Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Objectives

Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes.

Objectives

Preservation of both anterior and posterior cruciate ligaments in total knee arthroplasty (TKA) can lead to near-normal post-operative joint mechanics and improved knee function. We hypothesised that a patient-specific bicruciate-retaining prosthesis preserves near-normal kinematics better than standard off-the-shelf posterior cruciate-retaining and bicruciate-retaining prostheses in TKA.

Objectives

Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis.

We evaluated two reconstruction techniques for a simulated posterolateral corner injury on ten pairs of cadaver knees. Specimens were mounted at 30° and 90° of knee flexion to record external rotation and varus movement. Instability was created by transversely sectioning the lateral collateral ligament at its midpoint and the popliteus tendon was released at the lateral femoral condyle. The left knee was randomly assigned for reconstruction using either a combined or fibula-based treatment with the right knee receiving the other. After sectioning, laxity increased in all the specimens. Each technique restored external rotatory and varus stability at both flexion angles to levels similar to the intact condition. For the fibula-based reconstruction method, varus laxity at 30° of knee flexion did not differ from the intact state, but was significantly less than after the combined method. Both the fibula-based and combined posterolateral reconstruction techniques are equally effective in restoring stability following the simulated injury

There has been only one limited report dating from 1941 using dissection which has described the tibiofemoral joint between 120° and 160° of flexion despite the relevance of this arc to total knee replacement. We now provide a full description having examined one living and eight cadaver knees using MRI, dissection and previously published cryosections in one knee. In the range of flexion from 120° to 160° the flexion facet centre of the medial femoral condyle moves back 5 mm and rises up on to the posterior horn of the medial meniscus. At 160° the posterior horn is compressed in a synovial recess between the femoral cortex and the tibia. This limits flexion. The lateral femoral condyle also rolls back with the posterior horn of the lateral meniscus moving with the condyle. Both move down over the posterior tibia at 160° of flexion. Neither the events between 120° and 160° nor the anatomy at 160° could result from a continuation of the kinematics up to 120°. Therefore hyperflexion is a separate arc. The anatomical and functional features of this arc suggest that it would be difficult to design an implant for total knee replacement giving physiological movement from 0° to 160°

We evaluated the histological changes before and after fixation in ten knees of ten patients with osteochondritis dissecans who had undergone fixation of the unstable lesions. There were seven males and three females with a mean age of 15 years (11 to 22). The procedure was performed either using bio-absorbable pins only or in combination with an autologous osteochondral plug. A needle biopsy was done at the time of fixation and at the time of a second-look arthroscopy at a mean of 7.8 months (6 to 9) after surgery.

The biopsy specimens at the second-look arthroscopy showed significant improvement in the histological grading score compared with the pre-fixation scores (p < 0.01). In the specimens at the second-look arthroscopy, the extracellular matrix was stained more densely than at the time of fixation, especially in the middle to deep layers of the articular cartilage.

Our findings show that articular cartilage regenerates after fixation of an unstable lesion in osteochondritis dissecans.

The understanding of rotational alignment of the distal femur is essential in total knee replacement to ensure that there is correct placement of the femoral component. Many reference axes have been described, but there is still disagreement about their value and mutual angular relationship. Our aim was to validate a geometrically-defined reference axis against which the surface-derived axes could be compared in the axial plane. A total of 12 cadaver specimens underwent CT after rigid fixation of optical tracking devices to the femur and the tibia. Three-dimensional reconstructions were made to determine the anatomical surface points and geometrical references. The spatial relationships between the femur and tibia in full extension and in 90° of flexion were examined by an optical infrared tracking system.

