Small diameter arterial vascular substitutes for emergency surgery – SUVARU

While it is now possible to replace all or part of an artery with an internal diameter greater than 6 mm with a prosthesis, there is no clinical solution for arteries with a smaller diameter. Autologous grafting is then the only solution. In an emergency traumatic situation, in an operating theatre or at the site of a disaster, autologous grafting is not feasible and the surgeon has no reliable temporary solution. The main objective of the project is to develop a set of temporary small-diameter prostheses in the form of a "vascular kit" for immediate use to replace a damaged artery while it is being replaced by an autograft. The technological, biological, mechanical and clinical issues for the design of these prostheses are simplified compared to the design of long-term vascular substitutes, but nevertheless constitute a set of significant challenges to be met. Polyvinyl alcohol (PVA) tubes with small internal diameter are prepared by physical crosslinking of aqueous solutions of polyvinyl alcohol (PVA) placed in suitable molds. Grafting of their luminal surface with low molecular weight heparin has made it possible to prepare prostheses that do not present hemolysis and do not induce platelet aggregation in vitro, with for the first time obtaining compliance in the range of human arterial compliances. In vitro hemocompatibility is satisfactory and some preliminary results of in vivo evaluation in a murine model are encouraging. These prostheses must be optimized for internal diameters up to 4 mm before proceeding to an in vivo evaluation in a ovine model. With the aim of achieving optimal efficacy of the prostheses over a period of 7 days, the objectives of SUVARU are therefore as follows:
1) Preparation of PVA tubes up to 4 mm internal diameter with several luminal heparin contents to improve their hemocompatibility.
2) Evaluation and optimization of hemocompatibility in human whole blood and cytocompatibility with human vascular cells, in particular with platelets in static and flow conditions.
3) Evaluation of mechanical properties in static and pulsatile flow conditions.
4) Adaptation to prostheses of a clinical sutureless anastomosis system compatible with emergency implantation.
5) Sterilization of formulations and validation of mechanical and biological properties.
6) Evaluation of biocompatibility in an ectopic site in a rat model.
Go-no go: Project termination if no formulation is satisfactory.
7) Evaluation of 1 to 3 formulations of internal diameter adapted to the rat abdominal aorta replacement model with MRI monitoring of permeability up to 7 days of implantation, and histological and mechanical analyses of the explants.
8) A selected formulation will be evaluated over the same period in a ovine model of peripheral vascular replacement with a 4mm internal diameter tube and implanted using an adapted anastomotic system.
The SUVARU project benefits from a highly complementary multidisciplinary consortium: the Bordeaux Center for Clinical Investigation and Technological Innovations (Inserm CIC1401/CHU de Bordeaux), the Materials Center, MINES Paristech (CNRS UMR 7633), and the Army Biomedical Research Institute, under the coordination of the Translational Vascular Research Laboratory (Inserm U1148).