Aims

To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

Background

Undisplaced Lisfranc-type injuries are subtle but potentially unstable fracture-dislocations with little known about the natural history. These injuries are often initially managed conservatively due to lack of initial displacement and uncertainty regarding subsequent instability at the tarsometatarsal joints (TMTJ). The aim of this study was to determine the secondary displacement rate and the need for delayed operative intervention in undisplaced Lisfranc injuries that were managed conservatively at initial presentation.

Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery.

Tendinopathy is the most frequent musculoskeletal disease that requires medical attention. Mechanical overload has been considered as a key driver of its pathology. However, the underline mechanism on how overload induces tendinopathy and inflammation is unclear. Extracellular mitochondria (EM) are newly identified as cell-to-cell communicators. The aim of this study is to elucidate the role of mitochondria in overload-induced inflammation.

We performed three-dimensional uniaxial stretching to mouse tendon organoid in bioreactors. Cyclic strain of uniaxial loadings included underload, normal load, and overload, according to previous work. We then harvested microvesicles including EM, from the bioreactor by differential centrifugation and evaluated their characteristics by flow cytometry and super-resolution confocal microscopy. Raw 264.7 mouse macrophage cell line was used for chemotaxis assay in a Boyden Chamber System with Magnetic-Activated Cell Sorting Technology. EM induced cytokines secretion by macrophages was analyzed by a bead-based multiplex assay panel. N-Acetyl-L-cysteine (NAC) was used as the antioxidant to tendon organoid to regulate mitochondrial fitness.

We showed mechanical load induced tendon organoid to release microvesicles including mitochondria. The size of microvesicles is mainly in the range from 220nm to 880nm. More than 75% of microvesicles could be stained by PKH26, confirming they were with lipophilic membrane. Super-resolution confocal microscopy identified two forms of mitochondria, including mitochondria encapsulated in vesicles and free mitochondria. Overload led to the degeneration of the organoid and induced microvesicles release containing most EM. Chemotaxis assay showed that EM from overloaded tendon organoid induced macrophages chemotaxis. In addition, microvesicles extracted from overloaded tendon organoid induced the production of proinflammatory cytokines including IL-6, KC (Keratinocyte-Derived Chemokine) and IL-18. NAC treatment to tendon cells could attenuate overload-induced macrophage chemotaxis.

Overload induces EM releasing from tendon cells, which leads to chemotaxis of macrophages toward tendon, resulting in induction of inflammation.

To determine the risk of total knee replacement (TKR) for primary osteoarthritis (OA) associated with overweight/obesity in the Australian population.

This population-based study analyzed 191,723 cases of TKR collected by the Australian Orthopaedic Association National Joint Registry and population data from the Australian Bureau of Statistics. The time-trend change in incidence of TKR relating to BMI was assessed between 2015-2018. The influence of obesity on the incidence of TKR in different age and gender groups was determined. The population attributable fraction (PAF) was then calculated to estimate the effect of obesity reduction on TKR incidence.

The greatest increase in incidence of TKR was seen in patients from obese class III. The incidence rate ratio for having a TKR for obesity class III was 28.683 at those aged 18-54 years but was 2.029 at those aged >75 years. Females in obesity class III were 1.7 times more likely to undergo TKR compared to similarly classified males. The PAFs of TKR associated with overweight or obesity was 35%, estimating 12,156 cases of TKR attributable to obesity in 2018. The proportion of TKRs could be reduced by 20% if overweight and obese population move down one category.

Obesity has resulted in a significant increase in the incidence of TKR in the youngest population in Australia. The impact of obesity is greatest in the young and the female population. Effective strategies to reduce the national obese population could potentially reduce 35% of the TKR, with over 10,000 cases being avoided.

To address the current challenge of anterior cruciate ligament (ACL) reconstruction, this study is the first to fabricate a braided collagen rope (BCR) which mimics native hamstring for ACL reconstruction. The study aims to evaluate the biological and biomechanical properties of BCR both in vivo and vitro.

Rabbit ACL reconstruction model using collagen rope and autograft (hamstring tendon) was conducted. The histological and biomechanical evaluations were conducted at 6-, 12-, 18, 26-week post-operation. In vitro study included cell morphology analysis, cell function evaluation and RNA sequencing of the tenocytes cultured on BCR. A cadaver study was also conducted to verify the feasibility of BCR for ACL reconstruction.