After co-ordinate transformation of the described anatomical points and geometrical references, the projection of the relevant axes in the axial plane of the femur were mathematically achieved. Inter- and intra-observer variability in the three-dimensional CT reconstructions revealed angular errors ranging from 0.16° to 1.15° for all axes except for the trochlear axis which had an interobserver error of 2°. With the knees in full extension, the femoral transverse axis, connecting the centres of the best matching spheres of the femoral condyles, almost coincided with the tibial transverse axis (mean difference −0.8°, sd 2.05). At 90° of flexion, this femoral transverse axis was orthogonal to the tibial mechanical axis (mean difference −0.77°, sd 4.08). Of all the surface-derived axes, the surgical transepicondylar axis had the closest relationship to the femoral transverse axis after projection on to the axial plane of the femur (mean difference 0.21°, sd 1.77). The posterior condylar line was the most consistent axis (range −2.96° to −0.28°, sd 0.77) and the trochlear anteroposterior axis the least consistent axis (range −10.62° to +11.67°, sd 6.12). The orientation of both the posterior condylar line and the trochlear anteroposterior axis (p = 0.001) showed a trend towards internal rotation with valgus coronal alignment.

Carbonate-substituted hydroxyapatite (CHA) is more osteoconductive and more resorbable than hydroxyapatite (HA), but the underlying mode of its action is unclear. We hypothesised that increased resorption of the ceramic by osteoclasts might subsequently upregulate osteoblasts by a coupling mechanism, and sought to test this in a large animal model. Defects were created in both the lateral femoral condyles of 12 adult sheep. Six were implanted with CHA granules bilaterally, and six with HA. Six of the animals in each group received the bisphosphonate zoledronate (0.05 mg/kg), which inhibits the function of osteoclasts, intra-operatively. After six weeks bony ingrowth was greater in the CHA implants than in HA, but not in the animals given zoledronate. Functional osteoclasts are necessary for the enhanced osteoconduction seen in CHA compared with HA

We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 μg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks.

The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022).

The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament.

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells.

Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation.

We investigated several factors which affect the stability of cortical screws in osteoporotic bone using 18 femora from cadavers of women aged between 45 and 96 years (mean 76). We performed bone densitometry to measure the bone mineral density of the cortical and cancellous bone of the shaft and head of the femur, respectively. The thickness and overall bone mass of the cortical layer of the shaft of the femur were measured using a microCT scanner. The force required to pull-out a 3.5 mm titanium cortical bone screw was determined after standardised insertion into specimens of the cortex of the femoral shaft.

A significant correlation was found between the pull-out strength and the overall bone mass of the cortical layer (r² = 0.867, p < 0.01) and also between its thickness (r² = 0.826, p < 0.01) and bone mineral density (r² = 0.861, p < 0.01). There was no statistically significant correlation between the age of the donor and the pull-out force (p = 0.246), the cortical thickness (p = 0.199), the bone mineral density (p = 0.697) or the level of osteoporosis (p = 0.378).

We conclude that the overall bone mass, the thickness and the bone mineral density of the cortical layer, are the main factors which affect the stability of a screw in human female osteoporotic cortical bone.

We stably transfected early passage chondrocytes with an anti-apoptotic Bcl-2 gene in vitro using a retrovirus vector. Samples of articular cartilage were obtained from 11 patients with a mean age of 69 years (61 to 75) who were undergoing total knee replacement for osteoarthritis. The Bcl-2-gene-transfected chondrocytes were compared with non-transfected and lac-Z-gene-transfected chondrocytes, both of which were used as controls. All three groups of cultured chondrocytes were incubated with nitric oxide (NO) for ten days. Using the Trypan Blue exclusion assay, an enzyme-linked immunosorbent assay and flow cytometric analysis, we found that the number of apoptotic chondrocytes was significantly higher in the non-transfected and lac-Z-transfected groups than in the Bcl-2-transfected group (p < 0.05). The Bcl-2-transfected chondrocytes were protected from NO-induced impairment of proteoglycan synthesis.

We conclude that NO-induced chondrocyte death involves a mechanism which appears to be subject to regulation by an anti-apoptotic Bcl-2 gene. Therefore, Bcl-2 gene therapy may prove to be of therapeutic value in protecting human articular chondrocytes.

The weight-bearing status of articular cartilage has been shown to affect its biochemical composition. We have investigated the topographical variation of sulphated glycosaminoglycan (GAG) relative to the DNA content of the chondrocyte in human distal femoral articular cartilage.

