Cobalt Chromium Molybdenum Research Articles

Tribological performance of various CoCr microstructures in metal-on-metal bearings

Hip simulators have been used for ten years to determine the tribological performance of large-head metal-on-metal devices using traditional test conditions. However, the hip simulator protocols were originally developed to test metal-on-polyethylene devices. We have used patient activity data to develop a more physiologically relevant test protocol for metal-on-metal devices. This includes stop/start motion, a more appropriate walking frequency, and alternating kinetic and kinematic profiles. There has been considerable discussion about the effect of heat treatments on the wear of metal-on-metal cobalt chromium molybdenum (CoCrMo) devices. Clinical studies have shown a higher rate of wear, levels of metal ions and rates of failure for the heat-treated metal compared to the as-cast metal CoCrMo devices. However, hip simulator studies in vitro under traditional testing conditions have thus far not been able to demonstrate a difference between the wear performance of these implants. Using a physiologically relevant test protocol, we have shown that heat treatment of metal-on-metal CoCrMo devices adversely affects their wear performance and generates significantly higher wear rates and levels of metal ions than in as-cast metal implants.

Interpretation of electrochemical measurements made during micro-scale abrasion-corrosion

This paper brings together and analyzes recent work based on the interpretation of the electrochemical measurements made on a modified micro-abrasion-corrosion tester used in several research programmes. These programmes investigated the role of abradant size, test solution pH in abrasion-corrosion of biomaterials, the abrasion-corrosion performance of sintered and thermally sprayed tungsten carbide surfaces under downhole drilling environments and the abrasion-corrosion of UNS S32205 duplex stainless steel. Various abrasion tests were conducted under two-body grooving, three-body rolling and mixed grooving-rolling abrasion conditions, with and without abrasives, on cast F75 cobalt–chromium–molybdenum (CoCrMo) alloy in simulated body fluids, 2205 in chloride containing solutions as well as sprayed and sintered tungsten carbide surfaces in simulated downhole fluids. Pre- and post-test inspections based on optical and scanning electron microscopy analysis are used to help interpret the electrochemical response and current noise measurements made in situ during micro-abrasion-corrosion tests. The complex wear and corrosion mechanisms and their dependence on the microstructure and surface composition as a function of the pH, abrasive concentration, size and type are detailed and linked to the electrochemical signals. The electrochemical versus mechanical processes are plotted for different test parameters and this new approach is used to interpret tribo-corrosion test data to give greater insights into different tribo-corrosion systems. Thus new approaches to interpreting in-situ electrochemical responses to surfaces under different abrasive wear rates, different abrasives and liquid environments (pH and NaCl levels) are made. This representation is directly related to the mechano-electrochemical processes on the surface and avoids quantification of numerous synergistic, antagonistic and additive terms associated with repeat experiments.

Lubricity and stability of poly(2-methacryloyloxyethyl phosphorylcholine) polymer layer on Co–Cr–Mo surface for hemi-arthroplasty to prevent degeneration of articular cartilage

Migration of the artificial femoral head to the inside of the pelvis due to the degeneration of acetabular cartilage has emerged as a serious issue in resurfacing or bipolar hemi-arthroplasty. Surface modification of cobalt–chromium–molybdenum alloy (Co–Cr–Mo) is one of the promising means of improving lubrication for preventing the migration of the artificial femoral head. In this study, we systematically investigated the surface properties, such as lubricity, biocompatibility, and stability of the various modification layers formed on the Co–Cr–Mo with the biocompatible 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer by dip coating or grafting. The cartilage/poly(MPC) (PMPC)-grafted Co–Cr–Mo interface, which mimicked a natural joint, showed an extremely low friction coefficient of <0.01, as low as that of a natural cartilage interface. Moreover, the long-term stability in water was confirmed for the PMPC-grafted layer; no hydrolysis of the siloxane bond was observed throughout soaking in phosphate-buffered saline for 12 weeks. The PMPC-grafted Co–Cr–Mo femoral head for hemi-arthroplasty is a promising option for preserving acetabular cartilage and extending the duration before total hip arthroplasty.

