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This study was designed to analyze the effects of type of activity and cruciate ligament resection on knee kinematics and ligament balance after total knee arthroplasty (TKA), and to determine if intraoperative passive kinematics are associated with active kinematics. Fresh‐frozen human cadaveric knees were examined. The knees were mounted on a quadriceps‐driven simulator. Cruciate‐retaining (CR‐TKA) and posterior‐substituting (PS‐TKA) TKA was performed using a contemporary knee system. Active flexion (closed‐kinetic chain [CKC] and open‐kinetic‐chain [OKC]) and passive flexion were analyzed by recording the knee kinematics using a specifically developed application of an imageless navigation system. An electronic ligament balancer was used to measure the tibiofemoral gap under constant distraction pressure. The femur rotated externally relative to the tibia during passive and active CKC flexion. The femur translated anteriorly from 10° to 50° of flexion after TKA. Beyond 50° of flexion, the femur translated posteriorly in all surgical conditions. The femoral location during active CKC flexion was posterior relative to that during active OKC. Femoral rotation and translation during passive knee flexion correlated significantly with that during active knee flexion. Posterior tilt of the electronic ligament balancer was greater with CR‐TKA than with PS‐TKA and correlated significantly with the anteroposterior position of the femur. Statement of Clinical Significance: Intraoperative knee kinematics measured by computer‐assisted navigation and intraoperative ligament balance have the potential to predict postoperative knee kinematics. [ABSTRACT FROM AUTHOR]

ABSTRACT: Avascular (Avas) meniscus regeneration remains a challenge, which is partly a consequence of our limited knowledge of the cells that maintain this tissue region. In this study, we utilized microarrays to characterize gene expression profiles of intact human Avas meniscus tissue and of cells following culture expansion. Using these data, we examined various 3D culture conditions to redifferentiate Avas cells toward the tissue phenotype. RNA was isolated from either the tissue directly or following cell isolation and 2 weeks in monolayer culture. RNA was hybridized on human genome arrays. Differentially expressed (DE) genes were identified by ranking analysis. DAVID pathway analysis was performed and visualized using STRING analysis. Quantitative PCR (qPCR) on additional donor menisci (tissues and cells) were used to validate array data. Avas cells cultured in 3D were subjected to qPCR to compare with the array‐generated data. A total of 387 genes were DE based on differentiation state (>3‐fold change; p < 0.01). In Avas‐cultured cells, the upregulated pathways included focal adhesion, ECM‐receptor interaction, regulation of actin cytoskeleton, and PDGF Signaling. In 3D‐cultured Avas cells, TGFβ1 or combinations of TGFβ1 and BMP6 were most effective to promote an Avas tissue phenotype. THBS2 and THBS4 expression levels were identified as a means to denote meniscus cell phenotype status. We identified the key gene expression profiles, new markers and pathways involved in characterizing the Avas meniscus phenotype in the native state and during in vitro dedifferentiation and redifferentiation. These data served to screen 3D conditions to generate meniscus‐like neotissues. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1947–1958, 2018. [ABSTRACT FROM AUTHOR]

Mechanical loading is believed to be a critical factor in the development and treatment of knee osteoarthritis. However, the contact forces to which the knee articular surfaces are subjected during daily activities cannot be measured clinically. Thus, the ability to predict internal knee contact forces accurately using external measures (i.e., external knee loads and muscle electromyographic [EMG] signals) would be clinically valuable. We quantified how well external knee load and EMG measures predict internal knee contact forces during gait. A single subject with a force-measuring tibial prosthesis and post-operative valgus alignment performed four gait patterns (normal, medial thrust, walking pole, and trunk sway) to induce a wide range of external and internal knee joint loads. Linear regression analyses were performed to assess how much of the variability in internal contact forces was accounted for by variability in the external measures. Though the different gait patterns successfully induced significant changes in the external and internal quantities, changes in external measures were generally weak indicators of changes in total, medial, and lateral contact force. Our results suggest that when total contact force may be changing, caution should be exercised when inferring changes in knee contact forces based on observed changes in external knee load and EMG measures. Advances in musculoskeletal modeling methods may be needed for accurate estimation of in vivo knee contact forces. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 921-929, 2013 [ABSTRACT FROM AUTHOR]

