Understanding the long-term effects of total knee arthroplasty (TKA) on joint kinematics is vital to assess the success of the implant design and surgical procedure. However, while in vitro cadaveric studies quantifying post-operative biomechanics primarily reflect joint behaviour immediately after surgery,¹in vivo studies comprising of follow-up TKA patients often reflect joint behaviour a few months after surgery.² Therefore, the aim of this cadaveric study was to explore the long-term effects of TKA on tibiofemoral kinematics of a donor specimen, who had already undergone bilateral TKA, and compare them to post-operative kinematics reported in the literature.

Two fresh-frozen lower limbs from a single donor (male, age: 83yr, ht: 1.83m, wt: 86kg), who had undergone bilateral TKA (Genesis II, Smith&Nephew, Memphis, USA) 19 years prior to his demise, were obtained following ethical approval from the KU Leuven institutional board. The specimens were imaged using computed tomography (CT) and tested in a validated knee simulator³ replicating active squatting and varus-valgus laxity tests. Tibiofemoral kinematics were recorded using an optical motion capture system and compared to various studies in the literature using the same implant – experimental studies based on cadaveric specimens (CAD)^1,4 and an artificial specimen (ART)⁵, and a computational study (COM)⁶.

Maximum tibial abduction during laxity tests for the left leg (3.54°) was comparable to CAD (3.30°), while the right leg exhibited much larger joint laxity (8.52°). Both specimens exhibited valgus throughout squatting (left=2.03±0.57°, right=5.81±0.19°), with the change in tibial abduction over the range of flexion (left=1.89°, right=0.64°) comparable to literature (CAD=1.28°, COM=2.43°). The left leg was externally rotated (8.00±0.69°), while the right leg internally rotated (−15.35±1.50°), throughout squatting, with the change in tibial rotation over the range of flexion (left=2.61°, right=4.79°) comparable to literature (CAD=5.52°, COM=4.15°). Change in the femoral anteroposterior translation over the range of flexion during squatting for both specimens (left=14.88mm, right=6.76mm) was also comparable to literature (ART=13.40mm, COM=20.20mm).

Although TKA was reportedly performed at the same time on both legs of the donor by the same surgeon, there was a stark difference in their post-operative joint kinematics. A larger extent of intraoperative collateral ligament release could be one of the potential reasons for higher post-operative joint laxity in the right leg. Relative changes in post-operative tibiofemoral kinematics over the range of squatting were similar to those reported in the literature. However, differences between absolute magnitudes of joint kinematics obtained in this study and findings from the literature could be attributed to different surgeons performing TKA, with presumable variations in alignment techniques and/or patient specific instrumentation, and the slightly dissimilar ranges of knee flexion during squatting.

In conclusion, long-term kinematic effects of TKA quantified using in vitro testing were largely similar to the immediate post-operative kinematics reported in the literature; however, variation in the behaviour of two legs from the same donor suggested that intraoperative surgical alterations might have a greater effect on joint kinematics over time.

Orthopaedic training sessions, vital for surgeons to understand post-operative joint function, are primarily based on passive and subjective joint assessment. However, cadaveric knee simulators, commonly used in orthopaedic research,¹ could potentially benefit surgical training by providing quantitative joint assessment for active functional motions. The integration of cadaveric simulators in orthopaedic training was explored with recipients of the European Knee Society Arthroplasty Travelling Fellowship visiting our institution in 2018 and 2019. The aim of the study was to introduce the fellows to the knee joint simulator to quantify the surgeon-specific impact of total knee arthroplasty (TKA) on the dynamic joint behaviour, thereby identifying potential correlations between surgical competence and post-operative biomechanical parameters.

Eight fellows were assigned a fresh-frozen lower limb each to plan and perform posterior-stabilised TKA using MRI-based patient-specific instrumentation. Surgical competence was adjudged using the Objective Structured Assessment of Technical Skills (OSATS) adapted for TKA.² All fellows participated in the in vitro specimen testing on a validated knee simulator,³ which included motor tasks – passive flexion (0°-120°) and active squatting (35°-100°) – and varus-valgus laxity tests, in both the native and post-operative conditions. Tibiofemoral kinematics were recorded with an optical motion capture system and compared between native and post-operative conditions using a linear mixed model (p<0.05). The Pearson correlation test was used to assess the relationship between the OSATS scores for each surgeon and post-operative joint kinematics of the corresponding specimen (p<0.05).

OSATS scores ranged from 79.6% to 100% (mean=93.1, SD=7.7). A negative correlation was observed between surgical competence and change in post-operative tibial kinematics over the entire range of motion during passive flexion – OSATS score vs. change in tibial abduction (r=−0.87; p=0.003), OSATS score vs. change in tibial rotation (r=−0.76; p=0.02). When compared to the native condition, post-operative tibial internal rotation was higher during passive flexion (p<0.05), but lower during squatting (p<0.033). Post-operative joint stiffness was greater in extension than in flexion, without any correlation with surgical competence.

