The use of spinal implants has been steadily increasing over the last 20 years, with the number of cervical and lumber fusions in the US increasing 111% to roughly 105 fusions per 100,000 people or approximately 305,000 fusions per year, from 1993 to 2003.1 This represents a large market force driving the development of new types of spinal implants such as total disc arthroplasties (TDA) or intervertebral disc replacements (IDR) and new biologic treatment modalities. Ultimately, new technologies, such as intervertebral disc replacement, seek to replace spine fusion by both eliminating pain and preserving spinal mobility (flexion-extension, lateral-bending, and rotation). Central to the assessment of device safety and efficacy is simulator testing prior to clinical evaluation. The utility of simulator analysis is generally twofold where (1) the amount of implant wear and degradation is assessed through the measurement of implant weight loss (gravimetric loss) and physical examination, and (2) the type of wear and corrosion debris is characterized to assess potential bioreactivity. Simulator testing for articulating total disc implants or dynamic stabilization devices is generally conducted up to 10 million cycles under loading and motion appropriate to the implant in question under the guidelines of ASTM F2423, ASTM F1717, and 2008 Investigational Device Exemption guidelines of the US Food and Drug Administration (FDA).

Understanding the gravimetric weight loss and the type of debris resulting from in vitro simulator testing is critical in predicting how an implant will perform in vivo and how much debris should be used in an animal model, prior to clinical study.

Traditional hip and knee arthroplasties enjoy a relatively high degree of standardization for predictive wear testing over the last 35 years, yet to date there remains an unclear relationship between simulator fluid composition and the effect on wear rate of different material couples in arthroplasty testing (see Table 1).2–5 Generally, motionsparing spine implants lack a lengthy history of empirical testing, while simultaneously posing novel and unique requirements that complicate the prediction of wear. One of these novel requirements is the increasing number of connected components and thereby the increasing complexity of articulating spinal implants when compared with traditional total hip and knee implants. Geometrical considerations of some of these designs increasingly preclude the use of serum protein-supplemented simulator fluid testing. The reason for this is that protein in serum tends to penetrate into the crevices or compartments of multicomponent devices (including protective sheaths) and then either adsorbs onto material surface or cannot be practically cleaned during weight loss measurement, thus preventing accurate gravimetric measurement of weight loss during the course of simulator testing. This complication is due to the impossibility of removing proteins from all interfaces without damaging the implants during testing.

The use of saline fluid without serum is one alternative, although without the protective effects of serum as a lubricant, articulating devices generally produce more wear under “all saline” conditions.6 However, with little clinical data to compare with in vitro testing it remains unknown how the accurate prediction of wear debris from motion-preserving spinal implants depends on using appropriate simulator fluids for given articulating surfaces and implant constructs.

Our initial hypothesis was that simulator testing of a posterior dynamic stabilization implant that has metal-onmetal articulating bearings will not produce dramatically different wear debris when tested using pure saline versus testing in saline supplemented with 20% serum. To test this hypothesis we examined the type and amount of wear debris generated from a dynamic stabilization spinal implant using in vitro simulator testing in saline-only and in 20% serum-supplemented-saline simulator fluid over the course of 10 million cycles.

Our initial hypothesis, that 100% saline versus 20% serum simulator lubricants would not cause a significant difference in the amount of gravimetric weight loss, was not supported by the data when tested using a spinal dynamic stabilization implant with metal-on-metal bearings. On the contrary there was greater than 100-fold increase in the amount of wear generated in the salineonly when compared to the 20% serum, as determined by weight loss, ie, gravimetrically. In addition, there were marked differences in the average size and the type of wear debris that were directly and mechanistically attributable to the type of simulator fluid used, where smaller particles of chromium oxide were evident in the saline simulator fluids when compared to serum (Average sizes: Serum = 3.2 microns diameter, Saline = 0.2 microns diameter), indicative of fretting corrosion. Saline resulted in high amounts of released Co-Cr oxide debris indicative of a fretting-like corrosion phenomenon.

