title: In vitro and in vivo evaluation of blood coagulation activation of polyvinyl alcohol hydrogel plus dextran-based vascular grafts.
abstract: Polyvinyl alcohol hydrogel (PVA) is a water-soluble synthetic polymer that is commonly used in biomedical applications including vascular grafting. It was argued that the copolymerization of PVA with dextran (Dx) can result in improvement of blood-biomaterial interactions. The focus of this experimental study was to assess that interaction through an in vivo and in vitro evaluation of the coagulation system activation. The thrombogenicity of the copolymer was determined by quantification of platelet adhesion through the lactate dehydrogenase assay, determination of whole blood clotting time, and by quantification of platelet activation by flow cytometry. The thrombin-antithrombin complex blood levels were also determined. The obtained results for the in vitro assays suggested a non-thrombogenic profile for PVA/Dx. Additionally in vivo coagulation and hematological parameters were determined in an animal model after PVA/Dx vascular graft implantation. For coagulation homeostasis assessment, the intrinsic and extrinsic pathway's activation was determined by measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT). Other markers of coagulation and inflammation activation including d-dimers, interleukin-6, and C-reactive protein were also assessed. The PVA/Dx copolymer tended to inhibit platelet adhesion/activation process and the contact activation process for coagulation. These results were also confirmed with the in vivo experiments where the measurements for APTT, interleukin-6, and C-reactive protein parameters were normal considering the species normal range of values. The response to those events is an indicator of the in vitro and in vivo hemocompatibility of PVA/Dx and it allows us to select this biomaterial for further preclinical trials in vascular reconstruction.
authors.affiliation: Departamento de Zootecnia, Universidade de Évora, Pólo da Mitra, Apartado 94, 7002-554, Évora, Portugal; Instituto de Ciências Agro-ambientais Mediterrânicas (ICAAM), Pólo da Mitra, Apartado 94, 7002-554, Évora, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Alexandre
authors.forename: Elísio
authors.initials: E
authors.lastname: Costa
authors.forename: Susana
authors.initials: S
authors.lastname: Coimbra
authors.forename: Alice
authors.initials: A
authors.lastname: Silva
authors.forename: Ascensão
authors.initials: A
authors.lastname: Lopes
authors.forename: Miguel
authors.initials: M
authors.lastname: Rodrigues
authors.forename: Marta
authors.initials: M
authors.lastname: Santos
authors.forename: Ana Colette
authors.initials: AC
authors.lastname: Maurício
authors.forename: José Domingos
authors.initials: JD
authors.lastname: Santos
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Luís
mesh_terms: D000328:Adult; D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure; D001807:Blood Vessel Prosthesis; D003911:Dextrans / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010447:Peptide Hydrolases / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects; D011126:Polypropylenes / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000494:pharmacology*; D012756:Sheep; D014914:Whole Blood Coagulation Time
chemical_list: D003911:Dextrans; D011126:Polypropylenes; C046193:antithrombin III-protease complex; C062364:polyvinyl alcohol hydrogel; D000990:Antithrombin III; D011142:Polyvinyl Alcohol; D010447:Peptide Hydrolases
keywords: coagulation; dextran; homeostasis; polyvinyl alcohol hydrogel; vascular graft