A MOVING CONTACT OF ARTICULATION ENHANCES THE BIOSYNTHETIC AND FUNCTIONAL RESPONSES OF ARTICULAR CARTILAGE.

Biomechanical influences play a fundamental role in the structural, functional, and biosynthetic properties of articular cartilage. During physiologic joint loading, the contact area between two surfaces migrates due to the primary and secondary motions of the joint. It has been demonstrated that a migratory contact area plays a critical role in reducing the coefficient of friction at the cartilage surface. However, a detailed analysis of the influences that a migratory contact area plays on the structural, functional, and biosynthetic properties remain to be explored. In this study, bovine cartilage explants were placed in a biotribometer. Explants were subjected to compression and shear forces of migratory contact area, namely moving contact (MC) articulation, or stationary contact area, namely stationary contact (SC) articulation. Free swelling explants were used as control. In a separate study, bovine cartilage-bone grafts were used for frictional testing. On histologic analysis, the SC group had evidence of surface fibrillations, which was not evident in the MC group. Compared to the SC group, the MC group cartilage explants had increased chondrocyte viability, increased lubricin synthesis, and comparable proteoglycan synthesis and release. MC articulation had reduced coefficient of friction as compared to SC articulation. MC articulation led to reduced surface roughness as compared to SC articulation. In conclusion, a migratory contact area can play an important role in maintaining the structural, function, and biosynthetic properties of articular cartilage. This study provides further evidence of the importance of migratory contact area and in vitro assessment of natural joint movement, which can be further evaluated in the context of cartilage homeostasis and disease.

ESTABLISHING A LIVE CARTILAGE-ON-CARTILAGE INTERFACE FOR TRIBOLOGICAL TESTING.

Mechano-biochemical wear encompasses the tribological interplay between biological and mechanical mechanisms responsible for cartilage wear and degradation. The aim of this study was to develop and start validating a novel tribological testing system, which better resembles the natural joint environment through incorporating a live cartilage-on-cartilage articulating interface, joint specific kinematics, and the application of controlled mechanical stimuli for the measurement of biological responses in order to study the mechano-biochemical wear of cartilage. The study entailed two parts. In Part 1, the novel testing rig was used to compare two bearing systems: (a) cartilage articulating against cartilage (CoC) and (b) metal articulating against cartilage (MoC). The clinically relevant MoC, which is also a common tribological interface for evaluating cartilage wear, should produce more wear to agree with clinical observations. In Part II, the novel testing system was used to determine how wear is affected by tissue viability in live and dead CoC articulations. For both parts, bovine cartilage explants were harvested and tribologically tested for three consecutive days. Wear was defined as release of glycosaminoglycans into the media and as evaluation of the tissue structure. For Part I, we found that the live CoC articulation did not cause damage to the cartilage, to the extent of being comparable to the free swelling controls, whereas the MoC articulation caused decreased cell viability, extracellular matrix disruption, and increased wear when compared to CoC, and consistent with clinical data. These results provided confidence that this novel testing system will be adequate to screen new biomaterials for articulation against cartilage, such as in hemiarthroplasty. For Part II, the live and dead cartilage articulation yielded similar wear as determined by the release of proteoglycans and aggrecan fragments, suggesting that keeping the cartilage alive may not be essential for short term wear tests. However, the biosynthesis of glycosaminoglycans was significantly higher due to live CoC articulation than due to the corresponding live free swelling controls, indicating that articulation stimulated cell activity. Moving forward, the cell response to mechanical stimuli and the underlying mechano-biochemical wear mechanisms need to be further studied for a complete picture of tissue degradation.

Development of a Cartilage Shear-Damage Model to Investigate the Impact of Surface Injury on Chondrocytes and Extracellular Matrix Wear.

Background Many i n vitro damage models investigate progression of cartilage degradation after a supraphysiologic, compressive impact at the surface and do not model shear-induced damage processes. Models also neglect the response to uninterrupted tribological stress after damage. It was hypothesized that shear-induced removal of the superficial zone would accelerate matrix degradation when damage was followed by continued load and articulation. Methods Bovine cartilage underwent a 5-day test. Shear-damaged samples experienced 2 days of damage induction with articulation against polyethylene and then continued articulation against cartilage (CoC), articulation against metal (MoC), or rest as free-swelling control (FSC). Surface-intact samples were randomized to CoC, MoC, or FSC for the entire 5-day test. Samples were evaluated for chondrocyte viability, GAG (glycosaminoglycan) release (matrix wear surrogate), and histological integrity. Results Shear induction wore away the superficial zone. Damaged samples began continued articulation with collagen matrix disruption and increased cell death compared to intact samples. In spite of the damaged surface, these samples did not exhibit higher GAG release than intact samples articulating against the same counterface ( P = 0.782), contrary to our hypothesis. Differences in GAG release were found to be due to tribological testing against metal ( P = 0.003). Conclusion Shear-induced damage lowers chondrocyte viability and affects extracellular matrix integrity. Continued motion of either cartilage or metal against damaged surfaces did not increase wear compared with intact samples. We conjecture that favorable reorganization of the surface collagen fibers during articulation protected the underlying matrix. This finding suggests a potential window for clinical interventions to slow matrix degradation after traumatic incidents.

Implications of trauma and subsequent articulation on the release of Proteoglycan-4 and tissue response in adult human ankle cartilage.

