Healing enterocutaneous fistulas using bioengineered biomaterials

使用生物工程生物材料治愈肠皮瘘

• 批准号: 10384769
• 负责人: Ali Khademhosseini
• 金额: $ 59.16万
• 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/10384769
• 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; 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; Interventional Imaging; Intestines; 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; 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; base; biomaterial compatibility; follow-up; healing; image guided; implantation; improved; in vitro testing; in vivo; in vivo Model; mechanical properties; microCT; minimally invasive; mortality; prevent; programs; 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.

摘要