Ceramic Wear Particles: Can They Be Retrieved In Vivo and Duplicated In Vitro?

BACKGROUND: Little is known about retrieved zirconia platelet toughened alumina (ZPTA) wear particles from ceramic-on-ceramic (COC) total hip arthroplasty. Our objectives were to evaluate clinically retrieved wear particles from explanted periprosthetic hip tissues and to analyze the characteristics of in vitro-generated ZPTA wear particles. METHODS: Periprosthetic tissue and explants were received for 3 patients who underwent a total hip replacement of ZPTA COC head and liner. Wear particles were isolated and characterized via scanning electron microscopy and energy dispersive spectroscopy. The ZPTA and control (highly cross-linked polyethylene and cobalt chromium alloy) were then generated in vitro using a hip simulator and pin-on-disc testing, respectively. Particles were assessed in accordance with American Society for Testing and Materials F1877. RESULTS: Minimal ceramic particles were identified in the retrieved tissue, consistent with the retrieved components demonstrating minimal abrasive wear with material transfer. Average particle diameter from in vitro studies was 292 nm for ZPTA, 190 nm for highly cross-linked polyethylene, and 201 nm for cobalt chromium alloy. CONCLUSION: The minimal number of in vivo ZPTA wear particles observed is consistent with the successful tribological history of COC total hip arthroplasties. Due to the relatively few ceramic particles located in the retrieved tissue, in part due to implantation times of 3 to 6 years, a statistical comparison was unable to be made between the in vivo particles and the in vitro-generated ZPTA particles. However, the study provided further insight into the size and morphological characteristics of ZPTA particles generated from clinically relevant in vitro test setups.

Height restoration and sustainability using bilateral vertebral augmentation systems for vertebral compression fractures: a cadaveric study.

BACKGROUND CONTEXT: The treatment of vertebral compression fractures using percutaneous augmentation is an effective method to reduce pain and decrease mortality rates. Surgical methods include vertebroplasty, kyphoplasty, and vertebral augmentation with implants. A previous study suggested that a titanium implantable vertebral augmentation device (TIVAD) produced superior height restoration compared to balloon kyphoplasty (BKP) but was based on a less clinically relevant biomechanical model. Moreover, the introduction of high pressure balloons and directional instruments may further aid in restoring height. PURPOSE: The objective was to evaluate three procedures (BKP, BKP w/ Kyphon Assist (KA; directional instruments), and TIVAD) used for percutaneous augmentation of vertebral fractures with respect to height restoration and sustainability post-operatively. STUDY DESIGN/SETTING: This is an in vitro cadaver study performed in a laboratory setting. METHODS: Five osteoporotic female human cadaver thoracolumbar spines (age: 63-77 years, T-score: -2.5 to -3.5, levels: T7-S1) were scanned using computed tomography and dissected into 30 two-functional spine units (2FSUs). Vertebral wedge compression fractures were created by reducing the anterior height of the vertebrae by 25% and holding the maximum displacement for 15 minutes. Post-fracture, surgery was performed on each 2FSU with a constant 100 N load. Surgeries included BKP, BKP w/ KA, or TIVAD (n=10 per treatment group). Post-surgery, cyclic loading was performed on each 2FSU for 10,000 cycles at 600 N (walking), followed by 5,000 cycles at 850 N (standing up/sitting down), and 5,000 cycles at 1250 N (lifting a 5-10kg weight from the floor). Fluoroscopic images were taken and analyzed at the initial, post-fracture, post-surgery, and post-loading timepoints. Anterior, central, and posterior heights, Beck Index, and angle between endplates were assessed. RESULTS: No difference in height restoration was observed among treatment groups (p=.72). Compared to the initial height, post-surgery anterior height was 96.3±8.7% for BKP, 94.0±10.0% for BKP w/ KA, and 95.3±5.8% for TIVAD. No difference in height sustainability in response to 600 N (p=.76) and 850 N (p=.20) load levels was observed among treatment groups. However, after 1250 N loading, anterior height decreased to 93.8±6.8% of the post-surgery height for BKP, 95.9±6.4% for BKP w/ KA, and 86.0±6.6% for TIVAD (p=.02). Specifically, the mean anterior height reduction between post-surgery and post-1250 N loading timepoints was lower for BKP w/ KA compared to TIVAD (p=.02), but not when comparing BKP to TIVAD (p=.07). No difference in Beck Index or angle between endplates was observed at any timepoint among the treatment groups. CONCLUSIONS: The present study, utilizing a clinically relevant biomechanical model, demonstrated equivalent height restoration post-surgery and at relatively lower-level cyclic loading using BKP, BKP w/ KA, and TIVAD, contrary to results from a previous study. Less anterior height reduction in response to high-level cyclic loading was observed in the BKP w/ KA group compared to TIVAD. CLINICAL SIGNIFICANCE: All three treatments can restore height similarly after a vertebral compression fracture, which may lead to pain reduction and decreased mortality. BKP w/ KA may exhibit less height loss in higher-demand patients who engage in physical activities that involve increased weight resistance.

