In vivo six‐degree‐of‐freedom knee‐joint kinematics in overground and treadmill walking following total knee arthroplasty

No data are available to describe six‐degree‐of‐freedom (6‐DOF) knee‐joint kinematics for one complete cycle of overground walking following total knee arthroplasty (TKA). The aims of this study were firstly, to measure 6‐DOF knee‐joint kinematics and condylar motion for overground walking following TKA; and secondly, to determine whether such data differed between overground and treadmill gait when participants walked at the same speed during both tasks. A unique mobile biplane X‐ray imaging system enabled accurate measurement of 6‐DOF TKA knee kinematics during overground walking by simultaneously tracking and imaging the joint. The largest rotations occurred for flexion‐extension and internal‐external rotation whereas the largest translations were associated with joint distraction and anterior‐posterior drawer. Strong associations were found between flexion‐extension and adduction‐abduction (R ² = 0.92), joint distraction (R ² = 1.00), and anterior‐posterior translation (R ² = 0.77), providing evidence of kinematic coupling in the TKA knee. Although the measured kinematic profiles for overground walking were grossly similar to those for treadmill walking, several statistically significant differences were observed between the two conditions with respect to temporo‐spatial parameters, 6‐DOF knee‐joint kinematics, and condylar contact locations and sliding. Thus, caution is advised when making recommendations regarding knee implant performance based on treadmill‐measured knee‐joint kinematic data. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1634–1643, 2017.

     

Influence of the anti‐inflammatory cytokine interleukin‐4 on human joint capsule myofibroblasts

Post‐traumatic joint contracture was reported to be associated with elevated numbers of contractile myofibroblasts (MFs) in the healing capsule. During the physiological healing process, the number of MFs declines; however, in fibroconnective disorders, MFs persist. The manifold interaction of the cytokines regulating the appearance and persistence of MFs in the pathogenesis of joint contracture remains to be elucidated. The objective of our current study was to analyze the impact of the anti‐inflammatory cytokine interleukin (IL)‐4 on functional behavior of MFs. Cells were isolated from human joint capsule specimens and challenged with three different concentrations of IL‐4 with or without its neutralizing antibody. MF viability, contractile properties, and the gene expression of both alpha‐smooth muscle actin (α‐SMA) and collagen type I were examined. Immunofluorescence staining revealed the presence of IL‐4 receptor (R)‐alpha (α) on the membrane of cultured MFs. The cytokine IL‐4 promoted MF viability and enhanced MF modulated contraction of collagen gels. Moreover, IL‐4 intervened in gene expression by up‐regulation of α‐SMA and collagen type I mRNA. These effects could be specifically lowered by the neutralizing IL‐4 antibody. On the basis of our findings we conclude that the anti‐inflammatory cytokine IL‐4 specifically regulates viability and the contractile properties of MFs via up‐regulating the gene expression of α‐SMA and collagen type I. IL‐4 may be a helpful target in developing anti‐fibrotic therapeutics for post‐traumatic joint contracture in human. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1290–1298, 2017.

     

Transoral atlantoaxial reduction plate internal fixation for the treatment of irreducible atlantoaxial dislocation: a 2‐ to 4‐year follow‐up

Objective: To evaluate the mid‐term outcomes of transoral atlantoaxial reduction plate (TARP) internal fixation for the treatment of irreducible atlantoaxial dislocation. Methods: From April 2003 to April 2005, 31 patients with irreducible atlantoaxial dislocation were treated with TARP internal fixation. The average age was 37.9 years (range, 15–69 years). The subjective symptoms, objective signs, and neurological function of the patients were assessed. Radiography and magnetic resonance imaging (MRI) were performed and the results analyzed according to the Symon and Lavender clinical standard, Japanese Orthopaedic Association (JOA) score for spinal cord function and imaging standard for spinal cord decompression. Results: Complete or almost complete anatomical reduction was obtained in all 31 patients. No screw‐loosening or atlantoaxial redislocation was found in 29 cases. According to the Symon and Lavender clinical standard, 14 cases had recovered completely, 7 to mild, 6 to moderate, and 4 to severe type by final follow‐up, compared to the preoperative classifications of 4 as moderate, 15 as severe, and 12 as extra severe type. The outcome for 26 patients was evaluated as excellent and in 5 as adequate. The average postoperative improvement in spinal cord function was 73.3% and of decompression of the cervical cord 92.6%. The only complication was loosening of screws in two cases with senile osteoporosis. One case underwent TARP revision surgery and the other posterior occipitocervical internal fixation. Both of them were eventually cured. Conclusion: The TARP operation is a good choice for patients with irreducible atlantoaxial dislocation and has valuable clinical application.     

