer; animal data; antimicrobial; biomaterial compatibility; follow-up; healing; image guided; implantation; improved; in vitro testing; in vivo; in vivo Model; mechanical properties; microCT; minimally invasive; mortality; nano; prevent; regenerative; seal; skills; subcutaneous; transcriptome sequencing; ultrasound; wound care

Abstract Enterocutaneous fistula (ECF) is an abnormal connection between the bowel and skin. It can be associated with discharge of pus, feces, and stomach contents and can even lead to incontinence. ECFs are referred to as surgical tragedies in the literature, as up to 85% are the result of intraabdominal surgical complications, such as missed enterotomies or anastomotic leaks. This can lead to constant leakage of enteric and fecal contents from the skin, sometimes up to many liters per day. The foul enteric contents act as a chemical irritant to the skin, leading to skin breakdown and predisposition to infection. Despite advances in treatment, ECFs still account for significant mortality of 15-20% and are associated with debilitating morbidity and substantially poor quality of life due to complex wound care, severe malnutrition, frequent infectious complications, pain, and depression. Despite advances in surgical techniques and postoperative management, no successful treatment of ECF exists today. The current treatment paradigm is unsuccessful; high fistula discharge, infection, and chronic inflammation lead to high failure and recurrence rates. This often results in prolonged intensive care unit (ICU) stays increasing health care cost which can be over $500,000 per ICU visit. We hypothesize that by using a bioengineered biomaterial that is biocompatible, non-toxic, durable, antimicrobial and regenerative, we would change the standard of medical practice in the approach to ECF. This creative approach may reduce world-wide morbidity and mortality by successfully occluding and healing any ECF, preventing fecal leakage; it will also substantially improve the quality of life of the patient and reduce the need for repeated interventions and X-ray imaging. We aim to make a paradigm shift in the treatment of potentially fatal ECF using a minimally invasive blood-derived biomaterial-based platform to occlude the fistulous tract using groundbreaking injectable shear- thinning platelet-rich gels. We will engineer the blood derived biomaterial to include antimicrobial, adhesive, and regenerative components that will be tested in vitro and in vivo (Aim 1) and we will evaluate the optimized biomaterial with established rodent fistula models (Aim 2). Finally, we will test theses engineered biomaterials in a porcine ECF model to promote aseptic healing of fistulas (Aim 3). We will evaluate healing trajectories of the fistulas using clinical observation, fluoroscopy, ultrasound, micro-CT, histology, Helios mass cytometer analysis of the cellular populations and the Hyperion imaging technology to evaluate up to 37 biomarkers on slides and RNA sequencing.

抽象的 肠面瘘（ECF）是肠和皮肤之间的异常连接。它可以与 脓，粪便和胃含量的排放，甚至可能导致尿失禁。 ECF被称为 文献中的手术悲剧，因为多达85％是腹部手术并发症的结果，例如 错过的肠肠或吻合泄漏。这可能导致肠和粪便中的持续泄漏 皮肤，有时每天多升。肮脏的肠内容物充当对皮肤的化学刺激性， 导致皮肤崩溃和感染易感性。尽管治疗进展，但ECF仍在解释 显着死亡率为15-20％，与发病率衰弱和生活质量差有关 由于伤口复杂，营养不良，频繁的感染并发症，疼痛和抑郁症。 尽管手术技术和术后管理方面取得了进步，但对ECF的成功治疗尚无 今天。当前的治疗范式没有成功；高瘘管排出，感染和慢性 炎症导致高失败和复发率。这通常会导致重症监护病房（ICU）长时间 保持医疗保健费用增加，每次ICU访问可能超过500,000美元。我们通过使用一个 生物相容性，无毒，耐用，抗菌和再生的生物工程生物材料，我们将 在ECF方法中更改医疗实践的标准。这种创造性的方法可能会减少全球 通过成功阻断和愈合任何ECF，防止粪便泄漏来发病和死亡。它也会 大大改善了患者的生活质量，并减少了重复干预和X射线的需求 成像。我们的目标是使用微创的范式进行范式转移潜在致命的ECF的治疗 基于血液的生物材料平台，可使用突破性的注射剪切 - 稀薄的血小板浓密的凝胶。我们将设计血液衍生的生物材料，包括抗菌，粘合剂和 将在体外和体内测试的再生组件（AIM 1），我们将评估优化的 具有固定啮齿动物瘘模型的生物材料（AIM 2）。最后，我们将测试这些工程的生物材料 猪ECF模型，可促进瘘管的无菌愈合（AIM 3）。我们将评估 使用临床观察，荧光镜，超声，微CT，组织学，HELIOS质量细胞仪分析的瘘管 在幻灯片和 RNA测序。