Paired specimens of distal femoral articular cartilage, from weight-bearing and non-weight-bearing regions, were obtained from 13 patients undergoing above-knee amputation. After papain enzyme digestion, spectrophotometric GAG and fluorometric DNA assays assessed the biochemical composition of the samples. The results were analysed using a paired t-test.

Although there were no significant differences in cell density between the regions, the weight-bearing areas showed a significantly higher concentration of GAG relative to DNA when compared with non-weight-bearing areas (p = 0.02).

We conclude that chondrocytes are sensitive to their mechanical environment, and that local loading conditions influence the metabolism of the cells and hence the biochemical structure of the tissue.

We developed an in vivo model of the attachment of a patellar tendon to a metal implant to simulate the reconstruction of an extensor mechanism after replacement of the proximal tibia. In 24 ewes, the patellar tendon was attached to a hydroxyapatite (HA)-coated titanium prosthesis. In 12, the interface was augmented with autograft containing cancellous bone and marrow. In the remaining ewes, the interface was not grafted.

Kinematic gait analysis showed nearly normal function of the joint by 12 weeks. Force-plate assessment showed a significant increase in functional weight-bearing in the grafted animals (p = 0.043). The tendon-implant interface showed that without graft, encapsulation of fibrous tissue occurred. With autograft, a developing tendon-bone-HA-implant interface was observed at six weeks and by 12 weeks a layered tendon-fibrocartilage-bone interface was seen which was similar to a direct-type enthesis.

With stable mechanical fixation, an appropriate bioactive surface and biological augmentation the development of a functional tendon-implant interface can be achieved.

In this study a combination of autologous chondrocyte implantation (ACI) and the osteochondral autograft transfer system (OATS) was used and evaluated as a treatment option for the repair of large areas of degenerative articular cartilage. We present the results at three years post-operatively. Osteochondral cores were used to restore the contour of articular cartilage in 13 patients with large lesions of the lateral femoral condyle (n = 5), medial femoral condyle (n = 7) and patella (n = 1). Autologous cultured chondrocytes were injected underneath a periosteal patch covering the cores. After one year, the patients had a significant improvement in their symptoms and after three years this level of improvement was maintained in ten of the 13 patients. Arthroscopic examination revealed that the osteochondral cores became well integrated with the surrounding cartilage. We conclude that the hybrid ACI/OATS technique provides a promising surgical approach for the treatment of patients with large degenerative osteochondral defects

MRI studies of the knee were performed at intervals between full extension and 120° of flexion in six cadavers and also non-weight-bearing and weight-bearing in five volunteers. At each interval sagittal images were obtained through both compartments on which the position of the femoral condyle, identified by the centre of its posterior circular surface which is termed the flexion facet centre (FFC), and the point of closest approximation between the femoral and tibial subchondral plates, the contact point (CP), were identified relative to the posterior tibial cortex. The movements of the CP and FFC were essentially the same in the three groups but in all three the medial differed from the lateral compartment and the movement of the FFC differed from that of the CP. Medially from 30° to 120° the FFC and CP coincided and did not move anteroposteriorly. From 30° to 0° the anteroposterior position of the FFC remained unchanged but the CP moved forwards by about 15 mm. Laterally, the FFC and the CP moved backwards together by about 15 mm from 20° to 120°. From 20° to full extension both the FFC and CP moved forwards, but the latter moved more than the former. The differences between the movements of the FFC and the CP could be explained by the sagittal shapes of the bones, especially anteriorly. The term ‘roll-back’ can be applied to solid bodies, e.g. the condyles, but not to areas. The lateral femoral condyle does roll-back with flexion but the medial does not, i.e. the femur rotates externally around a medial centre. By contrast, both the medial and lateral contact points move back, roughly in parallel, from 0° to 120° but they cannot ‘roll’. Femoral roll-back with flexion, usually imagined as backward rolling of both condyles, does not occur

We studied active flexion from 90° to 133° and passive flexion to 162° using MRI in 20 unloaded knees in Japanese subjects. Flexion over this arc is accompanied by backward movement of the medial femoral condyle of 4.0 mm and by backward movement laterally of 15 mm, i.e., by internal rotation of the tibia. At 162° the lateral femoral condyle lies posterior to the tibia