Highly performing small-diameter polyurethane vascular grafts

Background of the project: There is a growing consensus among vascular surgeons about the need of reliable small-diameter-vascular grafts (SDVG) which could be taken from the shelf and used with a good degree of acceptability in any low diameter vessel replacement. This is related to the scarce availability of autologous prostheses (saphenous vein and mammary artery), the generally unsatisfactory condition of such material, and to the absence on the market of reliable smalldiameter synthetics. Up to now nor synthetic, neither biological, vascular grafts were able to be similar to the "ideal" vascular graft. The artificial vascular graft fabricated with mechanically resistant synthetic materials, such as expanded polytetrafluoroethylene (ePTFE) and polyethylene-terephthalate (Dacron ®), are up to now the most frequently used thanks to their good ability as large diameter vascular graft, for example for the substitution of the abdominal aorta where the diameters are about 10 mm; however, for smaller diameter substitutions the long term patency is not satisfactory. For the substitution of vessels below 6.0 mm in internal diameter no options are available to day and, therefore, the principal application of a reliable SDVG would be in the peripheral district, e.g.: below the knee, and at the cardiac level, e.g.: coronary artery bypass. Objective of the project: The general objective of a project such as the HYPER-GRAFT would be to produce less than 6.0 mm internal diameter artificial vessels to replace autologous blood vessels in humans. The specific and more realistic project objective is to prove with animal implantation experiments that the artificial graft prototypes developed within the project are at least comparable with autologous vessels. Scientific purpose: From a scientific point of view the main purpose of the HYPER-GRAFT project is to investigate fundamental issues related to the design and fabrication of a new generation of polyurethane small-diameter vascular grafts capable of elastically withstanding blood pressure, to be self-sealing, to remain patent in a low flow configuration, and not induce neointimal hyperplasia in the anastomotic regions. The grafts should promote a minimal tissue connective growth on the luminal surface and support the formation of a thin and stable "neointima", and last but not least to be "biostable" in long term implantation situations. The Consortium (updated): The HYPER-GRAFT consortium was originally composed of five specialized partners each of them having specific expertises. The development of the basis "spray-phase, inversion" graft fabrication technology was started by the partner Kontron Instruments S.p.A., Milano, Italy (KONTRON). KONTRON, which, besides having the role of project Coordinator, was also responsible for the following Tasks and/or Sub-tasks: Task 1 - Basic materials, Sub-task 1.3 - Validation of the sterilization method; Task 4 - Structural evaluation, Sub-task 4.1 - Characterization of prostheses mechanical properties; Task 5 - Prostheses design and fabrication. Unfortunately KONTRON, following bankruptcy, withdrew from the project before the beginning of the 3rd year. The partner Istituto di Fisiologia Clinica del CNR, Pisa, Italy (IFC-CNR) was an associated partner, originally in charge of the following Tasks and/or Sub-tasks: Task 3 - Material processing; Task 4 - Structural evaluation, Sub-task 4.2 - Characterization of prosthesis morphology; Task 6 - Animal pre-clinical evaluation, Sub-task 6.2 - Animal implantation site 2 - Pisa. IFC-CRN, following the withdrawal of KONTRON and upon approval of the European Commission, took over the role of project Co-ordinator and became also responsible for the work to be performed by KONTRON (Task 1 - Sub-task 1.3, Task 4 and 5), (Supplementary Agreement N° 001) The partner Cooperative Research Centre for Cardiac Technology, Sydney, Australia (CRC-CT) was an associated partner initially involved in the project in the following Tasks and /or Sub-tasks: Task 1 - Basic material, Sub-task 1.2 - Synthesis and characterization of new polymer material. CRC-CT was supposed to provide the HYPER-GRAFT consortium with a new elastomeric material based on silicone, developed in their laboratories. However CRC-CT, since it was not a EU member state, could participate in the project only as a non-financed partner, having the financial resources to be provided by the Australian Government. However, the Australian Government, for some reasons, did not provide the financial resources to CRCCT and, therefore, the Australian partner, after having provided some initial material, took the decision to quit from the project. The Cardio Vascular Surgery Service of Hopital Broussais, Paris, France (BROUSSAIS), is an associated partner which has been involved in the project from the beginning as responsible for the following Tasks and/or Sub-tasks: Task 6 - Animal pre-clinical evaluation Sub-task 6.2 - Animal implantation site 1 - Paris. The University of Liverpool, UK (LIVERPOOL), is an associated partner which has been involved in the project from the beginning as responsible for the following Tasks and/or Subtasks: Task 1 - Basic material, Sub-task 1.1 - Selection and characterization of basic materials; Task 2 - Biological evaluation, Sub-task 2.1 - In vitro and in vivo evaluation of biocompatibility, Sub-task 2.2 - In vitro and in vivo evaluation of biostability; Task 6 - Animal pre-clinical evaluation, Sub-task 6.3 - Post-implant morphological evaluation. In addition LIVERPOOL performed some work that should have been done by KONTRON in the following Task and Sub-task: Task 4 - Structural evaluation, Sub-task 4.1 - Characterization of prostheses mechanical properties. Finally, the HYPER-GRAFT project was carried on only by IFC-CNR, BROUSSAIS and LIVERPOOL. Project outcomes: In terms of in vivo graft patency the outcome of the HYPER-GRAFT project was not satisfactory, both in the sheep and in the pig model, and did not met the originally proposed measurable medical objective. This was probably due from one side to the non complete suitability of the materials available on the market for the fabrication of a critical device such a small-diameter vascular graft. On the other side it has been recognised that there was a lack of information about the ideal structure the graft should posses in order to prevent early phenomena of thrombosis and to provide long-term patency. In this area more investigation and understanding will certainly be necessary. Based on these outcomes the sheep implantation experiments at BROUSSAIS and the pig implantation experiments at IFC-CNR were suspended since it was recognized that a more understanding about the optimal material/graft structure would have been necessary in order to design better grafts prototypes. However, even if the grafts patency results were not satisfactory, the information gained in term of surgical feasibility of the implanting technique (easy of handling, pliability, easy of suturing, suture retention, etc.) and in term of material/graft structure relationship (mechanical behaviours, compliance, wall blood infiltration, wall bleeding, etc.) are of high scientific value and will be useful and applicable to design new biomaterial and/or graft structure with improved performance to be used for future implantation experiments.