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Acta of Bioengineering and Biomechanics; 04/2017; ISSN 1509-409X

Two categories of joint overloading cause post-traumatic osteoarthritis (PTOA): single acute traumatic loads/impactions and repetitive overloading due to incongruity/instability. We developed and refined three classes of complementary models to define relationships between joint overloading and progressive cartilage loss across the spectrum of acute injuries and chronic joint abnormalities: explant and whole joint models that allow probing of cellular responses to mechanical injury and contact stresses, animal models that enable study of PTOA pathways in living joints and pre-clinical testing of treatments, and patient-specific computational models that define the overloading that causes OA in humans. We coordinated methodologies across models so that results from each informed the others, maximizing the benefit of this complementary approach. We are incorporating results from these investigations into biomathematical models to provide predictions of PTOA risk and guide treatment. Each approach has limitations, but each provides opportunities to elucidate PTOA pathogenesis. Taken together, they help define levels of joint overloading that cause cartilage destruction, show that both forms of overloading can act through the same biologic pathways, and create a framework for initiating clinical interventions that decrease PTOA risk. Considered collectively, studies extending from explants to humans show that thresholds of joint overloading that cause cartilage loss can be defined, that to at least some extent both forms of joint overloading act through the same biologic pathways, and interventions that interrupt these pathways prevent cartilage damage. These observations suggest that treatments that decrease the risk of all forms of OA progression can be discovered. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:515-523, 2017.

In contemporary total hip arthroplasty, instability has been a complication in approximately 2% to 5% of primary surgeries and 5% to 10% of revisions. Due to the reduction in the incidence of wear-induced osteolysis that has been achieved over the last decade, instability now stands as the single most common reason for revision surgery. Moreover, even without frank dislocation, impingement and subluxation are implicated in a set of new concerns arising with advanced bearings, associated with the relatively unforgiving nature of many of those designs. Against that backdrop, the biomechanical factors responsible for impingement, subluxation, and dislocation remain under-investigated relative to their burden of morbidity. This manuscript outlines a 15-year program of laboratory and clinical research undertaken to improve the scientific basis for understanding total hip impingement and dislocation. The broad theme has been to systematically evaluate the role of surgical factors, implant design factors, and patient factors in predisposing total hip constructs to impinge, sublux, and/or dislocate. Because this class of adverse biomechanical events had not lent itself well to study with existing approaches, it was necessary to develop (and validate) a series of new research methodologies, relying heavily on advanced finite element formulations. Specific areas of focus have included identifying the biomechanical challenges posed by dislocation-prone patient activities, quantifying design parameter effects and component surgical positioning effects for conventional metal-on-polyethylene implant constructs, and the impingement/dislocation behavior of non-conventional constructs, quantifying the stabilizing role of the hip capsule (and of surgical repairs of capsule defects), and systematically studying impingement and edge loading of hard-on-hard bearings, fracture of ceramic liners, confounding effects of patient obesity, and subluxation-mediated worsening of third body particle challenge.

Dislocation remains a serious concern for total hip arthroplasty (THA). Impingement, typically between the implant femoral neck and the acetabular cup, remains the most common dislocation impetus. Wear reductions from recent bearing technology advancements have encouraged introduction of substantially increased femoral head diameters. However, there is some evidence that range of motion with larger head sizes is limited by bone-on-bone, rather than hardware, impingement. While all impingement events are of course undesirable, currently little is known biomechanically if these two impingement modes differ in terms of generation of potentially deleterious stress concentrations or with regard to dislocation resistance. Finite element (FE) analysis was therefore used to parametrically investigate the role of head diameter on the local biomechanics of bone-on-bone versus component-on-component impingement events. Of several dislocation-prone patient motion challenges considered, only squatting consistently resulted in bone-on-bone (as opposed to hardware) impingement. Implant stress concentrations arising from hardware impingement during squatting were greater than those from bony impingement, for all head sizes considered. Additionally, dislocation resistance was substantially greater for instances of bony impingement versus hardware-only impingement. These findings suggest that hardware impingement may still be a/the the predominant mode of impingement even with the use of larger femoral heads, for sub-optimally positioned cups. Additionally, the data indicate that, should impingement occur, impingements between the implant neck and cup are (1) more likely to dislocate, and (2) have a greater propensity for causing damage to the implant compared to impingement events involving bony members.

