Edward W. Merrill

Gamma sterilization of UHMWPE articular implants: an analysis of the oxidation problem

Gamma irradiation of Ultrahigh Molecular Weight Polyethylene (UHMWPE) leads to long-lived free radicals which react with oxygen. Diffusion of oxygen, occurring over months or years, controlled by the permeability characteristics of the polymer, results in progressive oxidation, breaking of polymer chains, alteration of the crystalline portion of the polymer, and deterioration of the mechanical properties of the polymer. This paper reviews the observations in the literature on this issue and then presents a conceptual model concerning the interplay of radical diffusion, oxygen diffusion, non-uniform permeability, and free-radically driven chain reactions in order to explain these observations. The suggested model is based on literature that is available on the oxidation of linear polyethylenes during and after irradiation. The model directs the attention of researchers in the field of orthopaedic implants to the complexity of the process and the variety of issues and parameters to be considered while studying the long-term effects of radiation sterilization on UHMWPE.

Non-Newtonian Rheology of Human Blood - Effect of Fibrinogen Deduced by "Subtraction"

A study of the rheological properties of human blood, from donors in normal health, was carried out by means of a coaxial cylinder viscometer designed to measure very small levels of stress under conditions of “creeping” flow. It was found that under these conditions of measurement the rheological properties could be conveniently presented by plotting the square root of shear stress against square root of shear rate. For normal blood, a nearly linear relation is found on such a plot, and the intercept on the stress axis at zero shear rate represents the square root of yield stress, separate determination of which is made by other means. Similar plots for (i) defibrinated blood and (ii) suspensions of red cells in isotonic saline solution reveal no yield stress. Thus it is concluded that fibrinogen is essential for the existence of yield stress in human blood. Furthermore, the approximate linearity, for normal blood, of the square root of shear stress with square root of shear rate, and the yield stress intercept, are of great interest inasmuch as mathematically identical relations ensue according to an equation developed by Casson based on a physical model in which the elementary particles of a suspension are capable of reversible association into rod-like structures, the length of which is controlled by the shear rate. It is of interest to consider the Casson model in the light of rouleaux formation and the relation of fibrinogen to rouleaux formation.

Molecular rearrangements in ultra high molecular weight polyethylene after irradiation and long-term storage in air

Abstract Molecular rearrangements and alterations in supermolecular structure of ultra high molecular weight polyethylene (UHMWPE) due to cross-linking and oxidation-induced chain scission following irradiation and subsequent storage in air at room temperature have been studied over a period of 29 months. The techniques that were used are: equilibrium swelling in decalin, differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), Fourier transform infrared spectroscopy (FTIR) and electron spin resonance (ESR). The experimental results indicate that immediately after irradiation, cross-linking and an increase in crystallinity are the important processes. With time, chain scission induced by oxidation takes place resulting in a new phase of thinner crystallites in the amorphous region. In the absence of oxygen diffusion limitations, the free radicals survive for 30 months in the form of peroxides. The effect produced by higher doses and shorter aging times correspond to those produced by lower doses and longer aging times, thus, suggesting a superposition law between dose and aging time.

SPECIAL ARTICLE Clinical Implications of Blood Rheology Studies

Blood viscosity is dependent on the shear rate at which it is measured. Reversible red cell aggregation is largely a function of fibrinogen-red cell interaction at normal hematocrits. Red cell aggregation is the basis for the anomalous rheological behavior of blood, since a considerable fraction of the shear stress applied to blood flowing at low shear rates is required to break up the aggregates accounting for the greater shear stress required to produce a given shear rate of low magnitude. Erythrocyte sedimentation rate is also a measure of red cell aggregation and has been used as an indicator of the “suspension stability” of blood. The tendency for red cell aggregation is greatest during periods of low flow states and is maximum when the blood is standing still. At such times, a certain shear stress, the yield stress, must be applied to overcome the reversible red cell-fibrinogen bond, causing the blood to “yield” or begin to flow. Manipulation of blood viscosity and yield shear stress, by hemodilution or fibrinogen dilution are readily accomplished, and experimental studies indicate that these rheological alterations have circulatory and metabolic significance.

