In vitroandin vivoevaluation 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.

Smooth muscle tissue engineering in crosslinked electrospun gelatin scaffolds

“…1 Given the thrombogenicity of vascular grafts made from synthetic polymers, 2,3 the development of tissue engineered vascular grafts based on natural biopolymers has been researched intensively. [4][5][6] Such biopolymers have been considered as coatings, mixture component, comingled, or chemically linked with synthetic polymers [7][8][9][10][11] or in a single natural biopolymer-based scaffold. [12][13][14][15] Such natural biopolymers considered for vascular grafts are collagen, gelatin, elastin, and fibrin.…”

Comparison of catheter thrombogenicity in a modified chandler loop model using goat blood

“…Animal models are routinely used to evaluate the safety and efficacy of new medical devices, including central catheters and other devices used in the vascular environment. Published reports have commonly used small livestock species, such as sheep or goats, for in vivo hemocompatibility testing of intravascular devices and materials . The use of animals as a source of blood for in vitro hemocompatibility testing systems is a natural extension of using animals in preclinical testing.…”

“…Published reports have commonly used small livestock species, such as sheep or goats, for in vivo hemocompatibility testing of intravascular devices and materials. 4,5,[10][11][12] The use of animals as a source of blood for in vitro hemocompatibility testing systems is a natural extension of using animals in preclinical testing. The potential for low-cost sample collection and ease of sample access can make small livestock ideal candidates to provide blood samples for thrombogenicity testing.…”

Adhesion and activation of platelets from subjects with coronary artery disease and apparently healthy individuals on biomaterials

“…For long‐term patency of vascular grafts, it is vital to prevent undesirable protein and platelet adhesion. However, despite the widespread testing and use of cardiovascular implants, there is still a lack of fundamental understanding of the very complex and interlinked reactions that occur when an artificial material is exposed to blood …”

“…However, despite the widespread testing and use of cardiovascular implants, there is still a lack of fundamental understanding of the very complex and interlinked reactions that occur when an artificial material is exposed to blood. [12][13][14] In addition to choosing insufficiently suitable polymers that may cause implant failure, also in vitro hemocompatibility tests are discussed to be inadequate in predicting the performance of cardiovascular implants in vivo. 15,16 Tests Correspondence to: F. Jung; e-mail: friedrich.jung@hzg.de are carried out worldwide but a generally accepted standardization regarding pre-analytical handling of the blood, test conditions, test parameters, static or dynamic conditions, flow conditions, and last but not least, which type of cells and donors should be included is lacking.…”