Persistent pain is an important cause of patient dissatisfaction after unicompartmental knee replacement (UKR) and has been correlated with localized tibial strain. However, the factors that influence these strains are not well understood. To address this issue, we created finite element models to examine the effect on tibial strain of: (1) muscle forces (estimated using instrumented knee data) acting on attachment sites on the proximal tibia, (2) UKR implantation, (3) loading position, and (4) changes in gait pattern. Muscle forces acting on the tibia had no significant influence on strains within the periprosthetic region, but UKR implantation increased strain by 20%. Strain also significantly increased if the region of load application was moved >3 mm medially. The strain within the periprosthetic region was found to be dependent on gait pattern and was influenced by both medial and lateral loads, with the medial load having a greater effect (regression coefficients: medial = 0.74, lateral = 0.30). These findings suggest that tibial strain is increased after UKR and may be a cause of pain. It may be possible to reduce pain through modification of surgical factors or through altered gait patterns. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 821-828, 2013 [ABSTRACT FROM AUTHOR]

Lower body positive pressure (LBPP) treadmills permit significant unweighting of patients and have the potential to enhance recovery following lower limb surgery. We determined the efficacy of an LBPP treadmill in reducing knee forces in vivo. Subjects, implanted with custom electronic tibial prostheses to measure forces in the knee, were tested on a treadmill housed within a LBPP chamber. Tibiofemoral forces were monitored at treadmill speeds from 1.5 mph (0.67 m/s) to 4.5 mph (2.01 m/s), treadmill incline from −10° to +10°, and four treadmill chamber pressure settings adjusted to decrease net treadmill reaction force from 100% to 25% of the subject's body weight (BW). The peak axial tibiofemoral force ranged from 5.1 times BW at a treadmill speed of 4.5 mph (2.01 m/s) and a pressure setting of 100% BW to 0.8 times BW at 1.5 mph (0.67 m/s) and a pressure setting of 25% BW. Peak knee forces were significantly correlated with walking speed and treadmill reaction force ( R2 = 0.77, p = 0.04). The LBPP treadmill might be an effective tool in the rehabilitation of patients following lower-extremity surgery. The strong correlation between tibiofemoral force and walking speed and treadmill reaction forces allows for more precisely achieving the target knee forces desired during early rehabilitation. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 672-679, 2013 [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (OA) commonly occurs in the medial compartment of the knee and has been linked to overloading of the medial articular cartilage. Gait modification represents a non-invasive treatment strategy for reducing medial compartment knee force. The purpose of this study was to evaluate the effectiveness of a variety of gait modifications that were expected to alter medial contact force. A single subject implanted with a force-measuring knee replacement walked using nine modified gait patterns, four of which involved different hiking pole configurations. Medial and lateral contact force at 25, 50, and 75% of stance phase, and the average value over all of stance phase (0-100%), were determined for each gait pattern. Changes in medial and lateral contact force values relative to the subject's normal gait pattern were determined by a Kruskal-Wallis test. Apart from early stance (25% of stance), medial contact force was most effectively reduced by walking with long hiking poles and wide pole placement, which significantly reduced medial and lateral contact force during stance phase by up to 34% (at 75% of stance) and 26% (at 50% of stance), respectively. Although this study is based on data from a single subject, the results provide important insight into changes in medial and lateral contact forces through gait modification. The results of this study suggest that an optimal configuration of bilateral hiking poles may significantly reduce both medial and lateral compartment knee forces in individuals with medial knee osteoarthritis. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 434-440, 2013 [ABSTRACT FROM AUTHOR]

Impairment of the human neuromusculoskeletal system can lead to significant mobility limitations and decreased quality of life. Computational models that accurately represent the musculoskeletal systems of individual patients could be used to explore different treatment options and optimize clinical outcome. The most significant barrier to model-based treatment design is validation of model-based estimates of in vivo contact and muscle forces. This paper introduces an annual 'Grand Challenge Competition to Predict In Vivo Knee Loads' based on a series of comprehensive publicly available in vivo data sets for evaluating musculoskeletal model predictions of contact and muscle forces in the knee. The data sets come from patients implanted with force-measuring tibial prostheses. Following a historical review of musculoskeletal modeling methods used for estimating knee muscle and contact forces, we describe the first two data sets used for the first two competitions and summarize four subsequent data sets to be used for future competitions. These data sets include tibial contact force, video motion, ground reaction, muscle EMG, muscle strength, static and dynamic imaging, and implant geometry data. Competition participants create musculoskeletal models to predict tibial contact forces without having access to the corresponding in vivo measurements. These blinded predictions provide an unbiased evaluation of the capabilities and limitations of musculoskeletal modeling methods. The paper concludes with a discussion of how these unique data sets can be used by the musculoskeletal modeling research community to improve the estimation of in vivo muscle and contact forces and ultimately to help make musculoskeletal models clinically useful. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:503-513, 2012 [ABSTRACT FROM AUTHOR]

