SBIR-STTR Award

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.

Public Health Relevance Statement:
PROJECT NARRATIVE Vascular conduits are frequently used by cardiovascular surgeons in infants and young children with congenital heart disease. However, repeat surgery to upsize is inevitable in order to keep up with patient growth. A vascular conduit that can undergo future expansion without repeat invasive surgery would be a major advancement in the standard of care for children with heart disease. In order to address this, PECA Labs has developed an expandable conduit. The proposed Phase I research project combines expertise in biomedical engineering, pediatric cardiac surgery, and pediatric cardiology in order to further develop this device.

Project Terms:
Address; Anastomosis - action; Animal Model; Animals; Aorta; Aortic coarctation; Balloon Dilatation; Biocompatible; biomaterial compatibility; Biomedical Engineering; Blood; Blood flow; Blood Vessels; Caliber; Cardiac Surgery procedures; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Cardiovascular system; Catheters; Characteristics; Chemicals; Child; Child Care; Childhood; Clinical; Clinical Trials; clinically relevant; Coenzyme A; commercialization; Complex; congenital heart disorder; cytotoxicity; Descending aorta; design; Development; Devices; Dimensions; Domestic Pig; Endothelium; Environment; experience; Future; Goals; Growth; Healthcare Systems; Heart Diseases; Hemolysis; Histologic; Human; Implant; implantation; improved; In Vitro; in vivo; Inductively Coupled Plasma Mass Spectrometry; Infant; Investigation; irritation; Knowledge; Lead; Life; Longevity; manufacturing process; Mass Fragmentography; Mechanics; minimally invasive; Modeling; neonatal patient; Neurologic; new technology; Newborn Infant; novel; Operative Surgical Procedures; Patients; Pediatric cardiology; pediatric patients; Performance; Phase; phase 1 study; phase 2 study; Physiological; Plasticizers; Plastics; Polytetrafluoroethylene; Positioning Attribute; Postoperative Period; pre-clinical; pre-clinical research; Pre-Post Tests; pressure; Procedures; Property; prototype; Quality of life; Radial; Repeat Surgery; Research; Research Project Grants; S-Adenosylmethionine; Safety; Sample Size; Site; Spectrophotometry; standard of care; Surgeon; System; Technology; Test Result; Testing; Time; Tissues; Toxic effect; Validation; Vascular Graft

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 benchtop, biocompatibility, and in vivo studies as well as successful achievement of CE Mark clearance for peripheral vascular use. Previous testing has illustrated the functionality of the proposed expandable ePTFE conduit (EEC), including resisting spontaneous expansion at normal pressures, yet being 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. Furthermore, the applications of the technology are not limited to pediatric cardiovascular use, but also may provide significant benefits as a valved conduit and as a conduit for peripheral vascular reconstruction in adults. This significantly increases the market size and impact of the graft and with successful completion of benchtop, biocompatibility, and in vivo testing goals in Phase I. PECA Labs proposes the three specific aims to study the EEC in long term models – central vascular reconstruction with growth, valved conduit reconstruction, and peripheral vascular reconstruction. Specific Aim 1: The goal of this aim is to study two-stage expansions as well as to compare expansions of EEC with and without the use of covered stents. Additionally, it is valuable to understand two stages of expansion, observe overall large animal health post-first expansion, and to assess compatibility of covered stents with the EEC. Specific Aim 2: The goal of this aim is to use a valved configuration of the EEC to create the first valved conduit capable of providing growth potential, achieved by expanding the valved conduit and observing its functionality in conjunction with a commercially-available transcatheter valve. This application has the potential to reduce the number of repeat open-heart surgeries by three or more over the lifetime of the child. The design of these versions is derived from a clinically-proven valved conduit design, including the proprietary intellectual property licensed by PECA Labs. Specific Aim 3: The goal of this aim is to understand the benefits of EEC in adult peripheral vascular reconstruction. This will be achieved by comparing the implanted EEC with a gold-standard vascular graft for peripheral reconstruction and assessing the benefits of expansion to lengthen the overall time for which a peripheral graft can last in adult patients.

Public Health Relevance Statement:
PROJECT NARRATIVE The inability for standard conduits used in pediatric congenital heart disease reconstructions to match somatic growth, and the recurrent interventions needed in adult peripheral vascular reconstructions, has long been a major hurdle for cardiovascular surgeries. PECA Labs has developed a novel expandable expanded- polytetrafluoroethylene (ePTFE) cardiovascular conduit that can be expanded with a minimally-invasive balloon catheter and has successfully been produced and validated through benchtop, biocompatibility, and in vivo studies. In this Phase II grant, PECA Labs now proposes three specific aims to study the EEC in long-term models for three distinctive indications – central vascular reconstruction with growth, valved conduit reconstruction, and peripheral vascular reconstruction.

Project Terms:
Achievement; Address; Adult; Adverse event; age group; analog; Animal Model; Animals; Anxiety; Aorta; Balloon Dilatation; biomaterial compatibility; Blood Vessels; Caliber; Cardiac Surgery procedures; Cardiovascular Surgical Procedures; Cardiovascular system; Catheters; Chemicals; Child; Childhood; Clinical; Clinical Trials; commercialization; Complex; congenital heart disorder; Data; Deposition; Descending aorta; design; Devices; Economic Burden; Embolism; Endothelium; Etiology; Event; experience; Failure; Family suidae; femoral artery; follow-up; Goals; Gold; Goretex; Grant; Growth; Health; Health Care Costs; homograft; Human; Implant; implantation; in vivo; in vivo evaluation; Institutes; Intellectual Property; Intervention; manufacturing process; Mechanics; migration; minimally invasive; Modeling; Newborn Infant; novel; Obstruction; Operative Surgical Procedures; Parents; Pathway interactions; Patients; Peripheral; Personal Satisfaction; Phase; phase 1 study; Polytetrafluoroethylene; Population; Postoperative Period; preclinical study; pressure; Property; prototype; reconstruction; Recurrence; repaired; restenosis; Safety; Sheep; Site; Stenosis; Stents; success; Surface; Surgeon; Surgical sutures; Techniques; Technology; Testing; Texas; Thrombosis; Time; Trauma; uptake; Vascular Graft; Ventricular