Low bone mass resulting from impaired estrogen signaling in bone increases severity of load-induced osteoarthritis in female mice.

OBJECTIVE: Reduced subchondral bone mass and increased remodeling are associated with early stage OA. However, the direct effect of low subchondral bone mass on the risk and severity of OA development is unclear. We sought to determine the role of low bone mass resulting from a bone-specific loss of estrogen signaling in load-induced OA development using female osteoblast-specific estrogen receptor-alpha knockout (pOC-ERαKO) mice. METHODS: Osteoarthritis was induced by cyclic mechanical loading applied to the left tibia of 26-week-old female pOC-ERαKO and littermate control mice at peak loads of 6.5N, 7N, or 9N for 2 weeks. Cartilage damage and thickness, osteophyte development, and joint capsule fibrosis were assessed from histological sections. Subchondral bone morphology was analyzed by microCT. The correlation between OA severity and intrinsic bone parameters was determined. RESULTS: The loss of ERα in bone resulted in an osteopenic subchondral bone phenotype, but did not directly affect cartilage health. Following two weeks of cyclic tibial loading to induce OA pathology, pOC-ERαKO mice developed more severe cartilage damage, larger osteophytes, and greater joint capsule fibrosis compared to littermate controls. Intrinsic bone parameters negatively correlated with measures of OA severity in loaded limbs. CONCLUSIONS: Subchondral bone osteopenia resulting from bone-specific loss of estrogen signaling was associated with increased severity of load-induced OA pathology, suggesting that reduced subchondral bone mass directly exacerbates load-induced OA development. Bone-specific changes associated with estrogen loss may contribute to the increased incidence of OA in post-menopausal women.

Injectable mechanical pillows for attenuation of load-induced post-traumatic osteoarthritis.

Osteoarthritis (OA) of the knee joint is a degenerative disease initiated by mechanical stress that affects millions of individuals. The disease manifests as joint damage and synovial inflammation. Post-traumatic osteoarthritis (PTOA) is a specific form of OA caused by mechanical trauma to the joint. The progression of PTOA is prevented by immediate post-injury therapeutic intervention. Intra-articular injection of anti-inflammatory therapeutics (e.g. corticosteroids) is a common treatment option for OA before end-stage surgical intervention. However, the efficacy of intra-articular injection is limited due to poor drug retention time in the joint space and the variable efficacy of corticosteroids. Here, we endeavored to characterize a four-arm maleimide-functionalized polyethylene glycol (PEG-4MAL) hydrogel system as a 'mechanical pillow' to cushion the load-bearing joint, withstand repetitive loading and improve the efficacy of intra-articular injections of nanoparticles containing dexamethasone, an anti-inflammatory agent. PEG-4MAL hydrogels maintained their mechanical properties after physiologically relevant cyclic compression and released therapeutic payload in an on-demand manner under in vitro inflammatory conditions. Importantly, the on-demand hydrogels did not release nanoparticles under repetitive mechanical loading as experienced by daily walking. Although dexamethasone had minimal protective effects on OA-like pathology in our studies, the PEG-4MAL hydrogel functioned as a mechanical pillow to protect the knee joint from cartilage degradation and inhibit osteophyte formation in an in vivo load-induced OA mouse model.

Mechanobiological Mechanisms of Load-Induced Osteoarthritis in the Mouse Knee.

Osteoarthritis (OA) is a degenerative joint disease that affects millions of people worldwide, yet its disease mechanism is not clearly understood. Animal models have been established to study disease progression by initiating OA through modified joint mechanics or altered biological activity within the joint. However, animal models often do not have the capability to directly relate the mechanical environment to joint damage. This review focuses on a novel in vivo approach based on controlled, cyclic tibial compression to induce OA in the mouse knee. First, we discuss the development of the load-induced OA model, its different loading configurations, and other techniques used by research laboratories around the world. Next, we review the lessons learned regarding the mechanobiological mechanisms of load-induced OA and relate these findings to the current understanding of the disease. Then, we discuss the role of specific genetic and cellular pathways involved in load-induced OA progression and the contribution of altered tissue properties to the joint response to mechanical loading. Finally, we propose using this approach to test the therapeutic efficacy of novel treatment strategies for OA. Ultimately, elucidating the mechanobiological mechanisms of load-induced OA will aid in developing targeted treatments for this disabling disease.