The purpose of this study was to investigate the effects of trauma and subsequent articulation on adult human ankle cartilage subjected to an injurious impact. Trauma was initiated through impaction on talar cartilage explants. Articulation and loading were applied in a joint bioreactor over 5 consecutive days. The early (24 h) effects of impaction included a reduced chondrocytes viability (51% vs. 81% for non-impacted; p = 0.03), increased levels of apoptosis (43% vs. 27%; p = 0.03), and an increase in the histopathology score (4.4 vs. 1.7; p = 0.02) as compared to non-impacted cartilage explants. One of the key findings was that damage also stimulated the PRG4 release (2.2 vs. 1.5 µg/ml). Subsequent articulation for 5 days did not lead to further changes in tissue histopathology and cell viability, neither for injured nor non-injured samples. However, articulation led to an increased apoptosis in the injured samples (p = 0.03 for the interaction term). Articulation also caused a significant increase of PG/GAG release into the culture medium (p = 0.04) for both injured and non-injured samples; however, the synthesis of PG was not affected by articulation (p = 0.45) though the PG synthesis was higher in injured samples (p < 0.01). With regard to the PRG4 release, impacted samples continued to show higher amounts (p = 0.01), adding articulation led to a reduction (p = 0.02). The current study demonstrated that adult human talar cartilage increases both the PRG4 release and biosynthetic activity as an immediate cellular response to injury. Articulation played a less contributing role to biosynthesis and remodeling, behaving mostly neutral, in that no further damage emerged. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:667-676, 2017.

How have alternative bearings and modularity affected revision rates in total hip arthroplasty?

BACKGROUND: Total hip arthroplasty (THA) continues to be one of the most successful surgical procedures in the medical field. However, over the last two decades, the use of modularity and alternative bearings in THA has become routine. Given the known problems associated with hard-on-hard bearing couples, including taper failures with more modular stem designs, local and systemic effects from metal-on-metal bearings, and fractures with ceramic-on-ceramic bearings, it is not known whether in aggregate the survivorship of these implants is better or worse than the metal-on-polyethylene bearings that they sought to replace. QUESTIONS/PURPOSES: Have alternative bearings (metal-on-metal and ceramic-on-ceramic) and implant modularity decreased revision rates of primary THAs? METHODS: In this systematic review of MEDLINE and EMBASE, we used several Boolean search strings for each topic and surveyed national registry data from English-speaking countries. Clinical research (Level IV or higher) with ≥ 5 years of followup was included; retrieval studies and case reports were excluded. We included registry data at ≥ 7 years followup. A total of 32 studies (and five registry reports) on metal-on-metal, 19 studies (and five registry reports) on ceramic-on-ceramic, and 20 studies (and one registry report) on modular stem designs met inclusion criteria and were evaluated in detail. Insufficient data were available on metal-on-ceramic and ceramic-on-metal implants, and monoblock acetabular designs were evaluated in another recent systematic review so these were not evaluated here. RESULTS: There was no evidence in the literature that alternative bearings (either metal-on-metal or ceramic-on-ceramic) in THA have decreased revision rates. Registry data, however, showed that large head metal-on-metal implants have lower 7- to 10-year survivorship than do standard bearings. In THA, modular exchangeable femoral neck implants had a lower 10-year survival rate in both literature reviews and in registry data compared with combined registry primary THA implant survivorship. CONCLUSIONS: Despite improvements in implant technology, there is no evidence that alternative bearings or modularity have resulted in decreased THA revision rates after 5 years. In fact, both large head metal-on-metal THA and added modularity may well lower survivorship and should only be used in select cases in which the mission cannot be achieved without it. Based on this experience, followup and/or postmarket surveillance studies should have a duration of at least 5 years before introducing new alternative bearings or modularity on a widespread scale.

The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes.

OBJECTIVE: Although growth factor therapy could be an attractive method for stimulating the repair of damaged cartilage matrix, there is evidence that with aging and/or with the development of osteoarthritis (OA), articular chondrocytes may become unresponsive to growth factor stimulation. The aim of the current study was to compare the ability of insulin-like growth factor+(IGF-1) and osteogenic protein+(OP-1), alone and in combination, to stimulate human normal and OA chondrocytes in culture. METHODS: Chondrocytes isolated by enzymatic digestion of cartilage obtained from subjects undergoing knee replacement for OA (n = 6) or from normal ankle joints of tissue donors (n = 7) were cultured in alginate beads in serum-free medium and treated for 21 days with 100 ng/ml IGF-1, 100 ng/ml OP-1, or both. Controls were treated with vehicle alone. The cultures were evaluated for cell survival, cell number by DNA analysis, matrix production by particle exclusion assay, and level of accumulated proteoglycan by dimethylmethylene blue assay. RESULTS: After 21 days in serum-free alginate culture, survival of cells from OA cartilage was 65 +/- 2% (mean +/- SEM), while survival of cells from normal cartilage was significantly greater (82 +/- 3%). Treatment with either IGF-1 or OP-1 alone minimally improved survival, while the combination IGF +OP significantly improved survival, to 87 +/- 2% for OA cells and 95+/-1% for normal cells. Cell proliferation was noted only in the IGF+OP group; this was significant for both normal and OA cells ( approximately 2-fold increase in DNA levels). Matrix production, assessed by particle exclusion and by proteoglycan accumulation, was greatest in the cells treated with IGF + OP in both normal and OA cultures. When proteoglycan levels were corrected for cell numbers (mg proteoglycan/ng DNA), a significant increase over control was noted with OP-1 alone and IGF IGF-1 alone, in both normal and OA cultures, with the greatest levels in the combination group (3-fold increase over control). CONCLUSION: OP-1 was more potent than IGF-1 in stimulating proteoglycan production in both normal and OA cells. However, the best results were obtained with the combination, suggesting that combined therapy with IGF-1 and OP-1 may be an effective strategy for treating OA cartilage damage.