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Nitric oxide releasing nanomatrix wrap to enhance dialysis fistula maturation

释放一氧化氮的纳米基质包裹促进透析瘘管成熟

基本信息

批准号：
9139005
负责人：
Patrick Hwang
金额：
$ 42.95万
依托单位：
ENDOMIMETICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2017-08-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9139005
关键词：
Address Adhesions Adhesives Affect Agreement Alabama Anastomosis - action Animals Arteriovenous fistula Biocompatible Blood Cells Blood Vessels Blood flow Caring Catheters Cell Proliferation Cells Characteristics Clinical Collaborations Data Development Dialysis patients Dialysis procedure Elements End stage renal failure Endothelial Cells Endothelium Evaluation Fiber Fistula Functional disorder Hemodialysis Histologic Human Hyperplasia In Vitro Inflammation Inflammatory Response Kidney Legal patent Letters Ligands Mediating Methodology Methods Modality Modeling Morbidity - disease rate Nitric Oxide Organic solvent product Patients Pattern Peptides Phase Play Positioning Attribute Preparation Production Property Rattus Recruitment Activity Research Research Infrastructure Resources Risk Rodent Role Site Small Business Innovation Research Grant Smooth Muscle Smooth Muscle Myocytes Stem cells Therapeutic Time Tissues Ultrasonography Umbilical vein United States Food and Drug Administration Universities Vascular remodeling Vasodilation Venous Water Work base cell growth clinical care cost effective therapy evaporation improved in vivo industry partner innovation migration mortality nanofiber novel phase 1 study polycaprolactone prevent public health relevance quality assurance scale up

项目摘要

DESCRIPTION (provided by applicant): More than 500,000 U.S. patients have end stage renal disease and over 80% utilize hemodialysis as their renal replacement modality of choice. The Achilles Heel in the care of dialysis patients is the development of a functioning and durable vascular access, preferably an arteriovenous fistula. The annual cost of treating vascular access dysfunction totals over one billion US dollars. This is largely due to the high proportion of arteriovenous fistulas (AVFs) that fail to mature. After creation, sixty percent of AVFs fail to mature successfully for dialysis use, due to early venous neointimal development and inadequate vasodilation. At present, there are no effective therapies to promote vascular access maturation. Endomimetics has developed a nanomatrix coating that mimics the characteristic properties of native endothelium. This nanomatrix can be coated on biocompatible electrospun polycaprolactone (ePCL) sheets that are then wrapped around the dialysis AVF at the time of creation. The coating provides sustained release of nitric oxide (NO) over 2 months, thus recruiting and retaining endothelial cells and endothelial progenitor cells. It also incorporates a endothelial cell adhesive ligand that promotes endothelial cell retention and migration. The sustained release of NO also promotes appropriate vasodilation necessary for healthy AVF maturation. This coating also limits smooth muscle (SMC) proliferation, an additional benefit since SMC proliferation plays a significant role in AVF non-maturation. The nanomatrix coating is a biocompatible peptide based material and is coated on ePCL sheets by simple water evaporation. This coating method minimizes the risk of inflammatory responses. In this Phase I SBIR, we propose to evaluate and optimize the coating for ePCL sheets. This will include evaluation of physical characteristics and assessing effects on endothelial and smooth muscle cell growth. In collaboration with Dr. Lee at the University of Alabama at Birmingham, the efficacy of this coating will be evaluated in an established rodent AVF model, and compared with non-coated ePCL sheets. Development of a coating that promotes AVF maturation may have significant impact in the treatment of patients requiring dialysis. With successful completion of Phase I, we plan to move forward in Phase II to large animal studies.