0142-9612(95)00245-6 Biomoteriak 17 (1996) 1635-1642 0 1996 Elsevier Science Limited Printed in Great Britain. All rights reserved 0142-9612/96/$15.00 Selecting valid in vitro biocompatibility tests that predict the in tivo healing response of synthetic vascular prostheses* Yves Marois, Robert Guidoin, Raynald Roy, Tamas Vidovsky, Barbara Jakubiec, Marie-Frarqoise Sigot-Luizard+, Julian Braybrook$, Yahye Mehris , Ga&m Laroche and Martin King Departments Of Surgery, Pathology and Medecine, Lava/ University, Quebec Biomaterials Institute, St. Fran,cois d’Assise Hospital, Rheumatology and Immunology Research Centre, CHUL, Quebec City, Quebec GlK 7p4, Canada; +Dkpartement de GEnie Biologique, lJniversit6 de Technologie de CompiBgne, Compiggne, France; $Materiak Technology Group, European Business Liaison Officer, Laboratory of the Government Chemist, Teddington, Middlesex, TWll OLY, UK; §/nstitut de Cardiologie de Montrbal, Montrkal, QuBbec, Canada We have investigated the usefulness of six in vitro biocompatibility tests in predicting the healing performance of polyester vascular prostheses as observed in previous canine in vivo trials. Vascular grafts were evaluated by using (i) a direct contact (DC) assay, (ii) an extract dilution (ED) assay on murine fibroblast cells, (iii) a DC assay on endothelial cells, (iv) a complement activation study, (v) a leucocyte activation study of CD18 integrin subunit expression on human polymorphonuclear cells (PMNs) and (vi) interleukin-2 receptor expression on lymphocytes. Uncleaned polyester grafts had previously been associated with poor healing and gelatin-impregnated polyester grafts with delayed but satisfactory healing, whereas commercially cleaned polyester grafts had demonstrated excellent healing. Lightweight and heavyweight knitted and woven polyester grafts supplied specifically for this project were studied, each with a different surface condition, i.e. commercially available (CP), uncleaned (UP) and impregnated with gelatin (GP). The UP grafts induced fibroblast cytotoxicity according to the ED assay, poor migration and viability of endothelial cells, and an elevated expres- sion of CD18 and interleukin-2 receptor on PMNs and lymphocytes, respectively. In contrast, the CP grafts promoted good endothelial cell growth, no evidence of cytotoxicity and a weaker cell activation, and the GP grafts were found to be non-cytotoxic, to exhibit a good cellular response and to moderate cell activation. The complement activation assay and the DC assay on fibroblasts were found to be less useful and less discriminating. From this, it is concluded that the two cell activation measure- ments, the DC assay on endothelial cells and ED assay on fibroblasts, are useful in predicting the in vivo healing response of arterial polyester substitutes. 0 1998 Elsevier Science Limited Keywords: Biocompatibility, vascular prostheses, cell culture, endothelial cells Received 8 February 1995; accepted 30 June 1995 The increasing number of synthetic materials that are being introduced into the field of medicine means that there is an increasing demand for more discriminating tools to evaluate their safety and efficacy. Any adverse reaction by the host tissue to a biomaterial will probably result in failure. Consequently, the need for standardized methods and protocols for assessing the *This paper was presented at the 29th Congress of the European Society for Surgical Research, 16-19 May 1994, Montpellier, France. Correspondence to Dr R. Guidoin, Laboratory of Experimental Surgery, Room 1701 Services Building, Lava1 University, Quebec City, GlK 7P4, Canada. biocompatibility of materials has never been greater. At present, a variety of different types of cell culture methods are frequently used. They involve in vitro studies which may assess the cytotoxicity of different types of cells in terms of their morphology, adhesion and viability by either a direct or indirect contact assay, or by adding a diluted extract from the biomaterial to the culture medium. Other types of tests determine various cell functions, such as cell membrane integrity, replication, phagocytosis, the production of reactive oxygen species, secretion, activation chemotaxis and chemokinesis’. In spite of this plethora of possible test methods, the protocols currently required by North American and European 1835 Biomaterials 1996, Vol. 17 No. 19