Bi‐criteria optimal control of redundant robot manipulators using LVI‐based primal‐dual neural network

In this paper, a bi‐criteria weighting scheme is proposed for the optimal motion control of redundant robot manipulators. To diminish the discontinuity phenomenon of pure infinity‐norm velocity minimization (INVM) scheme, the proposed bi‐criteria redundancy‐resolution scheme combines the minimum kinetic energy scheme and the INVM scheme via a weighting factor. Joint physical limits such as joint limits and joint‐velocity limits could also be incorporated simultaneously into the scheme formulation. The optimal kinematic control scheme can be reformulated finally as a quadratic programming (QP) problem. As the real‐time QP solver, a primal‐dual neural network (PDNN) based on linear variational inequalities (LVI) is developed as well with a simple piecewise‐linear structure and global exponential convergence to optimal solutions. Since the LVI‐based PDNN is matrix‐inversion free, it has higher computational efficiency in comparison with dual neural networks. Computer simulations performed based on the PUMA560 manipulator illustrate the validity and advantages of such a bi‐criteria neural optimal motion‐control scheme for redundant robots. Copyright © 2009 John Wiley & Sons, Ltd.     

Predicting three‐dimensional patellofemoral kinematics from static imaging‐based alignment measures

Patellofemoral pain syndrome causes significant discomfort and disability among much of the general population. Despite recent breakthroughs in dynamic three‐dimensional imaging technologies to assess pathological patellofemoral motion, such tools remain costly for clinical diagnostics applications. Thus, this study investigated whether three‐dimensional patellofemoral kinematics could be predicted from routine two‐dimensional static measures of patellofemoral joint alignment quantified from magnetic resonance imaging (MRI) data acquired in full knee extension. Twenty‐six volunteers clinically diagnosed with patellofemoral pain (19 F/7 M, 25.9 ± 11.1 years) and 26 control subjects (19 F/7 M, 25.3 ± 7.7 years) were included in this IRB‐approved study. Static three‐dimensional sagittal T1‐weighted gradient recall echo and dynamic MRI scans were acquired. For the dynamic image acquisition, subjects cyclically flexed and extended their knee (at 30 cycles/min) while a full cine‐phase contrast MRI set (24 time frames of anatomic images and x‐, y‐, and z‐velocity images) was acquired. From these data, static measures of patellofemoral alignment and three‐dimensional patellofemoral kinematics were derived. Single and multiple regressions between static and kinematic variables were evaluated. Although shown reliable, the static MRI measures could only partially predict patellofemoral kinematics, with r²‐values ranging from 16% to 77%. This makes it imperitave that the current precise, accurate, 3D, dynamic imaging techniques be translated into clinical tools. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 441–447, 2013     

A time‐varying coefficient‐based manipulability‐maximizing scheme for motion control of redundant robots subject to varying joint‐velocity limits

A time‐varying coefficient‐based manipulability‐maximizing (TVCMM) scheme subject to varying joint‐velocity limits (VJVL) is proposed and investigated in this paper for the optimal motion control of redundant robot manipulators (where a planar robot manipulator is specifically considered). In order to improve the manipulability during the end‐effector task execution, a manipulability‐maximizing index is considered into the scheme formulation. Besides, for the remedy of the nonzero initial/final joint‐velocity problem, a time‐varying coefficient is introduced and incorporated in the scheme, which is further reformulated as a quadratic program (QP) subject to equality and bound constraints. For guaranteeing the physical realizability of such a scheme, an efficient linear variational inequality‐based (LVI‐based) numerical algorithm is employed to solve such a QP, and an experiment based on a 6‐DOF manipulator is presented, of which the redundancy is on the horizontal plane. Simulative and experimental results validate the physical realization, effectiveness, and accuracy of the proposed QP‐based manipulability‐maximizing scheme. Copyright © 2012 John Wiley & Sons, Ltd.     

