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Development of Silk Fibroin Grafts for Reconstruction of Pathological Bladders

用于病理性膀胱重建的丝素蛋白移植物的开发

基本信息

批准号：
9105758
负责人：
Carlos R Estrada
金额：
$ 26.55万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-06 至 2017-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9105758
关键词：
Adverse effects Affect Animal Model Anti-Inflammatory Agents Anti-inflammatory Autologous Benign Benign Prostatic Hypertrophy Biocompatible Materials Bladder Bladder Diseases Bladder Tissue Bladder neck obstruction Cells Characteristics Chronic Cicatrix Defect Development Equilibrium Etiology Family suidae Fibroins Functional disorder Genitourinary system Goals Gold Health Human Immune response Implant Inflammatory Interleukin-1 beta Interleukin-10 Interleukin-13 Interleukin-4 Interleukin-6 Intestinal Obstruction Intestines Kidney Failure Knowledge Macrophage Activation Mechanics Mediator of activation protein Medical Metabolic Modeling Mucous body substance Muscle NOS2A gene Nature Neurogenic Bladder Obstruction Operative Surgical Procedures Organ Outcome Patients Perforation Performance Phenotype Play Polyesters Process Production Property Psychological reinforcement Quality of life Recurrence Regenerative response Renal function Reporting Role Secondary to Serious Adverse Event Silk Site Sphincter Spinal Spinal cord injury Stimulus System Techniques Technology Testing Tissue Engineering Tissues Transforming Growth Factors Translating Urethra Urinary Calculi Urinary Incontinence Urinary tract Urinary tract infection Urodynamics Variant Visceral Wound Healing angiogenesis arginase base clinical practice cytokine design functional outcomes functional plasticity gastrointestinal implantation improved intravesical macrophage patient safety pressure programs reconstruction regenerative repaired research study scaffold tissue regeneration tissue repair urinary urinary bladder neck urinary tract obstruction urologic

项目摘要

DESCRIPTION (provided by applicant): Congenital and acquired urologic abnormalities including neurogenic bladder secondary to spinia bifida or spinal cord injury, posterior urethral valves, and benign prostatic hyperplasia frequently result in urinary tract obstruction which ultimately leads to diminished bladder capacity and poor compliance. Urinary incontinence, recurrent urinary tract infections, and renal failure are debilitating consequences of obstructive bladder diseases. Enterocystoplasty is utilized as the primary approach to increase bladder capacity and decrease high intravesical pressures in order to preserve renal function in patients afflicted with pathological bladder obstruction. However, the long term efficacy of this technique is hampered by frequent and severe complications which negatively impact patient quality of life. Silk fibroin (SF)-based implants provide an exceptional combination of physical characteristics that are well suited to support bladder function. Therefore, these scaffolds may overcome the deleterious side-effects associated with enterocystoplasty and serve as an "off the shelf" graft for bladder reconstruction. Given the role of M2 macrophage activation in orchestrating regenerative responses, we anticipate that SF scaffolds which can promote an M2 phenotype during defect consolidation will be beneficial in improving pathological bladder performance. In this proposal, we will test the overall hypothesis that: bladder augmentation with SF biomaterials capable of delivering pro-M2 macrophage activation factors (IL-4, IL-13) will serve as a superior approach for improving pathological bladder function in comparison to enterocystoplasty. The specific aims of the application are: Specific Aim 1: Determine the impact of SF scaffold properties on constructive remodeling and organ function following augmentation cystoplasty in a porcine model of partial bladder outlet obstruction. Specific Aim 2: Evaluate the utility of SF-based, IL-4/IL-13-delivery systems to induce M2 macrophage activation, enhance constructive remodeling, and improve obstructed bladder function.