A comparison of the effects of prosthetic and commercially pure metals on retrieved human fibroblasts: The role of surface elemental composition

The most common clinical cause of long-term failure in total joint replacement surgery is inflammatory aseptic osteolysis; a condition in which bone surrounding the prosthetic implant, and to which the implant is attached, is resorbed, rendering the artificial device loose and painful. Historically, the severity of this bone resorptive process has been thought to be predominately attributed to the size and shape of wear-debris particles, particularly the metallic particulates that interact biologically/immunologically with cells in the joint. Because the cytotoxic reactions are the result of interactions between the cells and the surfaces of the particulates, it is not clear in the realm of orthopedics to what extent different surface stoichiometric ratios contribute to instigating bioreactive or cytotoxic cellular responses that can lead to aseptic osteolysis. Using energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS), this study presents data and analyses concerning the respective bulk and surface stoichiometric ratios of two commercially pure metal micro-particulates (tantalum and titanium), two prosthetic F75 cobalt–chromium–molybdenum alloy micro-particulates, and prosthetic F136 titanium–aluminum–vanadium alloy micro-particulates, each containing elements common to total joint replacement surgery. Cell culture viability data from four volunteer donors are also presented, which suggest that micro-particulates containing large percentages of surface titanium and aluminum can cause moderate cellular toxicity, and micro-particulates containing large percentages of surface cobalt can result in extremely severe cellular toxicity. This work further suggests that surface analysis techniques, such as XPS, are essential to determine surface elemental characterization of metallic materials prior to interpreting cellular response results.

Co–Cr–Mo alloy particles induce tumor necrosis factor alpha production in MLO-Y4 osteocytes: A role for osteocytes in particle-induced inflammation

Wear debris-induced osteolysis is purportedly the limiting problem affecting the long term results of joint arthroplasty. Pathogenic effects of wear debris in peri-implant cells such as macrophages, osteoblasts and osteoclasts have been well studied. In contrast, the effects of wear debris on osteocytes, which make up over 90% of all bone cells, remain unknown. We hypothesized that metal implant debris can induce the pro-inflammatory response in osteocytes. This study demonstrated the effects of cobalt–chromium–molybdenum alloy (Co–Cr–Mo) particles on a well-characterized MLO-Y4 osteocyte cell line. Co–Cr–Mo alloy particle treatment significantly ( p < 0.05) up-regulated tumor necrosis factor alpha (TNFα) gene expression after 3 and 6 h and TNFα protein production after 24 h, but down-regulated interleukin-6 (IL-6) gene expression after 6 h. Co–Cr–Mo alloy particle treatment also induced osteocyte apoptosis after 24 h. This apoptotic effect was partially (40%) dependent on TNFα. Therefore, our results suggest that osteocytes play a role in particle-induced inflammation and bone resorption following total joint arthroplasty by inducing pro-inflammatory cytokines and inducing osteocyte apoptosis.

B27 Improving Tool Life in End milling of Cobalt Chromium Molybdenum (Co-Cr-Mo) alloy(Advanced machining technology)

B27 Improving Tool Life in End milling of Cobalt Chromium Molybdenum (Co-Cr-Mo) alloy(Advanced machining technology)

Presence of corrosion products and hypersensitivity-associated reactions in periprosthetic tissue after aseptic loosening of total hip replacements with metal bearing surfaces

Aseptic loosening of articular implants is frequently associated with tissue reactions to wear particles. Some patients, who had received metal-on-metal articulations, present early symptoms including persistent pain and implant failure. These symptoms raise the suspicion about the development of an immunological response. Furthermore, the generation of rare corrosion products in association with metallic implants has been observed. Corrosion products are known to enhance third-body wear and contribute to the loss of the implant. The purpose of this study was to investigate periprosthetic tissue containing solid corrosion products after aseptic loosening of second-generation metal-on-metal total hip replacements made of low-carbon cobalt–chromium–molybdenum alloy for the presence of immunologically determined tissue changes. Periprosthetic tissue of 11 cases containing uncommon solid deposits was investigated by light microscopy. In order to confirm the presence of corrosion products, additional methods including scanning electron microscopy (SEM) investigation, energy dispersive X-ray (EDX) and Fourier transform infrared microspectroscopy (FTIR) analysis were used. All investigated cases revealed solid chromium orthophosphate corrosion products as well as metallic wear particles to a various extent. Moreover, various intense tissue reactions characteristic of immune response were observed in all cases. The simultaneous presence of corrosion products and hypersensitivity-associated tissue reaction indicates that a relationship between corrosion development and implant-related hypersensitivity may exist.