Fretting corrosion generally occurs at modular junctions (connections) of any loaded orthopedic implant to some degree and is typically produced by relatively smallscale (1 – 100 µm) motion between implant components induced by cyclic loading. However, all that is required to produce fretting type corrosion is the continual fracture and reformation of oxide layers (repassivation), which form over metal surfaces of implants (or any metal in a corrosive environment) causing a O₂-depleted microenvironment, thereby accelerating corrosion reactions within the crevices or any location where oxygen reduction can be maintained. This process is driven by the reduction in free energy associated with ceramic layer forming on the metal surface (metal-oxide formation) which results in the sequestration of O2 from any available source (primarily H₂O).9, 10

Since implant fretting corrosion was first identified in the late 1950s,11, 12 many investigations have characterized fretting of implant materials.9, 13–22 Past studies have shown markedly different rates of fretting associated with saline and proteinaceous solutions.23, 24 Generally, decreased rates of fretting corrosion have been observed in proteinaceous solutions when compared to levels of fretting weight loss in physiologic saline solutions, similar to the results found in the current investigation.

Thus testing in pure saline likely produced an artificially high amount of corrosion/wear debris (weight loss), compared to what would likely occur in vivo where generally 100% serum conditions exist. To date there are no clinical reports of wear rates in dynamic stabilization implants. It remains unknown how the “protective” effect of serum proteins at the ASTM standard of 20% of the simulator lubricant will affect the wear of this metal-onmetal articulating spinal implant and how it would vary at increasing concentrations up to 100%. However, the weight gain witnessed in this study of a highly modular component is likely the consequence of protein and/or liquid penetrating tight junctions of the component that generally accumulate over the course of testing. This was indicated by the lack of weight gain in the load-soak controls where after immersion time equivalent to 10 million cycles there was no indication that protein build-up was the result of passive adsorption onto the exposed external surfaces on the implants, but instead was likely due to protein build-up within crevices/modular connections available for protein deposition only during cyclic loading of the implants. These phenomena of weight gain, protein adsorption, and crevice accessibility during simulator testing will likely become more common with increasing numbers of multicomponent implant designs. Ultimately the end result of this protein/fluid accumulation in modular junctions may mask wear/corrosion degradation that takes place during the gravimetric weighing of the implants over the course of testing.

The results of this study illustrate the modern testing predicament in the assessment of wear/corrosion of a multicomponent spinal implant using in vitro mechanical simulation. While pure saline produced non-physiologically high amounts of wear/corrosion debris, the addition of serum (20%) resulted in masking any wear/corrosion that took place. It is likely that testing should be conducted at a non-ASTM and -ISO standard level of serum protein less than 20%. The exact composition would likely vary from implant to implant, where geometrical considerations may be more or less dominant. However, when assessing the physiologic importance of wear/corrosion testing, pure saline clearly represents a non-physiologic “worst case” scenario, when compared to the in vivo data from metal-on-metal total hip and disc arthroplasties since clinical data for this implant is not currently available. However the degree to which results of testing in pure saline can be appropriately scaled down to approximate in vivo conditions is not known and leaves open the question of “to what degree do the results of testing in pure saline (the only conditions to produce significant degradation) relate to in vivo degradation and implant performance?” The only definitive answer to this question lies in the evaluation of available retrieved implants after years of clinical use.

However, one way to assess the performance of modular spinal implants with metal-on-metal articulation in saline (worst case) is to compare them to the results of other metal-on-metal implants.

Wear is generally measured gravimetrically, using the weight loss of an implant over the course of testing. However, because of density variations between materials, the amount of wear between different implants is compared using a volumetric wear basis (adjusting the mass loss to volume using the average density of the implant materials). Because of the different implant geometries and surface areas, linear penetration, as is used in some studies, is an inappropriate measure of wear and when comparing different types of implants. Also important to wear characteristics of a particular implant is the average size of the debris particles, as the debris size will determine the numbers of particles that are generated from a given amount of wear volume. Generally the greater the numbers of particles the greater the untoward biologic response will be.

There are relatively few published reports on the in vivo wear rates of articulating spine implants in general, and even fewer report of those with metal-on-metal articulating surfaces to compare the results of the current investigation to.4, 5, 25 However, a recent in vitro study of the metal-onmetal total disc arthroplasty implant by Pare et al using a spine simulator (flexion-extension ±10° at a constant load of 1200 N in 11.5 g/L protein up to 10 million cycles) found a volumetric wear rate of 1.26 mm³ per million cycles (Figure 13).25 Other similar studies of estimated total wear volume of an intervertebral disc prosthesis with an all titanium-6%Al-4%V alloy was reported to be 2.9 mm³/million cycles.4 The volumetric rate of “worst case” wear/corrosion using saline in this study was 2.5 mm³/million cycles, which was less than that reported for Ti-alloy spinal components but more than that reported for a cobalt alloy metal-on-metal disc arthroplasty implant tested in serum-supplemented saline.25 The lack of measurable wear in 20% serum of the dynamic stabilization device in this study implies that factors such as less direct loading and decreased articulation (sliding) when compared to total disc arthroplasty implants may result in less wear, if other factors like fretting corrosion do not become dominant in vivo.

