In vitro and in vivo hemocompatibility evaluation of a new dermatan sulfate-modified PET patch for vascular repair surgery Manel Dhahri, 1 * Violeta Rodriguez-Ruiz, 2 * † Rachida Aid-Launais, 2 V eronique Ollivier, 2 Graciela Pavon-Djavid, 2 Cl  ement Journ e, 2 Liliane Louedec, 2 Fr ed eric Chaubet, 2 Didier Letourneur, 2 Raoui M. Maaroufi, 3 Anne Meddahi-Pell e 2 * 1 Laboratoire de Pharmacologie 04/UR/01-09, Facult e de M edecine, Universit e de Monastir, Monastir, Tunisia 2 INSERM, U1148, LVTS, Universit e Paris 13, Universit e Paris Diderot, Sorbonne Paris Cit e, Paris, France 3 Institut Sup erieur de Biotechnologie de Monastir, Laboratoire de recherche G en etique, biodiversit e et valorisation des bioressources LR11ES41, Universit e de Monastir, Monastir, Tunisia Received 13 November 2015; revised 27 May 2016; accepted 1 June 2016 Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33733 Abstract: The development of new vascular devices requires to study the effects of materials on blood cells and on coagu- lation, both in vitro and in vivo. In this study, we have devel- oped a new material by grafting dermatan sulfate (DS) from shark skin onto polyethylene terephthalate (PET). We have evaluated the haemocompatibility of PET-DS material in vitro by measuring thrombin generation, plasma recalcification time, hemolytic activity, and platelet adhesion and in vivo with a model of vascular patch in rat abdominal aorta. In vitro, our results have shown that PET-DS is a nonhemolytic material, able to inhibit thrombin generation and platelet adhesion. In vivo studies by Doppler echographic evaluation 20 days after implantation have shown that the PET-DS patch was integrated in the vessel wall and covered by a layer of cells. In conclusion, PET-DS has good haemocompatibility properties and could be a promising tool for vascular sur- gery. V C 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000–000, 2016. Key Words: polyethylene terephthalate (PET), dermatan sul- fate, immobilization, material testing, haemocompatibility, vascular patch, in vitro, in vivo How to cite this article: Dhahri M, Rodriguez-Ruiz V, Aid-Launais R, Ollivier V, Pavon-Djavid G, Journ e C, Louedec L, Chaubet F, Letourneur D, Maaroufi RM, Meddahi-Pell e A. 2016. In vitro and in vivo hemocompatibility evaluation of a new dermatan sulfate-modified PET patch for vascular repair surgery. J Biomed Mater Res Part B 2016:00B:000–000. INTRODUCTION Polyethylene terephthalate (PET) is one of the most impor- tant polymeric materials used in the biomedical field because of its good mechanical properties and stability. 1–4 However, PET presents several limitations, mostly due to its synthetic origin, such as low blood-compatible properties 5 and moderate tissue inflammatory response. 6 There is, therefore, a clear need for developing new PET-based bio- materials with better hemocompatibility that will help avoiding the thrombosis risk at the site of injury. Indeed, thrombus formation is still one of the main issues affecting blood-contacting medical devices. 7 Activation of coagulation cascade occurs after contact of blood with a foreign sur- face 8,9 (contact activation pathway) or after exposition of tissue factor (TF) which is considered as the main initiator of coagulation and is expressed by mural cells 10 (extrinsic pathway of coagulation). Thrombin, the end-product of the cascade, in turn cleaves fibrinogen into fibrin that can accu- mulate on the biomaterial surface within minutes. Thus, the capacity of a biomaterial to trigger thrombin generation is important to consider when analyzing thrombogenicity. One strategy to increase the haemocompatibility of these devices could be the immobilization of sulfated-polysaccharides as antithrombotic agents at their surface. Heparin, has been com- monly integrated into biomaterials to prevent intrinsic thrombo- genicity. 11 However, heparin can cause thrombocytopenia (PF4) and some patients develop antibodies against heparin–PF4 complex resulting in both a loss of circulating platelets and a thrombotic state. 8,12–14 Due to these side effects, the search of alternatives is still necessary. Dermatan sulfate (DS), is an ubiq- uitous component of the extracellular matrix and is generally isolated from mammalian (bovine and porcine intestinal mucosa) 15 sources. In previous studies, we isolated and charac- terized a DS from the skin of the Scyliorhinus canicula shark, 16,17 a nonmammalian marine product, which decreases the risk of pathogenic contamination. 5,18,19 Furthermore, we demonstrated that soluble DS exhibited an antithrombin activity mediated by heparin cofactor II, a serine protease inhibitor. 17 We have also *These authors contributed equally to this work. † Present address: Universit e de Cergy Pontoise, ERRMECe, Biomaterials for Health group, I MAT, 95302 Cergy Pontoise, France Correspondence to: A. Meddahi-Pell e; INSERM, U1148, Laboratoire de Recherche Vasculaire Translationnelle, H^ opital Bichat, 46 rue H Huchard, Paris 75018, France. E-mail: anne.pelle@inserm.fr V C 2016 WILEY PERIODICALS, INC. 1