BCR displays satisfactory mechanical strength similar to hamstring graft for ACL reconstruction in rabbit. Histological assessment showed BCR restore ACL morphology at 26 weeks similar to native ACL. The superior dynamic ligamentization in BCR over autograft group was evidenced by assessment of cell and collagen morphology and orientation. The in vitro study showed that the natural collagen fibres within BCR enables to signal the morphology adaptation and orientation of human tenocytes in bioreactor. BCR enables to enhance cell proliferation and tenogenic expression of tenocytes as compared to hydrolysed collagen. We performed an RNA-Sequencing (RNA-seq) experiment where RNA was extracted from tenocyte seeded with BCR. Analysis of enriched pathways of the up-regulated genes revealed that the most enriched pathways were the Hypoxia-inducible factor 1-alpha (HIF1A) regulated networks, implicating the possible mechanism BCR induced ACL regeneration. The subsequent cadaver study was conducted to proof the feasibility of BCR for ACL reconstruction.

This study demonstrated the proof-of-concept of bio-textile braided collagen rope for ACL reconstruction, and the mechanism by which BCR induces natural collagen fibres that positively regulate morphology and function of tenocytes.

Open reduction and internal fixation (ORIF) with trans-articular screws or dorsal plating is the standard surgical technique for displaced Lisfranc injuries. This aim of this study is to compare the clinical outcomes of percutaneous reduction and internal fixation (PRIF) of low energy Lisfranc injuries with a matched, control group of patients treated with ORIF.

Over a seven-year period (2012–2019), 16 consecutive patients with a low energy Myerson B2-type injury were treated with PRIF. Patient demographics were recorded within a prospectively maintained database at the institution. This study sample was matched for age, sex and mechanism of injury to a control group of 16 patients with similar Myerson B2-type injuries treated with ORIF. Clinical outcome was compared using the American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score and Manchester Oxford Foot Questionnaire (MOXFQ).

At a mean follow up of 43.0 months (95% CI 35.6 – 50.4), both the AOFAS and MOXFQ scores were significantly higher in the PRIF group compared to the control ORIF group (AOFAS 89.1vs 76.4, p=0.03; MOXFQ 10.0 vs 27.6, p=0.03). There were no immediate postoperative complications in either group. At final follow up, there was no radiological evidence of midfoot osteoarthritis in any patient in the PRIF group. Three patients in the ORIF group developed midfoot osteoarthritis, one of whom required midfoot fusion.

PRIF is a technically simple, less invasive method of operative stabilisation of low energy Lisfranc injures which also appears to be associated with better mid-term clinical outcomes compared to ORIF.

Aims

The aim of this study was to define the complications and long-term outcome following adolescent mid-shaft clavicular fracture.

Objectives

Platelet-rich fibrin matrix (PRFM) has been proved to enhance tenocyte proliferation but has mixed results when used during rotator cuff repair. The optimal PRFM preparation protocol should be determined before clinical application. To screen the best PRFM to each individual’s tenocytes effectively, small-diameter culture wells should be used to increase variables. The gelling effect of PRFM will occur when small-diameter culture wells are used. A co-culture device should be designed to avoid this effect.

Background:

Little is known about the forces carried by the Taylor Spatial Frame (TSF) hexapod fixator. Our aim was to measure the TSF resultant force and how this changed during the consolidation phase.

Introduction:

Microseparation has resulted in more than ten-fold increase in ceramic-on-ceramic and metal-on-metal bearing wear, and even fracture in a zirconia head [1–4]. However, despite the greater microseparation reported clinically for metal-on-polyethylene wear, less is known about its potential detrimental effects for this bearing couple. This study was therefore designed to simulate the effects of micromotion using finite element analysis and to validate computational predictions with experimental wear testing.

It is difficult to determine the safe timing of weight-bearing or reconstructive surgery in patients with Charcot arthropathy of the foot and ankle. In this study the Doppler spectrum of the first dorsal metatarsal artery was used to monitor the activity of the disease activity and served as a guideline for management. A total of 15 patients (seven men and eight women) with acute diabetic Charcot arthropathy of the foot and ankle were immobilised in a non-weight-bearing cast. They were followed at two-week intervals and bilateral Doppler spectra of the first dorsal metatarsal arteries were obtained using a 10 MHz linear ultrasound probe. The patients were allowed to start weight-bearing or undergo surgery after the Doppler spectrum had returned to normal pattern. The Doppler spectra in the unaffected limbs were triphasic in pattern, whereas those in limbs with active Charcot arthropathy showed monophasic forward flow. They returned to normal after a mean of 13.6 weeks (6 to 20) of immobilisation. Three patients underwent pan-talar arthrodesis to correct gross instability and deformity.