SURFACE‐INDUCED PLATELET ADHESION, AGGREGATION, AND RELEASE*†

The secretion of intracellular constituents (“release reaction”) and aggregation are common responses to stimulation of platelets by a variety of agonists and together constitute the major aspects of what Holmsen has termed “the basic platelet reaction.” These processes comprise the ultimate expression of a complicated series of biochemical reactions that have been extensively studied in vitro and about which much is known. There is evidence that an early event is activation of an endogenous phospholipase leading to hydrolysis of phospholipids in the platelet membrane, thought principally to involve phosphatidyl choline, with liberation of arachidonic acid.”-‘ Enzymatic conversion of this essential fatty acid to labile endoperoxide precursors of the stable prostaglandins, PGE, and PGF,,, can be blocked by aspirin and other nonsteroidal anti-inflammatory agents, which are powerful inhibitors of the release reaction and platelet clumping.s--7 Samuelsson and associates have reported that prostaglandins are only a minor fraction of endoperoxide breakdown, quantitatively speaking, several orders of magnitude more of the endoperoxide molecules being converted to an unstable biologically active substance termed thromboxane This compound is postulated to be the principal effector in induction of the platelet release reaction, aggregation then resulting from the products of release. Prostaglandin E,, which does not itself initiate platelet activity, apparently has an important amplifying effect on processes induced by other stirnuli.l0~ The release reaction of platelets in response to most stimuli is accompanied by a fall in the platelet content of cyclic AMP (CAMP) . l z % Like prostaglandin synthesis, this effect is blocked by aspirin. There is much evidence to suggest that CAMP is important in the regulation of platelet activity, although the details of its role are disputed. For example, marked inhibition of platelet function results from an increase in platelet CAMP, which may be produced in plateletrich plasma by incubation with dibutyryl cAMP,I-’ by inhibition of platelet

Shear Rate Dependence of the Viscosity of Whole Blood and Plasma

The analysis of the shear stress/shear rate relationship, and thus the viscosity/shear rate relation, of blood and plasma shows that (i) freshly drawn whole blood has a large shear rate dependence on viscosity (viscosity falls as shear rate increases), and (ii) the shear rate dependence of viscosity of whole blood, or plasma, that has not been treated to prevent clotting is substantially greater than that of whole blood or plasma treated with anticoagulants. The influence of this phenomenon upon the fluid mechanics of the microcirculation is commented upon.

Poly(ethylene oxide) star molecules: synthesis, characterization, and applications in medicine and biology.

Festschrift remark-It was an honor to be invited to honor Allan Hoffman on the occasion of his 60th birthday. It seems like yesterday that Allan and I shared an office in old Building 12 on the M.I.T. campus. At that time Allan had lost a bout with a snow covered mountain while on skis, and consequently moved about awkwardly in our already small room on crutches with a heavy cast. Despite these impediments, he carried on his classroom activities with typical energy. It was even earlier that at M.I.T., under the supervision of Ed Gilliland and myself, he carried out his doctoral research on the radiation grafting of styrene to polyethylene. Both he and I have dabbled in radiation chemistry on and off since then-he far more than I. Neither of us at that epoch had much idea about biomaterials or medical applications of materials-at least I did not-perhaps Allan had it in the back of his mind. The University of Washington, Seattle, is recognized as one of the great centers of biomedical engineering in the wor...