Joint control for flexible‐joint robot with input‐estimation approach and LQG method

In this work, the input‐estimation (IE) algorithm and the linear quadratic Gaussian (LQG) controller are adopted to design a control system. The combined method can maintain higher control performance even when the system variation is unknown and under the influence of disturbance input. The IE algorithm is an on‐line inverse estimation method involving the Kalman filter (KF) and the least‐square method, which can estimate the system input without additional torque sensor, while the LQG control theory has the characteristic of low sensitivity of disturbance. The design and analysis processes of the controller will also be discussed in this paper. The joint control of the flexible‐joint robot system is utilized to test and verify the effectiveness of the control performance. According to the simulation results, the IE algorithm is an effective observer for estimating the disturbance torque input, and the LQG controller can effectively cope with the situation that the disturbance exists. Finally, higher control performance of the combined method for joint control of the robotic system can be further verified. Copyright © 2007 John Wiley & Sons, Ltd.     

Cytokine Interferon‐γ suppresses the function of capsule myofibroblasts and induces cell apoptosis

Myofibroblasts (MFs), a contractile subset of fibroblasts, play a pivotal role in physiological wound healing and in the development of many fibroconnective disorders. The complex cytokine network regulating the function of MFs in joint stiffness is still poorly understood. In this in vitro study, we investigated the effect of the cytokine Interferon‐gamma (IFN‐γ) on MFs isolated from human joint capsules. MFs were cultivated either in the presence of increasing concentrations of IFN‐γ alone or in combination with IFN‐γ neutralizing antibodies. Cell viability, cytotoxicity, apoptosis, and mRNA gene expression of the MF markers alpha‐smooth muscle actin (α‐SMA) and collagen type I were analyzed in MF cultures. Contraction potential was analyzed in an established collagen gel contraction assay simulating the extracellular matrix. Using immunofluorescence staining, we could verify that MFs express IFN‐γ‐receptor (R)‐1 on their membrane. IFN‐γ decreased MF viability and significantly elevated the apoptosis rate in a dose‐dependent manner. IFN‐γ down‐regulated α‐SMA and collagen type I mRNA expression which was associated with a diminished MF mediated contraction of the gel matrices. These effects were suppressed by simultaneous treatment of cells with a neutralizing IFN‐γ antibody. Our experiments confirm the hypothesis that the cytokine IFN‐γ is a crucial component of the regulatory network of capsule MFs. IFN‐γ notably influences the ability of MFs to contract collagen matrices by suppressing α‐SMA gene expression. IFN‐γ is toxic for MFs in high concentrations and may negatively regulate the number of pro‐fibrotic MFs during the healing process via induction of cell apoptosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2524–2533, 2017.

     

Comparison of synovial fluid,urine, and serum ion levels in metal‐on‐metal total hip arthroplasty at a minimum follow‐up of 18 years

Diagnosis of adverse reactions to metal debris in metal‐on‐metal hip arthroplasty is a multifactorial process. Systemic ion levels are just one factor in the evaluation and should not be relied upon solely to determine the need for revision surgery. Furthermore, the correlation between cobalt or chromium serum, urine, or synovial fluid levels and adverse local tissue reactions is still incompletely understood. The hypothesis was that elevated serum and urine metal‐ion concentrations are associated with elevated local metal‐ion concentrations in primary total hip arthroplasties (THA) and with failure of metal‐on‐metal articulations in the long‐term. In our present study, we evaluated these concentrations in 105 cementless THA with metal‐on‐metal articulating surfaces with small head diameter at a minimum of 18 years postoperatively. Spearman correlation showed a high correlation between the joint fluid aspirate concentration of cobalt and chromium with the serum cobalt (r = 0.81) and chromium level (r = 0.77) in patients with the THA as the only source of metal‐ions. In these patients serum metal‐ion analysis is a valuable method for screening. In patients with more than one source of metal or renal insufficiency additional investigations, like joint aspirations are an important tool for evaluation of wear and adverse tissue reactions in metal‐on‐metal THA. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1234–1240, 2014.     