Doppler spectrum analysis of the foot may reflect the activity of the disease in patients with Charcot arthropathy, and may be used as a guide to begin weight-bearing or undergo reconstructive surgery.

Patellofemoral complications are among the important reasons for revision knee arthroplasty. Femoral component malposition has been implicated in patellofemoral maltracking, which is associated with anterior knee pain, subluxation, fracture, wear, and aseptic loosening. Rotating-platform mobile bearings compensate for malrotation between the tibial and femoral components. It has been suggested that rotating bearings may also reduce the patellofemoral maltracking resulting from femoral component malposition.

We constructed a dynamic musculoskeletal model of weight-bearing knee flexion in a knee implanted with posterior cruciate-retaining arthroplasty components (LifeMOD/KneeSIM, LifeModeler Inc). The model was validated using tibiofemoral and patellofemoral kinematics and forces measured in cadaver knees on an Oxford knee rig. Knee kinematics and patellofemoral forces were measured after simulating axial malrotation of the femoral component (±3° of the transepicondylar reference line). Differences in patellofemoral kinematics and forces between the fixed- and rotating-bearing conditions were analysed.

Rotational malalignment of the femoral component affected tibial rotation near full extension and tibial adduction at higher flexion angles. In the fixed-bearing conditions, external rotation of the femoral component increased patellofemoral lateral tilt, patellofemoral lateral shift, and patellofemoral lateral shear forces. Up to 6° of bearing rotation relative to the tibia was noted in the rotating-bearing condition. However, the rotating bearing had minimal effect in reducing the patellofemoral maltracking or shear induced by femoral component rotation.

The rotating bearing does not appear to be forgiving of malalignment of the extensor mechanism resulting from femoral component malrotation. The rotating bearing may correct tibiofemoral axial malrotation near full extension but not at higher knee flexion angles. These results support the value of improving existing methodologies for accurate femoral component alignment in knee arthroplasty.

Introduction and Aims: Studies have shown substantial reduction in wear rates in elevated cross-linked polyethylene (crosslinking to a higher degree than that obtained by radiation sterilisation alone). The aim of this study was to test the effect of increased crosslinking and increased head size on polyethylene wear rates.

Method: Four groups of acetabular liners from a single manufacturer were tested: 28mm nominally cross-linked, 32mm nominally cross-linked, 28mm elevated cross-linked, and 32mm elevated cross-linked. Three implants from each group were tested in a 12-station hip wear simulator using 90% bovine serum as lubricant. Liners were articulated with the appropriately sized cobalt-chrome femoral head. Additional liners from each design were subjected only to the same load without motion to serve as load-soak controls to account for any weight gain due to fluid absorption. Gravimetric analysis was performed every 500,000 cycles for a total of 5,000,000 cycles.

Results: Nominally cross-linked liners demonstrated mean wear rates of 14.97±2.70 and 16.92±2.58 milligrams/million cycles for 28mm and 32mm head sizes, respectively. Both of the elevated cross-linked liners had significantly lower wear rates than controls with a mean of 1.51±1.08 and 2.57±1.78 milligrams/million cycles for 28mm and 32mm head sizes, respectively (p< 0.001).

Conclusion: Larger femoral head sizes reduce dislocation in total hip arthroplasty; however, they have been associated with unacceptably high wear rates. The dramatic reduction in wear rates with polyethylene crosslinking even with the larger head size may increase the potential for use of 32mm head components in total hip arthroplasty.

Polyethylene wear is a significant factor limiting survivorship of total knee arthroplasty (TKR). Crosslinking of polyethylene has been shown to significantly reduce wear in hip arthroplasty but has not been reported for TKR. This study measured wear in polyethylene cross-linked to two levels in a knee wear simulator.

Six polyethylene knee inserts were tested in a knee wear simulator. Inserts were manufactured from polyethylene crosslinked to two different levels: 2.5 Mrad (Low-X) and 10.5 Mrad (High-X). Each implant was enclosed in a closed lubricant (50% alpha fraction calf serum) recirculation chamber, maintained at 37°C and changed every 500,000 cycles. Physiologic levels of load and motion were applied at 1 Hz for a total of 6,000,000 cycles. Wear was measured by the gravimetric method before wear testing and at every 500,000 cycles. Semi-quantitative wear assessment was performed by imaging the insert surfaces at 10x magnification.

