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

• 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
• 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

 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（由申请人提供）：超过 500,000 名美国患者患有终末期肾病，超过 80% 的患者选择血液透析作为肾脏替代治疗方式。护理透析患者的致命弱点是建立功能齐全且耐用的血管通路。 ，最好是动静脉瘘，每年治疗血管通路功能障碍的费用总计超过10亿美元，这很大程度上是由于动静脉瘘的比例很高。未能成熟的动静脉瘘 (AVF) 由于静脉新生内膜发育早期和血管舒张不足，60% 的动静脉瘘在创建后未能成功成熟。开发了一种模拟天然内皮特性的纳米基质涂层，这种纳米基质可以涂覆在生物相容性静电纺丝聚己内酯上。 (ePCL) 片材，然后在创建时包裹在透析 AVF 上，该涂层可在 2 个月内持续释放一氧化氮 (NO)，从而招募和保留内皮细胞和内皮祖细胞。促进内皮细胞保留和迁移的粘附配体 NO 的持续释放也促进健康 AVF 成熟所需的适当血管舒张。 (SMC) 增殖，这是一个额外的好处，因为 SMC 增殖在 AVF 不成熟中发挥着重要作用。纳米基质涂层是一种生物相容性肽基材料，通过简单的水蒸发涂覆在 ePCL 片上，这种涂层方法可最大限度地降低炎症反应的风险。在第一阶段 SBIR 中，我们建议与 Lee 博士合作评估和优化 ePCL 片材的涂层，其中包括评估物理特性以及评估对内皮细胞和平滑肌细胞生长的影响。阿拉巴马大学伯明翰分校将在已建立的啮齿动物 AVF 模型中评估这种涂层的功效，并与未涂层的 ePCL 片材进行比较，开发一种促进 AVF 成熟的涂层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，我们计划进入第二阶段的大型动物研究。