Differences in the surface composition of seemingly similar F75 cobalt–chromium micron-sized particulates can affect synovial fibroblast viability

We present data and analyses concerning the cytotoxicity and bioreactivity associated with the surface composition of fine metal particulates that are similar to those commonly released in the body by prostheses used in total joint replacement surgery. Here we study the bulk and surface compositions of three separately procured cobalt–chromium–molybdenum (CoCrMo) micron-sized particulate powders, each identified by their corresponding vendor as being ASTM F75 grade material. We use energy dispersive spectroscopy (EDS) to verify the bulk metallic composition and X-ray photoelectron spectroscopy (XPS) to examine the surface metallic composition of each CoCrMo powder. Cultured synovial fibroblasts were then exposed to the particulate powders to see how the metallic surfaces might affect cellular viability. Results indicate that while the bulk metallic composition of each CoCrMo powder was similar, the surface metallic compositions were found to be dramatically different and yielded equally dramatic differences in terms of cytotoxicity and bioreactivity of synovial fibroblast in culture.

Mechanical load-assisted dissolution of metallic implant surfaces: Influence of contact loads and surface stress state

Mechanical load-assisted dissolution is identified as one of the key mechanisms governing material removal in fretting and crevice corrosion of biomedical implants. In the current study, material removal on a stressed surface of cobalt–chromium–molybdenum (CoCrMo) subjected to single asperity contact is investigated in order to identify the influence of contact loads and in-plane stress state on surface damage mechanisms. The tip of an atomic force microscope is used as a well-characterized “asperity” to apply controlled contact forces and mechanically stimulate the loaded specimen surface in different aqueous environments from passivating to corroding. The volume of the material removed is measured to determine the influence of contact loads, in-plane stresses and the environment on the material dissolution rate. Experimental results indicate that surface damage is initiated at all the contact loads studied and as expected in a wear situation, removal rate increases with increase in contact loads. Removal rates display a complex dependence on residual stresses and the environment. In a passivating environment, the material removal rate is linearly dependent on the stress state such that surface damage is accelerated under compressive stresses and suppressed under tensile stresses. In a corrosive environment, the dissolution rate demonstrates a quadratic dependence on stress, with both compressive and tensile stresses accelerating material dissolution. A surface damage mechanism based on stress-assisted dissolution is proposed to elucidate the experimental observations.

Patch test reactivity to a cobalt–chromium–molybdenum alloy and stainless steel in metal‐allergic patients in correlation to the metal ion release

Nickel, chromium, and cobalt released from stainless steel and CoCrMo alloys have been postulated to trigger hypersensitivity reactions. The objective of this study was to assess the ion release from a CoCrMo alloy and stainless steel in vitro and the cutaneous reactivity to it by patch test. 52 metal-allergic patients and 48 non-allergic controls were patch tested to stainless steel and CoCrMo discs. In addition, using atomic absorption spectrometry, the release of nickel, cobalt, and chromium from both materials was assessed upon 2-day exposure to distilled water, artificial sweat (AS), and cell culture medium. There was low nickel ion release from stainless steel (0.3-0.46 microg/cm(2)/2 days) and CoCrMo discs (up to 0.33 microg/cm(2)/2 days) into the different elution media. Chromium release from the 2 materials was also very low (0.06-0.38 microg/cm(2)/2 days from stainless steel and 0.52-1.36 microg/cm(2)/2 days from CoCrMo alloy). In contrast, AS led to abundant cobalt release (maximally 18.94 microg/cm(2)/2 days) from the CoCrMo discs, with concomitant eczematous reaction upon patch testing: 0 of the 52 metal-allergic patients reacted to stainless steel discs and 5 of the 52 patients to CoCrMo discs (all 5 patients were cobalt allergic and 3 also nickel and chromium allergic). None of the controls reacted to the discs. Apart from nickel being a focus of allergological research, our results point to the possibly underestimated association of cobalt release and potential hyperreactivity to CoCrMo alloy.

Passivation and corrosion behaviours of cobalt and cobalt–chromium–molybdenum alloy

Passivation and corrosion behaviour of the cobalt and cobalt-base alloy Co30Cr6Mo was studied in a simulated physiological solution containing chloride and bicarbonate ions and with pH of 6.8. The oxido-reduction processes included solid state transformations occurring at the cobalt/electrolyte interface are interpreted using theories of surface electrochemistry. The dissolution of cobalt is significantly suppressed by alloying it with chromium and molybdenum, since the alloy exhibited “chromium like” passivity. The structural and protective properties of passive oxide films formed spontaneously at the open circuit potential or during the anodic polarization were studied using electrochemical impedance spectroscopy in the wide frequency range.