Tibial tray malalignment has been associated with increased subsidence and failure. We constructed a finite element model of knee arthroplasty to determine the biomechanical factors involved in increasing the risk of subsidence with malalignment. Four fresh-frozen human knees were implanted with a tibial tray and subjected to forces representative of walking for up to 100,000 cycles. Cyclic displacement was measured between the tray and proximal tibia. The vertical load was shifted medially to generate a load distribution ratio of 55:45 (medial/lateral) to represent neutral alignment or 75:25 to represent varus alignment. Subjected specific geometry and material properties were obtained from qCT scans of tibia to construct a finite element model. The tray was subjected to a single load cycle representing experimental conditions. Tray displacement computed by the model matched that measured experimentally. Forces representing varus tray alignment generated greater strains in the proximal tibia and a greater volume of bone was subjected to strains higher than the fatigue threshold. Local compressive strains directly correlated with experimental subsidence and failure. Our results indicate that failure after tray malalignment is likely due to fatigue damage to the proximal tibia rather than shear across the implant-bone interface or failure of the cement mantle. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:347-353, 2011 [ABSTRACT FROM AUTHOR]

Actin and tubulin cytoskeletal components are studied extensively in chondrocytes, but less is known about vimentin intermediate filaments. In other cell types, vimentin is a determinant of cell stiffness and disruption of vimentin networks weakens the mechanical integrity of cells. Changes in vimentin organization correlate with osteoarthritis progression, but the functional consequences of these changes remain undetermined in chondrocytes. The objective of this study was to compare the contribution of vimentin to the mechanical stiffness of primary human chondrocytes isolated from normal versus osteoarthritic cartilage. Chondrocytes were embedded in alginate and vimentin networks disrupted with acrylamide. Constructs were imaged while subjected to 20% nominal strain on a confocal microscope stage, and the aspect ratios of approximately 1,900 cells were measured. Cytosolic stiffness was estimated with a finite element model, and live-cell imaging of GFP-vimentin was used to further analyze the nature of vimentin disruption. Vimentin in normal chondrocytes formed an inner cage-like network that was substantially stiffer than the rest of the cytosol and contributed significantly to overall cellular stiffness. Disruption of vimentin reduced stiffness approximately 2.8-fold in normal chondrocytes. In contrast, osteoarthritic chondrocytes were less stiff and less affected by vimentin disruption. This 3D experimental system revealed contributions of vimentin to chondrocyte stiffness previously not apparent, and correlated changes in vimentin-based chondrocyte stiffness with osteoarthritis. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:20-25, 2011 [ABSTRACT FROM AUTHOR]

Advances in cross-linking have led to the development of wear resistant ultrahigh molecular weight polyethylene for total joint replacement. This study compared wear reduction by two different cross-linking methods as measured in a hip wear simulator. One highly cross-linked polyethylene was treated with 7.5 Mrad gamma irradiation with post-irradiation annealing and a sterilization dose of 2.5 Mrad (10 Gamma), while the other used 9.5 Mrad warm irradiation with 10 MeV electron-beam (9.5 EB). Liners of the same design, made from nominally cross-linked (gamma sterilized) polyethylene were also tested. Gravimetric wear analysis was performed every 500,000 cycles for 5,000,000 cycles. After correcting for weight gain due to water absorption, the nominally cross-linked liners demonstrated mean wear rates of 15.7 (±1.7) and 12.5 (±1.0) mg/million cycles. Both highly cross-linked polyethylene liners demonstrated significantly less wear than their respective controls (with mean wear rates of 1.5 (±1.2) and −1.4 (±1.5) mg/million cycles). The 9.5 EB liners gained weight presumably due to increased fluid absorption, in addition to that measured in loaded–soaked control implants. Any wear occurring was therefore assumed to have been more than offset by weight gain. Highly cross-linked polyethylene was significantly more wear resistant than non- or nominally cross-linked polyethylene. The differences in wear rates between the two highly cross-linked polyethylene designs (9.5 EB or 10 Gamma) are probably too small to be clinically significant. [Copyright &y& Elsevier]