The long term objective is the development of a generalized treatment to improve the blood compatibility of medical polymers. The method takes advantage of the high affinity of serum albumin for aliphatic chains grafted to polymer backbones. The hypothesis underlying this approach is that a continuous layer of the patient's serum albumin can be rapidly adsorbed from plasma and block the adsorption and contact-activation of other plasma proteins, which trigger various host defenses (coagulation, platelet aggregation, leukocyte activation, complement activation, activation of the plasminogen system). In theory, the albumin layer can be renewed by continuous exchange with albumin in plasma. The technique is applicable to oxygenators, dialyzers, artificial hearts, chemical sensors, catheters, vascular grafts, and other devices, without altering their performance.
The specific aims of this proposal are focused on in vitro and in vivo evaluations of the technique. Two polymers, BiomerR and DacronR will be derivatized with alkyl sidechains chosen to optimize albumin affinity. The albumin affinity (albumin layer density and homogeneity) will be measured and related to alkyl yield. Environmental influences will be evaluated including: fluid shear rate, time, albumin and serum proteins implicated in thrombosis (fibrinogen, vonWillebrand factor and high molecular weight kininogen). The initial uniformity and retention of the albumin layer, and its potential for renewal will thus be evaluated. A prediction of the in vivo retention of albumin will be made from these results, employing a first order reaction kinetics model. Coagulation and leukocyte function studies are proposed for a first order evaluation, in vitro, of host response. The in vivo response of albumin and platelets in a canine model to optimally alkylated arterial catheters and grafts will be investigated, employing three models: bilaterally implanted Biomer catheters, bilaterally implanted ileo-femoral woven Dacron grafts and the aortic Dacron prosthesis. Albumin adsorption and retention, platelet adhesion on implanted surfaces and bulk platelet survival and serotonin release will be used to evaluate material performance. Histological analysis of excised catheters and grafts will complement these data. The in vivo investigations of specific mechanisms will be compared with the in vivo results. The results of this analysis include: characterization of the efficacy of this method and an evaluation of the inhibition of specific surface contact activation mechanisms in which the cited plasma proteins and cells are implicated.
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