Biotribocorrosion of CoCrMo orthopaedic implant materials—Assessing the formation and effect of the biofilm

Due to the renewed interest in hard-on-hard hip replacement, especially metal-on-metal (MoM) or metal-on-ceramic (MoC) joints, issues relating to their long-term durability need to be addressed. Their effects on the operating environment (human body) and how the body fluid affects the implant materials are the primary concern. For widely used metallic implant materials, such as cobalt–chromium–molybdenum (CoCrMo) alloys, released ions due to electrochemical (corrosion) processes and mechanical-enhanced electrochemical (corrosion-wear/tribocorrosion) processes may cause biological reactions in the human hosts. Proteins are a primary constituent of the synovial fluid in human joints with other organic components such as hyaluronic acid and lubricin, and, although numerous tribological studies in protein-containing fluids have been conducted, there is still a need to fully understand the role of proteins and adsorbed-protein layers in wear, corrosion and tribocorrosion processes in artificial joints. In this study, bovine calf serum was used to simulate the body fluid, and a model solution of 0.36% NaCl solution was employed to isolate the influence of organic species (such as proteins, amino acids etc.). Wrought high carbon cobalt–chromium–molybdenum alloy (HC CoCrMo), Wrought low carbon cobalt–chromium–molybdenum alloy (LC CoCrMo) and stainless steel UNS S31603 (316 L) were included in the study and their corrosion, tribology and tribocorrosion behaviour were assessed by integration of gravimetric analysis and electrochemical measurements. Surface analysis (chemical and topographical) was carried out to fully understand the surface/organic species interactions. The constituents of bovine serum have been shown to have a great influence on the corrosion behaviour of all materials studied here—the mechanism of their action being to accelerate ion release and passive film breakdown in static conditions. In tribological contacts, biofilm can play a role in forming an effective lubricating film that reduces friction. For HC CoCrMo, reactions at the surface in the contact zone form a very complex nanostructured layer which comprises wear debris, biofilm and reaction products and the process also changes the nature of the passive film formation. The film reduces the material loss and hence has a protective nature. Organic species (proteins, etc.) were also shown to enhance corrosion-related damage on all materials.

High lubricious surface of cobalt–chromium–molybdenum alloy prepared by grafting poly(2-methacryloyloxyethyl phosphorylcholine)

Osteolysis caused by wear particles from polyethylene in artificial hip joints is of great concern. Various bearing couple combinations, bearing material improvements, and surface modifications have been attempted to reduce such wear particles. With the aim of reducing the wear and developing a novel artificial hip-joint system, we created a highly lubricious metal-bearing material: A 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer was grafted onto the surface of the cobalt–chromium–molybdenum (Co–Cr–Mo) alloy. For ensuring the long-term retention of poly(MPC) on the Co–Cr–Mo alloy, we used a 4-methacryloxyethyl trimellitate anhydride (4-META) intermediate layer and photo-induced graft polymerization technique to create a strong bonding between the Co–Cr–Mo substrate and the poly(MPC) chain via the 4-META layer. The Co–Cr–Mo alloy was pretreated with nitric acid and O 2 plasma to facilitate efficient interaction between the 4-META carboxyl group and the surface hydroxyl group on the Cr oxide passive layer of the Co–Cr–Mo alloy. After MPC grafting, the MPC unit peaks were clearly observed in the Fourier-transform infrared spectroscopy with attenuated total reflection (FT-IR/ATR) and X-ray photoelectron spectroscopy (XPS) spectra of the Co–Cr–Mo surface. Tribological studies with a pin-on-plate machine revealed that surface MPC grafting markedly lowered the friction coefficient. We concluded that the grafted poly(MPC) layer successfully provided high lubricity to the Co–Cr–Mo surface.

