Pre-mature and critically ill infants often require frequent medication and nutrient administration, necessitating use of peripheral intravenous catheters for prolonged periods. Due to the small diameter of these newborns'veins, these catheters demonstrate a propensity for clotting, limiting their use and potentially endangering the health of these infants. We plan to develop an ultra-small diameter catheter for this critical application that will greatly improve outcomes. We have successfully developed a small diameter vascular graft using our hemo- compatible, non-clotting, and non-thrombogenic, elastin-collagen material (ECM) through our patented and patent pending novel process and incorporation of heparin. Our 3.75 mm arterial-mimetic graft, VasoGraft"""""""", allows blood to flow through it without blood clotting or thrombosis in tests lasting over 6 months. VasoGraft has been the topic of a currently funded NHLBI project (HL072670) for the past 4+ years with demonstrated patency in over 40 subjects tested in a porcine severed femoral artery end-to-end anastomosis model (artery to graft to artery reattachment), out to 200+ days, at the VA Med Ctr, Minneapolis, MN. Since ECM technology is a thermoplastic it can be molded to create ultra-small diameter constructs for use as catheters for long-term implantation. This application seeks funding through the two-year SBIR PHASE 1 grant to generate proof-of- concept studies, with the ultimate goal of developing catheters of sufficiently small diameter (d1mm) for long- term (e 2 weeks) use in newborns, where these catheters remain patent. We will leverage an existing, productive collaboration with MP&E, Inc, an engineering company with extensive experience producing catheters and other tubing medical devices and continue to collaborate with the VA Medical Center. Through these collaborations, ultra-small diameter constructs will be manufactured utilizing embedded reinforcements such as coiled or otherwise shaped tube reinforcement wire, to provide both flexibility and strength, while maintaining hemocompatibility. This ECM material creates an elastic wall structure to the catheter tube that is an insoluble, non-clotting, biocompatible surface to provide its proven non-thrombogenic, hemocompatibility.
The specific aims for this project are to: 1) Fabricate and manufacture Gel-Del catheter tubing of the appropriate diameter (21-24 gauge, e.g., d1 mm);2) Test the constructs in vitro for mechanical strength, integrity and consistency using standard catheter bench testing, anti-clotting analyses (standard Lee-White test and surface blood contact tests), and microscopic analyses (light and scanning electron microscopy);and 3) utilize in vivo models of indwelling catheters in a rat model to assess patency for two weeks or longer. We will also plan to assess this catheter's ability to fight infection due to its ability to allow tissue closure around the catheter surface. Future development will include anti-infection agents into the catheter ECM material for long- term drug delivery.
These aims will provide the proof-of-concept studies to allow the extension of our existing small diameter vascular graft technology into development of ultra-small catheter products for use in newborns.
The use of peripherally inserted percutaneous central venous catheters (PCVC) is important for providing both medication and nutrition in premature or critically ill infants. However, the materials used to make catheters can present problems associated with both hemocompatibility and infection complications, which limits their use and threatens the treatment of this patient population. The development of a neonatal catheter that uses our non-clotting elastin-collagen material (ECM) technology will greatly reduce the risks of such complications and greatly improve the treatment of critically ill newborns.
