A Novel Synthetic Vascular Graft Capable of Minimally-Invasive Controlled Expansion to Match Somatic Growth in Neonatal and Pediatric Patients

一种新型合成血管移植物，能够微创控制扩张，以匹配新生儿和儿童患者的体细胞生长

• 批准号: 9344808
• 负责人: Denver Michael Faulk
• 金额: $ 14.94万
• 依托单位: PECA LABS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9344808
• 关键词: Address; Anastomosis - action; Animal Model; Animals; Aorta; Aortic coarctation; Balloon Dilatation; Biomedical Engineering; Blood; Blood Vessels; Blood flow; Caliber; Cardiac Surgery procedures; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Cardiovascular system; Catheters; Characteristics; Chemicals; Child; Child Care; Childhood; Clinical; Clinical Trials; Complex; Descending aorta; Development; Devices; Dimensions; Domestic Pig; Endothelium; Environment; Future; Goals; Growth; Healthcare Systems; Heart Diseases; Hemolysis; Histologic; Human; Implant; In Vitro; Inductively Coupled Plasma Mass Spectrometry; Infant; Investigation; Knowledge; Lead; Life; Longevity; Mass Fragmentography; Mechanics; Modeling; Neurologic; Newborn Infant; Operative Surgical Procedures; Patients; Pediatric cardiology; Performance; Phase; Physiological; Plasticizers; Plastics; Polytetrafluoroethylene; Positioning Attribute; Postoperative Period; Procedures; Property; Quality of life; Radial; Repeat Surgery; Research; Research Project Grants; Safety; Sample Size; Site; Solvents; Spectrophotometry; Surgeon; System; Technology; Test Result; Testing; Time; Tissues; Toxic effect; Validation; Vascular Graft; biomaterial compatibility; clinically relevant; congenital heart disorder; cytotoxicity; design; experience; implantation; improved; in vivo; irritation; manufacturing process; minimally invasive; neonatal patient; new technology; novel; pediatric patients; phase 1 study; phase 2 study; pre-clinical; pre-clinical research; pressure; prototype; standard of care

PROJECT SUMMARY In pediatric cardiovascular surgery, no commercially available vascular conduit is capable of growing with the patient following implantation. This inability to grow with the patient is particularly relevant for newborns and young children because additional surgeries are required to replace the implanted conduit. In order to address this issue, PECA Labs has developed a novel cardiovascular conduit that can be expanded with a minimally invasive balloon catheter. This technology has been achieved by altering the properties of expanded Polytetrafluoroethylene (ePTFE) through a propriety manufacturing process. A prototype of PECA’s expandable conduit has successfully been developed, produced, and validated through in vitro and ex vivo preliminary studies. The overall goal of the proposed research is to gain important knowledge of the biocompatibility and in- vivo performance of this expandable ePTFE conduit (EEC). Benchtop ex-vivo testing has illustrated the functionality of the proposed EEC: resisting spontaneous expansion at normal pressures, but capable of expanding by dilation with a standard balloon catheter. Expansion to well over three times the original diameter has been demonstrated without compromising the mechanical strength. The first aim of this study is to compare the biocompatibility of pre- and post-expansion EEC to currently available and commonly used ePTFE vascular grafts. Biocompatibility testing will consist of cytotoxicity, system toxicity, hemolysis, sensitization, irritation, implantation, and USP plastics analysis. Chemical analysis of the conduit will also by conducted by using polar and non-polar solvent extractable and leachable testing with GC- MS, LC-MS, ICP-MS, and UV-Vis spectrophotometry. It is expected that the results of these tests will show that the EEC is biocompatible. The second aim is to compare the in vivo functionality and biocompatibility of PECA’s EEC with commercially available ePTFE vascular grafts in a large animal model. We will demonstrate controlled expansion of the EEC with a minimally invasive procedure. It is expected that the biocompatibility will be acceptable, and successful EEC expansion will be safely achieved. Successful realization of the aims in this proposal will allow for Phase II studies to complete longer-term preclinical research and any remaining regulatory requirements in order for this novel product to become available for newborns and growing children with congenital heart disease. Without the need for repeat surgeries to upsize conduits, thousands of children with various forms of heart disease would directly benefit from this technology, and there would also be a reduction in the burden on the healthcare system.

项目摘要 在小儿心血管手术中，没有商业可用的血管导管能够随着 植入后的患者。这种无法与患者一起成长与新生儿特别相关 幼儿是因为需要其他手术来替换植入的导管。为了解决 这个问题，Peca Labs开发了一种新颖的心血管导管，可以用最小的 侵入性气球导管。通过更改扩展的属性来实现这项技术 通过礼节制造过程，聚氟乙烯（EPTFE）。 PECA可扩展的原型 导管已通过体外和实体初步成功开发，生产和验证 研究。拟议的研究的总体目标是获得有关生物相容性和内在的重要知识 该扩展EPTFE导管（EEC）的体内性能。台式前体验测试已经说明了 提议的EEC的功能：在正常压力下抵抗自发扩张，但能够 通过标准气球导管扩散扩展。扩展到原始直径的三倍以上 已经证明了不损害机械强度的情况。 这项研究的第一个目的是将扩张前和后EEC的生物相容性与当前 可用且常用的EPTFE血管移植物。生物相容性测试将包括细胞毒性，系统 毒性，溶血，灵敏度，刺激，植入和USP塑料分析。化学分析 导管也将通过使用GC-使用极性和非极性溶解和可利用的测试来进行导管 MS，LC-MS，ICP-MS和UV-VIS分光光度法。预计这些测试的结果将表明 EEC是生物相容性的。 第二个目的是比较PECA的EEC的体内功能和生物相容性与商业上 大型动物模型中可用的EPTFE血管移植物。我们将展示EEC的受控扩展 使用最小的侵入性程序。预计生物相容性将是可以接受的，并且成功 EEC扩展将被安全实现。在该提案中成功实现目标将允许第二阶段 完成长期临床前研究和任何剩余的监管要求的研究 新生儿可用于新生儿和成长中先天性心脏病的儿童。没有 需要重复手术以升级指导，成千上万的患有各种形式的心脏病的儿童将 直接受益于这项技术，并且医疗保健系统上的伯恩（Burnen）也会减少。