The Low-X inserts demonstrated significantly higher wear rates (mean 4.66 mg/million cycles) than the High-X inserts (mean 1.55 mg/million cycles, p < 0.001). Wear scars on the Low-X inserts were irregular and visibly deeper than those on the High-X inserts. The machining marks on the surface of the insert were also better preserved in the High-X insert wear scars. These results suggest that crosslinked PE can significantly reduce wear in TKR under physiologic conditions. This can result in reduced lysis and increased survivorship. Localized damage can cause catastrophic failure in polyethylene knee inserts. Therefore, further studies are necessary to evaluate wear under these conditions.

Polyethylene contact stresses have been shown to correlate with wear in total hip arthroplasty (THA). Several liner designs have been introduced in an attempt to increase stability or reduce impingement and increase range of motion. This study analyzed the effect of liner design on range of motion (ROM) and PE contact stresses in a finite element model (FEM).

FEMs of four liner designs were generated: Generic was modelled as a simple hemisphere, Chamfer had a wide chamfer on the inner edge of the liner to increase ROM, Highwall had an extended lip to increase stability, and Anteverted created a 20° anteversion with lat-eralisation of the centre of rotation. With the liners in varying positions of abduction and anteversion, physiologic loads were applied through the femoral head. Hip ROM was measured by rotating the head and neck in different directions until prosthetic impingement.

Significant differences in ROM were seen relative to the Generic liner. Chamfer increased ROM by mean 16%. Highwall reduced ROM by mean 12%. Anteverted increased flexion by 17% but decreased extension, abduction, and external rotation. Contact stresses were also significantly affected by liner design and acetabular orientation. Overall for the same acetabular position, contact stresses were higher for Chamfer and lower for Highwall and Anteverted.

These results underline the complex interaction between cup design, hip stability, range of motion and contact stresses. Design features that increase stability tend to reduce contact stresses and ROM, while those features that increase ROM, tend to increase contact stresses. This data can help the surgeon match liner design to specific patient requirements.

This study measured polyethylene wear and correlated it with design features such as tibiofemoral conformity and contact areas.

Two femoral component designs were tested in a knee wear simulator. The femoral condyles of design A were flat-on-flat in the coronal plane, while those of design B were curved-on-curved. These femoral components were tested with two inserts. Insert PLI had a posterior lip, while insert C had a more curved sagital geometry, to improve stability in the anteroposterior direction. All components were tested for up to five million cycles in bovine serum lubricant. Triaxial forces were monitored to ensure that loading conditions were similar in all combinations tested. Gravimetric wear measurements were made at 500 000 cycle intervals. Contact stresses were measured using pressure sensitive film and dynamic finite element analysis.

Contact stresses were 22% higher for inserts tested with design A compared to design B. Sliding distance, sliding velocity, and patterns of crossing motion were found to be comparable between the two femoral designs. Inserts tested with design A wore significantly more (mean 10.9 mg/million cycles) than design B (mean 5.71 mg/million cycles, p < 0.001). No appreciable differences were found between wear rates of insert PLI and insert C.

Component design can have a significant impact on polyethylene wear rate. Careful control of kinematic and loading conditions allowed for comparison between specific design features. Increase in tibio-femoral contact area led to reduction of contact stresses, which was reflected in the reduced wear rate.

There is quite a high incidence of musculoskeletal disorders in the hemophiliac patients because of their insufficiency in blood coagulation. Knee joint disability is the most troublesome problem among the all. Repeated bruise and intra-articular hemorrhage may activate hypertrophic synovitis and progress to advanced arthritis. The characteristic clinical presentation is their fusiform limbs with moderate degree of contracture and deformity. Treatments include administration of specific coagulation factors, aspiration of hemarthrosis and proper bracing. Synovectomy will treat and retard the progression of the disease, while some advanced cases may end up to spontaneous fusion or need surgical arthrodesis. Total knee arthroplasty is another option for such a knee problem in hemophiliac patients.

We have done 26 total knee arthroplasties in 19 hemophiliac patients since 1986. Male is predominant with sex-linked inheritance with only one exception. The timing for them to have surgery is from 22 to 47 years old with mean age of 30. Gross patholgies of the knee lesion are quite universal as hypertrophy of hemosiderin deposited synovium, destruction of articular catilage, subchondral bone loss, marginal osteophytes formation, fibrous contracture around the joints. Two cases were excluded for other systemic disease.

With the help of supplementary coagulation factor, the surgical courses were rather smooth with one exception of septic shock episode. There were no infections in total series but three revisions of prosthesis were done because of loosening or malposition. All the patients were satisfied with the improvement of function score and range of knee motion. Total knee arthroplasty did a great success for the relief of pain and function for such a knee disorder. The only remained troublesome problem is the extremely high cost of the coagulation factor therapy which may be an economic shock to the patients.