While favorable tribological properties and allowance for larger femoral head sizes have made metal-on-metal bearings an increasingly popular choice for total hip arthroplasty, concerns have mounted regarding adverse reactions to metal wear debris and ions. Metal-on-metal cups differ from conventional polyethylene cups in terms of edge profile design and reductions from full hemisphericity, suggesting differences in loading at or near the cup edge, especially during subluxation events. Finite element analysis was used to investigate the effects of cup orientation and lip edge curvature on damage propensity for edge or near-edge loading during subluxation. Increased cup lip radius (resulting in reduced articular arc) had a detrimental effect upon subluxation-free hip range of motion and upon dislocation resistance. Contact stresses near the cup edge demonstrated complex relationships between edge radius and cup orientation, with peak stresses being influenced by both variables. The tendency for scraping wear at the egress site demonstrated similarly complex dependencies. These data indicate that acetabular cup design is an important determinant of edge and near-edge loading damage propensity.

Investigation of femoral head osteonecrosis would benefit from an animal model whose natural history includes progression to bony collapse of a segmental necrotic lesion. The bipedal emu holds attraction for systematic organ-level study of collapse mechanopathology. One established method of experimentally inducing segmental lesions is liquid nitrogen cryoinsult. Four cryoinsult parameters – hold temperature, freeze duration, freeze/thaw repetition, and thaw duration - were investigated to determine their individual and combined effects on resulting necrotic lesion morphology. 3D distributions of histologically-apparent osteocyte necrosis from 24 emus receiving varying cryoinsults were used to develop univariate and multivariate linear regression models relating resulting necrotic lesion morphology to particular cryoinsult input parameters. These models were then applied to predict lesion size in four additional emus receiving differing input cryoinsults. The best multivariate regression model predicted lesion volumes that were accurate to better than 8% of overall emu femoral head volume. The hold temperature during cryoinsult was by far the most influential cryoinsult input parameter. The utility of this information is to enhance the consistency and predictability of cryoinsult-induced segmental lesion size for the purposes of systematic laboratory studies at the whole-organ level.

With a rise in post-traumatic osteoarthritis, OA no longer is considered just a disease of aging. The 'gold standard' for OA diagnosis has long been planar radiographs for visualizing osteophytes, joint space narrowing and sclerotic changes. A typical magnetic resonance imaging (MRI) protocol will acquire proton density, T1, T2, and fat suppressed images that give a comprehensive picture of morphologic changes associated with injury and subsequent degenerative processes. However, the earliest events of cartilage degeneration occur within the tissue, before measureable changes in morphology. MRI methods have been proposed to display and quantify changes in composition and integrity of such elements of cartilage extracellular matrix as collagen and proteoglycan (PG) content in vivo. T1ρ the spin-lattice relaxation time in the rotating frame, has come to the forefront for visualizing water proton-PG interactions in articular cartilage. The purpose of this T1ρ MRI study was to define an objective femoral condyle-specific registration method, in which zone-dependent cartilage compositional changes could be assessed from the bone outward through the existing cartilage, at pre-ACL reconstruction and subsequent follow-up times, when the loss of thickness to surface-down cartilage erosion might occur later in the OA pathogenesis. Additionally, this study explores the effects of reducing the number of spin-lock times on the absolute T1ρ relaxation times; a major parameter in expanding T1ρ coverage to the whole joint while satisfying clinical imaging time and specific absorption rate (SAR) safety constraints. The developed image analysis tools serve as the first step toward quantitative functional assessment of cartilage health with noninvasive T1ρ MRI, which has the potential to become an important new tool for the early diagnosis of cartilage degeneration following ACL trauma.

Piezoresistive array pressure sensors are widely used in orthopaedic research to determine contact stress distributions across articular joint surfaces. Experience with such sensors has shown there can be inaccuracies in how the sensor perceives applied load, depending on the material stiffnesses between which it is compressed experimentally, versus in calibration. A study was undertaken to quantify the relationship between load perception of one such sensor design (Tekscan) and the stiffness of the materials between which it is compressed. A three-dimensional finite element model of a 3x3 sensel portion of the sensing matrix was formulated, along with a layer of compression test material on each side of the sensor. The elastic modulus of the test material was varied across the range representative of cartilage (12 MPa) to hard plastic (10 GPa). Using the computed contact pressure results between contacting surfaces of the sensor layers, the percentage of load passing through the active conductor intersections was determined. The results revealed that with increase of the elastic modulus of the material between which the sensor was compressed, the percentage of load on the active conductor intersections increased monotonically. The highest sensitivity of perceived loading to test material modulus (0.1%/MPa) was seen at the low end of the modulus range. The more compliant the test material, the more the sensor layers conformed around each other's geometric incongruities, the larger the true contact areas, and the higher the fraction of the total load that passed through the intermediate (non-sensing) regions between the conductors.