Esca studies of polyurethanes: blood platelet activation in relation to surface composition

Abstract Segmented polyurethanes (SPU) were synthesized with polyethylene oxide (PEO), polypropylene oxide, or polytetramethylene oxide as the “soft segment,” from the respective polyether diols, of which molecular weight varied from 600 to 2000. The “hard segment” was created from ethylene diamine and tolylene diisocyanate or 4,4′-diphenylmethane diisocyanate. Platelet activation was assessed using columns packed with beads coated with each of the SPU by solutions from which the solvent was subsequently evaporated. Citrated whole human blood was passed through the columns and the platelet count in aliquots leaving the columns was compared with the platelet count in blood that had not contacted the column surface. By this method the fraction of platelets retained in the column averaged for several donors, ρ, was determined. In parallel experiments, SPU surfaces formed under identical conditions by evaporation of solvent were examined by X-ray electron spectroscopy for carbon, oxygen, and nitrogen content of the surface. The carbon C1s spectra proved to be particularly useful, when analyzed for the components with peaks respectively at 286 eV (carbon not bonded to an ether oxygen) and at 288 eV (carbon bonded to an ether oxygen). The platelet retention index ρ was found to increase nearly linearly with the ratio of the 286-eV intensity to the 288-eV intensity, and extrapolated to nearly zero for zero value of the intensity ratio, which would correspond to amorphous PEO, suggesting that if a surface were only amorphous PEO it would be remarkably inactive toward platelets. In contrast, nitrogen spectra show no systematic relationship with ρ.

Hepatocyte culture on carbohydrate-modified star polyethylene oxide hydrogels

We describe the synthesis and in vitro biological characterization of a new class of carbohydrate-modified hydrogels based on radiation-cross-linked star polyethylene oxide (PEO). Hydrogels were synthesized from either of two types of PEO star molecules in order to vary the terminal hydroxyl content of the gels while keeping other gel properties such as molecular weight between cross-links and water content constant. The resulting gels were covalently modified with monosaccharide ligands and the behaviour of primary rat hepatocytes on the modified gels was evaluated under culture conditions. Hepatocytes exhibited a sugar-specific adhesion to the modified gels, adhering to gels bearing galactose but not glucose. Cell spreading was observed on both types of galactose-modified PEO star gels; moreover, the gels supported long-term (6 d) culture and differentiated function of primary hepatocytes. Further, on comparing the cell spreading behaviour observed on the PEO star gels with that reported previously for galactose-modified polyacrylamide, we find that our gels elicit spreading at ligand concentrations lower by an order of magnitude. A simple mechanistic analysis indicates that this enhanced ability of PEO star gels to support spreading of primary hepatocytes on low concentrations of immobilized galactose derives from freedom of the immobilized ligands to come within sufficiently close proximity to mimic a high-affinity branched oligosaccharide.

Gradient crosslinking of UHMWPE using irradiation in molten state for total joint arthroplasty

Increased crosslink density increases the wear resistance of ultra-high molecular weight polyethylene (UHMWPE) acetabular components used in total hip reconstructions. However, increasing crosslink density can reduce the mechanical properties of UHMWPE. Other researchers have tried to limit the crosslinking to a superficial layer on the articulating surfaces to retain the properties of the virgin polymer. We present here a method of producing a gradient of crosslink density across the acetabular component. Acetabular liners with 26 mm inner diameter were machined from the UHMWPE. The liners were then irradiated at 140 degrees C in the molten state of the polymer using a 2 MeV electron beam with limited penetration of the effects of radiation into polyethylene. The liners were then machined to an inner diameter of 32 mm to remove the radiation induced oxidized surface layer. The limited penetration of the e-beam resulted in a gradient of crosslink density with a crosslink density of 0.15 +/- 0.01 mol/dm3 near the articulating surfaces and 0.12 +/- 0.01 mol/dm3 near the backside. The concentration of the trans-vinylene unsaturations decreased gradually as a function of depth from the articulating surfaces to the backside of the liners. The wear resistance of the melt-irradiated liners was contrasted with those of conventional liners using the Boston hip simulator. The gravimetric wear rate was 27 +/- 5 mg million cycles with the conventional liners, while the melt-irradiated acetabular liners did not show any weight loss.