Effect of gradual weight‐bearing on regenerated articular cartilage after joint distraction and motion in a rabbit model

The purpose of this study was to clarify the effect of gradual weight bearing (GWB) on regenerating cartilage. We developed a novel external fixation device (EFD) with a controllable weight‐bearing system and continuous passive motion (CPM). A full‐thickness defect was created by resection of the entire articular surface of the tibial plateau after the EFD was fixed in the rabbit's left knee. In the GWB group (n = 6), GWB was started 6 weeks after surgery. In the CPM group (n = 6), CPM with EFD was applied in the same manner without GWB. The control group (n = 5) received only joint distraction. All rabbits were sacrificed 9 weeks after surgery. The central one‐third of the regenerated tissue was assessed and scored blindly using a grading scale modified from the International Cartilage Repair Society visual histological assessment scale. The areas stained by Safranin‐O and type II collagen antibody were measured, and the percentage of each area was calculated. There was no significant difference in the histological assessment scale among the groups. The percentage of the type II collagen‐positive area was significantly larger in the GWB group than in the CPM group. The present study suggests that optimal mechanical stress, such as GWB, may affect regeneration of cartilage, in vivo. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:600–606, 2010     

Excellent Clinical Outcomes From a National Donation‐After‐Determination‐of‐Cardiac‐Death Lung Transplant Collaborative

Donation‐after‐Determination‐of‐Cardiac‐Death (DDCD) donor lungs can potentially increase the pool of lungs available for Lung Transplantation (LTx). This paper presents the 5‐year results for Maastricht category III DDCD LTx undertaken by the multicenter Australian National DDCD LTx Collaborative. The Collaborative was developed to facilitate interaction with the Australian Organ Donation Authority, standardization of definitions, guidelines, education and audit processes. Between 2006 and 2011 there were 174 actual DDCD category III donors (with an additional 37 potentially suitable donors who did not arrest in the mandated 90 min postwithdrawal window), of whom 71 donated lungs for 70 bilateral LTx and two single LTx. In 2010 this equated to an “extra” 28% of donors utilized for LTx. Withdrawal to pulmonary arterial flush was a mean of 35.2 ± 4.0 min (range 18–89). At 24 h, the incidence of grade 3 primary graft dysfunction was 8.5%[median PaO₂/FiO₂ ratio 315 (range 50–507)]. Overall the incidence of grade 3 chronic rejections was 5%. One‐ and 5‐year actuarial survival was 97% and 90%, versus 90% and 61%, respectively, for 503 contemporaneous brain‐dead donor lung transplants. Category III DDCD LTx therefore provides a significant, practical, additional quality source of transplantable lungs.     

Novel protein therapeutic joint retention strategy based on collagen‐binding Avimers

Designing drugs to treat diseases associated with articular joints, particularly those targeting chondrocytes, is challenging due to unique local environmental constraints including the avascular nature of cartilage, the absence of a closed joint compartment, and a highly cross‐linked extracellular matrix. In an effort to address these challenges, we developed a novel strategy to prolong residence time of intra‐articularly administered protein therapeutics. Avimer domains are naturally found in membrane polypeptides and mediate diverse protein–protein interactions. Screening of a phage Avimer domain library led to identification of several low affinity type II collagen‐binding Avimers. Following several rounds of mutagenesis and reselection, these initial hits were transformed to high affinity, selective type II collagen‐binding Avimers. One such Avimer (M26) persisted in rat knees for at least 1 month following intra‐articular administration. Fusion of this Avimer to a candidate therapeutic payload, IL‐1Ra, yielded a protein construct which simultaneously bound to type II collagen and to IL‐1 receptor. In vitro, IL‐1Ra_M26 bound selectively to cartilage explants and remained associated even after extensive washing. Binding appeared to occur preferentially to pericellular regions surrounding chondrocytes. An acute intra‐articular IL‐1‐induced IL‐6 challenge rat model was employed to assess in vivo pharmacodynamics. Whereas both IL‐1Ra_M26 and native IL‐1Ra inhibited IL‐6 output when co‐administered with the IL‐1 challenge, only IL‐1Ra_M26 inhibited when administered 1 week prior to IL‐1 challenge. Collagen‐binding Avimers thus represent a promising strategy for enhancing cartilage residence time of protein therapeutics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1238–1247, 2018.