Collagen XI mutation lowers susceptibility to load-induced cartilage damage in mice.

Interactions among risk factors for osteoarthritis (OA) are not well understood. We investigated the combined impact of two prevalent risk factors: mechanical loading and genetically abnormal cartilage tissue properties. We used cyclic tibial compression to simulate mechanical loading in the cho/+ (Col11a1 haploinsufficient) mouse, which has abnormal collagen fibrils in cartilage due to a point mutation in the Col11a1 gene. We hypothesized that the mutant collagen would not alter phenotypic bone properties and that cho/+ mice, which develop early onset OA, would develop enhanced load-induced cartilage damage compared to their littermates. To test our hypotheses, we applied cyclic compression to the left tibiae of 6-month-old cho/+ male mice and wild-type (WT) littermates for 1, 2, and 6 weeks at moderate (4.5 N) and high (9.0 N) peak load magnitudes. We then characterized load-induced cartilage and bone changes by histology, microcomputed tomography, and immunohistochemistry. Prior to loading, cho/+ mice had less dense, thinner cortical bone compared to WT littermates. In addition, in loaded and non-loaded limbs, cho/+ mice had thicker cartilage. With high loads, cho/+ mice experienced less load-induced cartilage damage at all time points and displayed decreased matrix metalloproteinase (MMP)-13 levels compared to WT littermates. The thinner, less dense cortical bone and thicker cartilage were unexpected and may have contributed to the reduced severity of load-induced cartilage damage in cho/+ mice. Furthermore, the spontaneous proteoglycan loss resulting from the mutant collagen XI was not additive to cartilage damage from mechanical loading, suggesting that these risk factors act through independent pathways. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:711-720, 2018.

Trunk and Shank Position Influences Patellofemoral Joint Stress in the Lead and Trail Limbs During the Forward Lunge Exercise.

Study Design Controlled laboratory study, repeated-measures design. Background The effects of trunk and shank position on patellofemoral joint stress of the lead limb have been well studied; however, the effects on the trail limb are not well understood. Objectives To test the hypothesis that trunk and shank position may influence patellofemoral joint stress in both limbs during the forward lunge exercise. Methods Patellofemoral kinetics were quantified from 18 healthy participants performing the lunge exercise with different combinations of trunk and shank positions (vertical or forward). A 2-by-3 (limb-by-lunge variation) repeated-measures analysis of variance was performed, using paired t tests for post hoc comparisons. Results The trail limb experienced greater total patellofemoral joint stress relative to the lead limb, regardless of trunk and shank position (P<.0001). The lunge variation with a vertical shank position resulted in significantly greater peak patellofemoral joint stress in the trail limb relative to the lead limb (P<.0001). A forward trunk and shank position resulted in the highest patellofemoral stress in the lead limb (P<.0001). Conclusion Trunk and shank positions have a significant influence on patellofemoral joint loading of both limbs during the forward lunge, with the trail limb generally experiencing greater total joint stress. Restricting forward translation of the lead-limb shank may reduce patellofemoral joint stress at the expense of increased stress in the trail limb. Technique recommendations should consider the demands imposed on both knees during this exercise. J Orthop Sports Phys Ther 2017;47(1):31-40. Epub 4 Nov 2016. doi:10.2519/jospt.2017.6336.

Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment.

Osteoarthritis (OA) is a progressive, degenerative disease of articulating joints that not only affects the elderly, but also involves younger, more active individuals with prolonged participation in high physical-demand activities. Thus, effective therapies that are easy to adopt clinically are critical in limiting the societal burden associated with OA. This review is focused on intra-articular injectable regimens and provides a comprehensive look at existing in vivo models of OA that might be suitable for developing, testing, and finding a cure for OA by intra-articular injections. We first discuss the pathology, molecular mechanisms responsible for the initiation and progression of OA, and challenges associated with disease-specific targeting of OA. We proceed to discuss available animal models of OA and provide a detailed perspective on the use of mouse models in studies of experimental OA. We finally provide a closer look at intra-articular injectable treatments for OA, focusing on biomaterials-based nanoparticles, and provide a comprehensive overview of the various nanometer-size ranges studied.