Bird, Richard le Roy; (1992) Reduction of prosthetic vascular graft thrombogenicity by phosphorylcholine containing lipids and polymers. The thrombogenicity of arterial grafts can be modified by coating with new polymers that mimic haemocompatible blood cell membranes. Masters thesis (M.S), UCL (University College London).

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Abstract

This thesis reviews the clinical problems associated with atheromatous arterial disease, its treatment with prosthetic bypass biomaterials, and considers the development and assessment of these materials. The thesis tests the hypothesis that coating existing biomaterials with biological membrane phospholipids, which mimic the good haemocompatibility of erythrocyte membranes, may be a step towards the solution of the problem of biomaterial thrombogenicity. Twelve phospholipids from the RBC membrane are evaluated as haemocompatible surface coatings by two in vitro assays; 1) material thrombelastography (MTEG), and 2) fibrinopeptide A generation. The technique of MTEG is presented in detail and important developments of this methodology are described. The underlying mechanisms of haemocompatibility of these phospholipids are examined by incubation of lipid liposomes with human plasma using individual clotting factor assays. Phospholipids and polymers containing phosphorylcholine (PC), namely sphingomyelin and dipalmitoylphosphatidylcholine (DPPC), very significantly reduce the activation of platelets and clotting factors. They are considerably better than the biomaterials Dacron and PTFE. The stability of DPPC, sphingomyelin and the PC-polymers during sterilisation with steam, ethylene oxide and irradiation are studied. Marked decomposition is documented using the techniques of chromatography, FTIR and MTEG. Despite radiation induced changes, sphingomyelin and some PC-polymers remain less thrombogenic than PTFE or Dacron to both platelets and clotting factors. Untreated Dacron vascular grafts are compared with grafts coated with sphingomyelin and two PC-polymers in a double blind randomised in vivo trial, using a modified sheep arteriovenous fistula preparation. The end points are indium-111 platelet imaging and uptake, platelet survival times, iodine-125 fibrinogen uptake and graft histology. Sphingomyelin significantly reduces platelet uptake by 66% and the cross sectional area of graft thrombus by 90% compared to the control grafts. All three materials prolong platelet survival, but do not reduce fibrinogen activation significantly. The original hypothesis is supported and further investigation of these materials should be undertaken.

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