Influence on elemental status by hip-endoprostheses

For many clinical purposes various artificial devices are applied, which contact human tissue and can thus cause adverse reactions between prosthetic surfaces and body components. Of the many materials applied for orthopaedic joint replacements the most common are cobalt–chromium–molybdenum alloys. In these cases considerable amounts of cobalt–chromium–molybdenum wear particles are released from the prostheses which have to be regarded as a cause of long-time problems for the patient. Since these particles are dissolved in body fluids of the surrounding area they are distributed in the whole body via blood. Elevated metal concentrations have been found in blood and urine of persons with endoprostheses. Partly the metals are excreted via urine, but to some extend they accumulate in different organs. Therefore this study dealt with the development of an analytical method for the determination of seven relevant trace elements, namely Al, Co, Cr, Mo, Nb, Ni, and Ti in nine kinds of human tissue (brain, heart, kidney, liver, lung, muscle, lymphatic nodes, spleen, body fat) starting with drawing of the sample, sample work up and finally analysis by means of atomic spectrometry. The optimized method was then applied to determine the metal contents in organs of persons (post mortem) with total hip replacements with metal on metal bearing surfaces. Comparison of the data obtained with those of persons without hip-endoprostheses shows that brain and lung are the main targets for elemental accumulation in persons with hip-endoprostheses. Mo and Nb represent the elements with the highest tendency to be accumulated.

Initial Experience with Full-Length Metal Stent to Relieve Malignant Ureteral Obstruction

Ureteral obstruction caused by extrinsic compression by a malignancy generally can be overcome initially with a ureteral stent. However, the long-term failure rate is high, usually necessitating placement of a nephrostomy tube. Herein, we present the initial case, in this country, of intractable ureteral obstruction managed successfully with the newly developed all-metal Resonance stent (Cook Ireland Ltd., Limerick, Ireland) constructed of MP35N alloy, a composite of nonmagnetic nickel-cobalt-chromium-molybdenum. The patient is a 64-year-old woman with metastatic breast cancer causing retroperitoneal fibrosis and ureteral obstruction diagnosed laparoscopically. The obstruction failed to respond to placement of a single 7F double-J stent and then of two 6F double-J stents in the left ureter. As a last resort, in order to avoid nephrostomy-tube placement, the 6F metal stent was placed; this provided unobstructed flow of urine, as documented on a subsequent Whitaker test and, most recently, on a renal scan, 4 months after initial stent placement.

Micro-abrasion–corrosion of a CoCrMo alloy in simulated artificial hip joint environments

This study aims to investigate the synergistic effects of corrosion and wear of artificial human joints made from a surgical grade cast F-75 cobalt–chromium–molybdenum (CoCrMo) alloy. Both electrochemical and gravimetric measurements have been used to determine the performance of CoCrMo samples in static environments and under predominantly three-body abrasive wear conditions using the micro-abrasion test method. Electrochemical measurements are presented from embedded corrosion cells within a micro-abrasion rig. Micro-abrasion–corrosion has been studied using an aggressive abrasive slurry (SiC/Ringer's) to identify depassivation and repassivation processes. These initial conditions are an attempt to simulate worst-case scenarios where wear, cement or bone debris are entrained into the contact. The in situ wear-corrosion measurements have been used to identify the implications of wear and corrosion on both the implant and tentative implications for the patient over the long term. Results show strong synergistic effects occur ranging from negative to positive (i.e. beneficial to accelerated surface removal rates). The synergistic levels appear to be dependent on the integrity of the passive films and the repassivation kinetics. Corrosion potentials are presented which corroborate depassivation within the scar.

Surface analysis of Co–Cr–Mo alloy and Ti substrates silanized with trialkoxysilanes and silane mixtures

AbstractTitanium and cobalt–chromium–molybdenum alloy are widely used inert and biocompatible materials in dentistry and biomedicine. Both materials are non‐degradable and widely relevant in prosthodontics and orthopaedics. The aim of this study was to study the reactions of allyltrimethoxysilane (ALS) and a mixture of allyltrimethoxysilane and 3‐methacryloxypropyltrimethoxysilane (MPS) on Ti and Co–Cr–Mo alloy surfaces. The formation of a uniform, smooth siloxane film, a covalently bonded three‐dimensional Si and O layer, is a prerequisite for the substrate to be bonded with a composite resin. Two silane mixtures of different concentrations were applied onto titanium and Co–Cr–Mo alloy. The silanes were allowed to react with the substrate surface at room temperature and for 1 h at 110 °C. The hypothesis was that a mixture of MPS and ALS could form a uniform, smooth siloxane film on the substrate surface, although ALS is a structurally different trialkoxysilane. Fourier transform infrared spectroscopy, XPS and atomic force microscopy characterization and analysis verified the formation of the siloxane layer on metal substrates, especially on titanium, with silane and silane mixture treatments. Copyright © 2004 John Wiley &amp; Sons, Ltd.

