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

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

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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.

描述（由适用提供）：超过500,000名美国患者患有末期肾脏疾病，超过80％的患者利用血液透析作为选择的肾脏替代方式。透析患者护理中的跟腱是一种功能耐用且耐用的血管通道的发展，可以选择动静脉瘘。治疗血管通道功能障碍的年度成本超过10亿美元。这在很大程度上是由于未能成熟的动静脉瘘（AVF）的比例很高。创建后，由于早期的静脉新素元素发育和血管舒张不足，有60％的AVF无法成功使用透析。目前，尚无有效的疗法来促进血管通道成熟。内属材料开发了一种纳米质涂层，该涂层模仿天然内皮的特征性能。该纳米机可以涂在生物相容性的电纺多苯乙酮（EPCL）片上，然后在创建时将其包裹在透析AVF周围。涂层在2个月内提供了一氧化氮（NO）的持续释放，从而募集和保留内皮细胞和内皮祖细胞。它还结合了促进内皮细胞保留和迁移的内皮细胞粘附配体。 NO的持续释放还促进了健康的AVF成熟所需的适当血管舒张。这种涂层还限制了平滑肌（SMC）的增殖，这是SMC增殖在AVF不饱和中起重要作用，这是一个额外的益处。 Nanomatrix涂层是一种基于生物相容性的肽材料，可通过简单的水蒸发在EPCL板上涂层。这种涂层方法最大程度地减少了炎症反应的风险。在此I阶段SBIR中，我们建议评估和优化EPCL表的涂层。这将包括评估物理特征和评估对内皮和平滑肌细胞生长的影响。与伯明翰阿拉巴马大学李博士合作，该涂层的有效性将在既定的啮齿动物AVF模型中进行评估，并与未涂层的EPCL表进行比较。促进AVF成熟的涂层的开发可能会对需要透析的患者的治疗产生重大影响。随着第一阶段的成功完成，我们计划在第二阶段继续前进到大型动物研究。