Inflammatory response to particles is generally determined by the particle load (ie, number of particles). This load or number of phagocytosable particles released is determined by both the average size of the particles (smaller particle size = more particles for a given volume loss) and total volume of wear debris (the more volume lost = more particles of a given size).26, 27 If a given amount of debris is comprised of smaller diameter particles (within the 0.1-10 µm range) it is by virtue of their greater numbers per volume that they induce more of a proinflammatory response than the larger particulates.27 However on a particle-to-particle basis (ie, equal numbers of the large and smaller size particles), the degree to which smaller or larger particles will induce a response has not been thoroughly investigated and remains unknown. What is clear is that the numbers of particles produced by the current implant in saline would have a far greater biologic response than the particles produced in serum, by virtue of their vastly greater numbers at the same cycle counts (roughly at least a > 10⁶-fold increase in numbers of particles).

Another important component of particle characterization is the degree to which large particles comprise the total volume of the debris. Large (> 10 µm) particles were evident in both fluid environments demonstrating the importance of using a particle characterization method such as LALLS which samples millions/billions of particles to statistically “catch” the larger size particles that contribute significantly to the overall volume or weight loss but are not observed on a number distribution because the make-up is a negligible percent of the total number of particles. Identifying the presence of large particles within a given amount of debris effectively reduces the overall particle burden (number) because larger particles make up a disproportionately high percentage of the total volume. A single 100 micron diameter particle equals the same volume as 1 million 1 micron diameters particles. So identifying just how much of the total volume of debris is comprised of larger particles is important to calculating how many particles were generated from a given implant for a given amount of volume loss.

It is generally established that the related phenomena of aseptic loosening and periprosthetic osteolysis (the most common reasons for revision surgery) are a consequence of the host response to the amount of debris originating from prosthetic devices (numbers of particles).28 The majority of this debris originates from articulating surfaces. For the current implant, the results of the average distributions of particle sizes over 10 million cycles (volume-based distributions to factor in larger particles) were used to calculate the total number of particles generated which was approximately 2.5×10⁸ particles/mg (2 × 10⁹ particles/mm³) of Co-alloy debris and equates to approximately 485 × 10⁸ particles per 10 million cycles (average weight loss was 194 mg). This amount of wear debris (194 mg or approximately 24 mm³ of lost volume) corresponds to approximately 2.4 mm³ of lost volume per 1 million cycles (or per year based on a an assumed cycle load of 1 million bends per year). This is within the range of other spine arthroplasty implants (Figure 13)4, 29–36 and well below the wear of other metal-on-metal or metal-on-polymer total joint arthroplasty implants (Figure 13).29–36

There were significant differences in gravimetric wear, average size and type of wear debris that were mechanistically attributable to the type of simulator fluid used (ie, corrosion versus abrasive wear). Large (> 10 µm) particles were evident in both fluid environments demonstrating the importance of non-number based analysis methodologies. Pure saline resulted in nonphysiologically high Cr-Co fretting-like corrosion debris and 20% serum resulted in Co-Cr debris that was below gravimetric method detection limits (10 mg over 10 million cycles). This highlights the practical limitations in simulator testing and the importance of interpreting wear and corrosion data in the appropriate context, ie, testing conditions. The overprotective effect of serum proteins appears to underscore the importance of using both saline and serum when establishing upper and lower bounds of predictive implant debris generation modeling, where saline represents a worst case scenario and as little as 20% serum masks all weight loss completely. The fact that serum protein adsorption can mask wear suggests that wear testing highly modular, articulating spine implants can be problematic, especially under conditions of low but significant wear. Simulator testing conducted in serum alone may not adequately indicate actual weight loss or debris generation, which may translate to more debris released clinically than predicted. Thus, care should be taken in the interpretation of results of modular articulating implants tested in serum-supplemented simulator fluids.