Drug Eluting Peri-vascular Sleeve

It is estimated that over 800,000 small diameter synthetic vascular grafts are implanted worldwide each year. There are two main applications for vascular grafts; vascular reconstruction in patients with peripheral vascular disease and the construction of specialised arterio-venous access conduits for patients with end stage renal disease who require haemodialysis. Within both of these vascular graft patient populations there is an important clinical problem related to and as yet unresolved failure of synthetic vascular grafts. In both applications the insertion of a synthetic graft tube to function as a vascular conduit initiates a process of increased smooth muscle cell division (proliferation) at the anastamotic junction of the implanted vascular graft. This process referred to as a vasculo-proliferative response or neointimal hyperplasia, results from smooth muscle cell proliferation and migration from media to intima and results in the narrowing of the lumen of the vessel. This narrowing or stenosis, in turn, leads to a reduction of blood flow through the graft and significantly increases the propensity of the graft to clot and thereby fail. In an initial "Proof of Principle" study, we demonstrated the feasibility of delivering rapamycin using a perivascular source for preventing reducing neointimal hyperplasia at the venous anastamotic end of a PTFE graft. The components for drug delivery used in that study consisted of a biocompatible, biodegradable matrix (Type 1 Bovine Collagen) and 250 micrograms of Rapamycin. In this study, the collagen matrix was saturated with the rapamycin in the surgical suite a short time prior to perivascular delivery. The primary aim of this Phase 1 submission, will be the development of the next generation (as opposed to the "early generation prototype that was used in the "Proof of Principle" study) rapamycin eluting collagen matrix sleeve. Following fabrication of the device prototypes, in vitro tests for device characterization and an in vivo feasibility study using a sheep A-V Graft model will be performed. The results of the Phase 1 study will help define the specifications for rigorously controlled production of the device that will be used in the phase 2 pre clinical followed by a feasibility human study. If the rapamycin eluting collagen sleeve is found to be effective it has the potential to have a major impact on patient care and the allocation of health care dollars.