A tribological study of cobalt chromium molybdenum alloys used in metal-on-metal resurfacing hip arthroplasty

Some modern metal-on-metal bearings have undergone early failure and have exhibited a different microstructure from early hip replacement systems that produced very long lifetimes. This has led to investigations as to why different microstructural conditions, from ostensibly the same alloy chemistry, have had differing levels of survival. This paper is concerned with the effect of thermal treatment and hence the resulting microstructure on the wear properties of coupons using a micro-abrasion test. A series of cobalt–chromium–molybdenum (CoCrMo) alloy (ASTM F-75 98, ISO 5832-4: 1996; BS 7252: Part 4: 1997) sample coupons with different combinations of thermal treatments (solution heat treatment, hot isostatic pressing or sintering) were studied. Metallographic studies have been used to determine the volume fraction of carbide present. The carbide level and morphology varied markedly between samples with respect to thermal history. This work has established that microstructure and in particular the volume fraction, size and distribution of carbides is critical to the development of a low wear rate system. As-cast materials were determined to have greater abrasive wear resistance when compared to single or multiple heat treated materials.

Biocoating of Electropolished and Ultra‐Hydrophilic Titanium and Cobalt Chromium Molybdenum Alloy Surfaces with Proteins

AbstractBone morphogenetic proteins (BMPs) play a decisive role in bone development and osteogenesis. In the past they have been the subject of widespread research and clinical trials as stimulants of bone growth. Although recently recombinant human BMP‐2 (rhBMP‐2) has been chemically immobilized on implant surfaces leading to enhanced bone growth and accelerated integration in vivo, the non‐covalent immobilization of proteins on metal surfaces is still poorly understood, since the oxide layers on metals like titanium, stainless steel or cobalt chromium alloys are poor adsorbents of proteins. Protein binding surfaces could either be generated by linking ionic groups (ion‐exchange surface) or by coupling hydrophobic residues (hydrophobic interacting surface, HIS) to the surface. In this paper the preparation of protein adsorbing surfaces on titanium and cobalt chromium molybdenum alloy for the adsorption of rhBMP‐2 and ubiquitin will be described. rhBMP‐2 and ubiquitin are bound extremely tight to surfaces containing propyl or hexyl groups of a certain surface concentration and are slowly released over a range of at least 24–100 days making such surfaces applicable as long‐term drug delivery devices for enhancing bone growth or implant integration.

Orthopaedic implant related metal toxicity in terms of human lymphocyte reactivity to metal-protein complexes produced from cobalt-base and titanium-base implant alloy degradation.

Metal toxicity from sources such as orthopaedic implants was investigated in terms of immune system hyper-reactivity to metal implant alloy degradation products. Lymphocyte response to serum protein complexed with metal from implant alloy degradation was investigated in this in vitro study using primary human lymphocytes from healthy volunteers (n = 10). Cobalt chromium molybdenum alloy (Co-Cr-Mo, ASTM F-75) and titanium alloy (Ti-6Al-4V, ASTM F-136) beads (70 microm) were incubated in agitated human serum at 37 degrees Celsius to simulate naturally occurring metal implant alloy degradation processes. Particulate free serum samples, which were incubated with metal, were then separated into molecular weight based fractions. The amounts of soluble Cr and Ti within each serum fraction were measured and correlated with lymphocyte proliferation response to the individual serum fractions. Lymphocytes from each subject were cultured with 11 autologous molecular weight based serum fractions either with or without added metal. Two molecular weight ranges of human serum proteins were associated with the binding of Cr and Ti from Co-Cr-Mo and Ti implant alloy degradation (at < 30 and 180-330 kDa). High molecular weight serum proteins (approximately 180 kDa) demonstrated greater lymphocyte reactivity when complexed with metal released from Co-Cr-Mo alloy and Ti alloy than with low (5-30 kDa) and midrange (30-77 kDa) serum proteins. When the amount of lymphocyte stimulation was normalized to both the moles of metal and the moles of protein within each fraction (Metal-Protein Complex Reactivity Index, MPCRI), Cr from Co-Cr-Mo alloy degradation demonstrated approximately 10 fold greater reactivity than Ti in the higher molecular weight serum proteins (approximately 180-250 kDa). This in vitro study demonstrated a lymphocyte proliferative response to both Co-Cr-Mo and Ti alloy metalloprotein degradation products. This response was greatest when the metals were complexed with high molecular weight proteins, and with metal-protein complexes formed from Co-Cr-Mo alloy degradation.