Although trained at different institutions, all fellows followed certain standard intraoperative guidelines during TKA, such as achieving neutral tibial abduction and avoiding internal tibial rotation,⁴ albeit at a static knee flexion angle. However, post-operative joint kinematics for dynamic motions revealed a strong correlation with surgical competence, i.e. kinematic variability over the range of passive flexion post-TKA was lower for more skilful surgeons. Moreover, actively loaded motions exhibited stark differences in post-operative kinematics as compared to those observed in passive motions. In vitro testing on the knee simulator also introduced the fellows to new quantitative parameters for post-operative joint assessment.

In conclusion, the inclusion of cadaveric simulators replicating functional joint motions could help quantify training paradigms, thereby enhancing traditional orthopaedic training, as was also the unanimous opinion of all participating fellows in their positive feedback.

Patients with osteoarthritis (OA) of the knee commonly alter their movement to compensate for deficiencies. This study presents a new numerical procedure for classifying sit-to-walk (STW) movement strategies.

Ten control and twelve OA participants performed the STW task in a motion capture laboratory. A full body biomechanical model was used. Participants were instructed to sit in a comfortable self-selected position on a stool height adjusted to 100% of their knee height and then stand and pick up an object from a table in front of them. Three matrices were constructed defining the progression of the torso, feet and hands in the sagittal plane along with a fourth expressing the location of the hands relative to the knees. Hierarchical clustering (HC) was used to identify different strategies. Trials were also classified as to whether the left (L) and right (R) extremities used a matching strategy (bilateral) or not (asymmetrical). Fisher's exact test was used to compare this between groups.

Clustering of the torso matrix dichotomised the trials in two major clusters; subjects leaning forward (LF) or not. The feet and hands matrices revealed sliding the foot backward (FB) and moving an arm forward (AF) strategies respectively. Trials not belonging in the AF cluster were submitted to the last HC of the fourth matrix exposing three additional strategies, the arm pushing through chair (PC), arm pushing through knee (PK) and arm not used (NA). The control participants used the LF+FBR+PK combination most frequently whereas the OA participants used the AFR+PCL. OA patients used significantly more asymmetrical arm strategies, p=0.034.

The results demonstrated that control and OA participants favour different STW strategies. The OA patients asymmetrical arm behaviour possibly indicates compensating for weakness of the affected leg. These strategy definitions may be useful to assess post-operative outcomes and rehabilitation progress.

Objectives

The aim of this study was to examine whether asymmetric loading influences macrophage elastase (MMP12) expression in different parts of a rat tail intervertebral disc and growth plate and if MMP12 expression is correlated with the severity of the deformity.

Introduction

Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily of growth factors and are known to regulate proliferation and expression of the differentiated phenotype of chondrocytes, osteoblasts, and osteoclasts. To investigate the osteoblastic differentiation gene expressions that contribute to BMP-7 dependent ostogenesis, we performed gene expression profiling of BMP-7-treated mouse bone marrow stromal cells.

This study compared the effect of a computer-assisted and a traditional surgical technique on the kinematics of the glenohumeral joint during passive abduction after hemiarthroplasty of the shoulder for the treatment of fractures. We used seven pairs of fresh-frozen cadaver shoulders to create simulated four-part fractures of the proximal humerus, which were then reconstructed with hemiarthroplasty and reattachment of the tuberosities. The specimens were randomised, so that one from each pair was repaired using the computer-assisted technique, whereas a traditional hemiarthroplasty without navigation was performed in the contralateral shoulder. Kinematic data were obtained using an electromagnetic tracking device.

The traditional technique resulted in posterior and inferior translation of the humeral head. No statistical differences were observed before or after computer-assisted surgery.

Although it requires further improvement, the computer-assisted approach appears to allow glenohumeral kinematics to more closely replicate those of the native joint, potentially improving the function of the shoulder and extending the longevity of the prosthesis.

We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle.

We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence.

Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches.

The pathogenesis of aseptic loosening of total joint prostheses is not clearly understood. Two features are associated with loosened prostheses, namely, particulate debris and movement of the implant. While numerous studies have evaluated the cellular response to particulate biomaterials, few have investigated the influence of movement of the implant on the biological response to particles. Our aim was therefore to test the hypothesis that excessive mechanical stimulation of the periprosthetic tissues induces an inflammatory response and that the addition of particulate biomaterials intensifies this.

We allocated 66 adult Beagle dogs to four groups as follows: stable implants with (I) and without (II) particulate polymethylmethacrylate (PMMA) and moving implants with (III) and without (IV) particulate PMMA. They were then evaluated at 2, 4, 6, 12 and 24 weeks.

