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 在儿科心血管外科手术中，没有市售的血管导管能够随着血管的生长而生长。 植入后患者。这种不能与患者一起成长的情况尤其与新生儿有关， 因为需要额外的手术来替换植入的管道。为了解决 在这个问题上，PECA实验室已经开发出一种新型的心血管管道， 侵入性球囊导管。这项技术是通过改变膨胀的 聚四氟乙烯（ePTFE）通过适当的制造工艺。PECA的可扩展原型 通过体外和离体初步试验， 问题研究拟议研究的总体目标是获得生物相容性的重要知识， 该可膨胀ePTFE导管（EEC）的体内性能。实验室离体试验表明， 拟议EEC的功能：在正常压力下抵抗自发膨胀，但能够 通过用标准球囊导管扩张而扩张。膨胀到原始直径的三倍以上 已被证明不会损害机械强度。 本研究的第一个目的是比较扩张前和扩张后EEC的生物相容性， 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、致敏、刺激、植入和USP塑料分析。的化学分析 导管也将通过使用极性和非极性溶剂浸提物和沥滤物试验进行GC- 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是生物相容的。 第二个目的是比较PECA的EEC与市售EEC的体内功能性和生物相容性。 在大型动物模型中使用可用的ePTFE血管移植物。我们将证明欧洲经济共同体的有控制的扩张 通过微创手术。预计生物相容性将是可接受的并且是成功的 EEC扩张将安全实现。成功实现本提案中的目标将使第二阶段 完成长期临床前研究的研究和任何剩余的监管要求，以便 新的产品，成为可用于新生儿和成长中的儿童先天性心脏病。未经 由于需要重复手术来扩大管道，成千上万患有各种心脏病的儿童将 直接受益于这项技术，也将减轻医疗保健系统的负担。