     

Comparison of loading rate‐dependent injury modes in a murine model of post‐traumatic osteoarthritis

Post‐traumatic osteoarthritis (PTOA) is a common long‐term consequence of joint injuries such as anterior cruciate ligament (ACL) rupture. In this study we used a tibial compression overload mouse model to compare knee injury induced at low speed (1 mm/s), which creates an avulsion fracture, to injury induced at high speed (500 mm/s), which induces midsubstance tear of the ACL. Mice were sacrificed at 0 days, 10 days, 12 weeks, or 16 weeks post‐injury, and joints were analyzed with micro‐computed tomography, whole joint histology, and biomechanical laxity testing. Knee injury with both injury modes caused considerable trabecular bone loss by 10 days post‐injury, with the Low Speed Injury group (avulsion) exhibiting a greater amount of bone loss than the High Speed Injury group (midsubstance tear). Immediately after injury, both injury modes resulted in greater than twofold increases in total AP joint laxity relative to control knees. By 12 and 16 weeks post‐injury, total AP laxity was restored to uninjured control values, possibly due to knee stabilization via osteophyte formation. This model presents an opportunity to explore fundamental questions regarding the role of bone turnover in PTOA, and the findings of this study support a biomechanical mechanism of osteophyte formation following injury. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:79–88, 2014.     

Toll‐like receptors and their adaptors are regulated in macrophages after phagocytosis of lipopolysaccharide‐coated titanium particles

Macrophages phagocytose metallic wear particles and produce mediators, which can induce cellular host response and aseptic implant loosening. Lipopolysaccharide (LPS) on the wear debris can stimulate macrophages via Toll‐like receptor 4 (TLR4) and enhance the response. However, the precise functional role and interaction of TLRs and their adaptor molecules is still unclear. Rat bone marrow macrophages were stimulated with titanium particle (Ti) coated by LPS (Ti/LPS+) and LPS‐free Ti (Ti/LPS?). mRNA levels of cytokines, TLRs and their adaptor molecules were measured using real time PCR. mRNA levels of TNF‐α, IL‐1β, and IL‐6 increased in Ti/LPS+ than Ti/LPS?. In contrast, mRNA levels of TLR4, TLR5, and TLR9 decreased in Ti/LPS+ compared to Ti/LPS?. mRNA levels of MyD88, IRAK1, IRAK4 decreased gradually, and TRAF6 underwent an initial transient increase, followed by suppression in Ti/LPS+. However, mRNA levels of TLR2 and IRAK2 increased after phagocytosis of Ti/LPS+ than Ti/LPS?. The increased expressions of proinflammatory cytokines found in Ti/LPS+ indicated that their productions cytokines could be enhanced by phagocytosis of LPS‐coated particles. Subsequent down‐regulation of TLR4, TLR5, TLR9, MyD88, IRAK1, and IRAK4 suggests that self‐protective mechanisms to regulate excessive host responses are activated in macrophages. Increase of TLR2 and IRAK2 and a transient increase of TRAF6 in Ti/LPS+ suggest that another possible pathway to modulate TLR‐mediated cellular response to prolong inflammatory response in foreign body reaction of aseptic loosening. This down‐ and/or up‐regulation of the potential TLR‐mediated responses to LPS‐coated particles reflects the proactive behavior of effector cells. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 984–992, 2011