The stable implants were well tolerated and a thin, fibrous membrane of connective tissue was observed. There was evidence of positive staining in some cells for interleukin-6 (IL-6). Addition of particulate PMMA around the stable implants resulted in an increase in the fibroblastic response and positive staining for IL-6 and tumour necrosis factor-alpha (TNF-α). By contrast, movement of the implant resulted in an immediate inflammatory response characterised by large numbers of histiocytes and cytokine staining for IL-1ß, TNF-α and IL-6. Introduction of particulate PMMA aggravated this response. Animals with particulate PMMA and movement of the implant have an intense inflammatory response associated with accelerated bone loss.

Our results indicate that the initiation of the inflammatory response to biomaterial particles was much slower than that to gross mechanical instability. Furthermore, when there was both particulate debris and movement, there was an amplification of the adverse tissue response as evidenced by the presence of osteolysis and increases in the presence of inflammatory cells and their associated cytokines.

Caveolae, specialised regions of the cell membrane which have been detected in a wide range of mammalian cells, have not been described in bone cells. They are plasmalemmal invaginations, 50 to 100 nm in size, characterised by the presence of the structural protein, caveolin, which exists as three subtypes. Caveolin-1 and caveolin-2 are expressed in a wide range of cell types whereas caveolin-3 is thought to be a muscle-specific subtype. There is little information on the precise function of caveolae, but it has been proposed that they play an important role in signal transduction.

As the principal bone-producing cell, the osteoblast has been widely studied in an effort to understand the signalling pathways by which it responds to extracellular stimuli. Our aim in this study was to identify caveolae and their structural protein caveolin in normal human osteoblasts, and to determine which subtypes of caveolin were present. Confocal microscopy showed staining which was associated with the plasma membrane. Transmission electron microscopy revealed the presence of membrane invaginations of 50 to 100 nm, consistent with the appearance of caveolae. Finally, we isolated protein from these osteoblasts, and performed Western blotting using anti-caveolin primary antibodies. This revealed the presence of caveolin-1 and -2, while caveolin-3 was absent.

The identification of these structures and their associated protein may provide a significant contribution to our further understanding of signal transduction pathways in osteoblasts.

We studied the effect of the surface finish of the stem on the transfer of load in the proximal femur in a sheep model of cemented hip arthroplasty. Strain-gauge analysis and corresponding finite-element (FE) analysis were performed to assess the effect of friction and creep at the cement-stem interface.

No difference was seen between the matt and polished stems. FE analysis showed that the effects of cement creep and friction at the stem-cement interface on femoral strain were small compared with the effect of inserting a cemented stem.

We examined macroscopically and microscopically 55 cadaver rotator-cuff tendons attached to their humeral heads to determine the distance between the edge of the articular cartilage and the tendon insertion of the supraspinatus (the width of the sulcus) and the score of regressive changes at the sulcus. In 33 specimens we measured the tensile strength. The width of the sulcus was correlated with the score of regressive changes and with the ultimate tensile strength of the supraspinatus tendon.

The width of the sulcus correlated positively with the score of regressive changes (r = 0.66, p < 0.0001), but there was a negative correlation between the latter and the ultimate tensile strength (r = −0.81, p = 0.001) and between the width of the sulcus and the ultimate tensile strength (r = −0.74, p = 0.004).

We believe that the width of the sulcus is a simple and useful clinical indicator of the integrity and the tensile strength of the supraspinatus tendon.

Posterior fixation of intervertebral discs is used to treat, and occasionally diagnose, discogenic pain since it is thought that it will reduce the internal loading of the discs in vitro. We measured the internal loading of ten intervertebral discs using stress profilometry under simulated physiological loads and then after posterior fixation. Partial discectomies were performed to simulate advanced disc degeneration and the sequence repeated.

Posterior fixation had very little effect on the magnitude of the loads acting on the disc and none when disc degeneration was simulated. It did, however, reduce bulging of the anterior annulus under combined bending and compression (p < 0.03). Recent experiments in vivo have shown that discogenic pain is associated with abnormal bulging of the annulus which suggests that the clinical benefit of fixation may be due to this.

We investigated the distribution of compressive ‘stress’ within cadaver intervertebral discs, using a pressure transducer mounted in a 1.3 mm diameter needle. The needle was pulled along the midsagittal diameter of a lumbar disc with the face of the transducer either vertical or horizontal while the disc was subjected to a constant compressive force. The resulting ‘stress profiles’ were analysed in order to characterise the distribution of vertical and horizontal compressive stress within each disc. A total of 87 discs from subjects aged between 16 and 87 years was examined.

Our results showed that age-related degenerative changes reduced the diameter of the central hydrostatic region of each disc (the ‘functional nucleus’) by approximately 50%, and the pressure within this region fell by 30%. The width of the functional annulus increased by 80% and the height of compressive ‘stress peaks’ within it by 160%. The effects of age and degeneration were greater at L4/L5 than at L2/L3, and the posterior annulus was affected more than the anterior. Age and degeneration were themselves closely related, but the stage of degeneration had the greater effect on stress distributions.

We suggest that structural changes within the annulus and endplate lead to a transfer of load from the nucleus to the posterior annulus. High ‘stress’ concentrations within the annulus may cause pain, and lead to further disruption.