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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 64 - 64
22 Nov 2024
Mbuku RB Poilvache H Van Bambeke F Cornu O
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Aim. The management of PJIs is slowed down by the presence of bacteria forming biofilms where they may withstand antibiotic therapy. The use of adjuvant strategies, such as hydrolytic enzymes cocktail targeting biofilm matrices and facilitating their dispersion, is a promising option to limit impact of biofilms. Our aim was to evaluate the effect of enzymes cocktail combined with antibiotic dual therapy of rifampicin and vancomycin in a relevant in-vitro model. Method. Mature methicillin-resistant Staphylococcus aureus biofilms were grown on Ti-6Al-4V coupons by adding 1mL of a 8Log10 ATCC 33591 suspension in TGN (TSB + 1% glucose + 2% NaCl) to 24-wells plates containing the coupons and incubating the plates for 24h at 37°C with a continuous 50rpm agitation. The samples were rinsed and placed in 6 wells plates containing 1ml of the enzymatic cocktail (C.D.D.) solution (tris-buffered (pH 7.0) solution of 400 U/ml of aspecific DNA/RNA endonuclease, 50 U/ml of endo-1,4-b-D-glucanase, and 0.06 U/ml of β-N-acetylhexosaminidase). 9ml of TGN or TGN containing antibiotics RIF/VAN (rifampicin 5µg/mL + vancomycin 8µg/mL) at clinically relevant concentrations found locally in bone or joints, was then added and the samples were incubated in identical conditions for 24h. The samples were then recovered and rinsed. CFU counts were obtained by recovering the bacteria with sonication, serial dilutions, and TSA plating. Biomass was determined via crystal violet staining, followed by dye solubilization in acetic acid, and absorbance measurement using a spectrophotometer. Results. Significant reductions in bacterial counts were observed in biofilms exposed to either RIF/VAN or RIF/VAN+CDD, by respectively 2,6 and 3,7Log10 when compared to samples reincubated with TGN alone (p <0.05). Additionally, CFU counts in samples exposed to RIF/VAN+CDD were reduced by 1,1Log10 when compared to those exposed to RIF/VAN (p<0,05). Significant reduction in biomass (-29,8%, p<0.05) was observed for coupons exposed to RIF/VAN+CDD when compared to C.D.D alone (figure 1). Conclusions. The concurrent utilization of enzymes with rifampicin and vancomycin, holds promise as a feasible method to address periprosthetic joint infections (PJIs). For any tables or figures, please contact the authors directly


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 76 - 76
19 Aug 2024
Cook SD Patron LP Salkeld SL Nolan LP Lavernia CJ
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Dislocation after total hip replacement (THR) is a devastating complication. Risk factors include patient and surgical factors. Mitigation of this complication has proven partially effective. This study investigated a new innovating technique to decrease this problem using rare earth magnets. Computer simulations with design and magnetic finite element analysis software were used to analyze and quantitate the forces around hip implants with embedded magnets into the components during hip range of motion. N52 Neodymium-Iron-Boron rare earth magnets were sized to fit within the existing acetabular shells and the taper of a hip system. Additionally, magnets placed within the existing screw holes were studied. A 50mm titanium acetabular shell and a 36mm ceramic liner utilizing a taper sleeve adapter were modeled which allowed for the use of a 12mm × 5mm magnet placed in the center hole, an 18mm × 15mm magnet within the femoral head, and 10mm × 5mm magnets in the screw holes. Biomechanical testing was also performed using in-vitro bone and implant models to determine retention forces through a range of hip motion. The novel system incorporating magnets generated retentive forces between the acetabular cup and femoral head of between 10 to 20 N through a range of hip motion. Retentive forces were stronger at the extreme position hip range of motion when additional magnets were placed in the acetabular screw holes. Greater retentive forces can be obtained with specially designed femoral head bores and acetabular shells specifically designed to incorporate larger magnets. Mechanical testing validated the loads obtained and demonstrated the feasibility of the magnet system to provide joint stability and prevent dislocations. Rare earth magnets provide exceptional attractive strength and can be used to impart stability and prevent dislocation in THR without the complications and limitations of conventional methods


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 80 - 80
2 Jan 2024
Mischler D Windolf M Gueorguiev B Varga P
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Osteosynthesis aims to maintain fracture reduction until bone healing occurs, which is not achieved in case of mechanical fixation failure. One form of failure is plastic plate bending due to overloading, occurring in up to 17% of midshaft fracture cases and often necessitating reoperation. This study aimed to replicate in-vivo conditions in a cadaveric experiment and to validate a finite element (FE) simulation to predict plastic plate bending. Six cadaveric bones were used to replicate an established ovine tibial osteotomy model with locking plates in-vitro with two implant materials (titanium, steel) and three fracture gap sizes (30, 60, 80 mm). The constructs were tested monotonically until plastic plate deformation under axial compression. Specimen-specific FE models were created from CT images. Implant material properties were determined using uniaxial tensile testing of dog bone shaped samples. The experimental tests were replicated in the simulations. Stiffness, yield, and maximum loads were compared between the experiment and FE models. Implant material properties (Young's modulus and yield stress) for steel and titanium were 184 GPa and 875 MPa, and 105 GPa and 761 MPa, respectively. Yield and maximum loads of constructs ranged between 469–491 N and 652–683 N, and 759–995 N and 1252–1600 N for steel and titanium fixations, respectively. FE models accurately and quantitatively correctly predicted experimental results for stiffness (R2=0.96), yield (R2=0.97), and ultimate load (R2=0.97). FE simulations accurately predicted plastic plate bending in osteosynthesis constructs. Construct behavior was predominantly driven by the implant itself, highlighting the importance of modelling correct material properties of metal. The validated FE models could predict subject-specific load bearing capacity of osteosyntheses in vivo in preclinical or clinical studies. Acknowledgements: This study was supported by the AO Foundation via the AOTRAUMA Network (Grant No.: AR2021_03)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 125 - 125
2 Jan 2024
Mbuku R Sanchez C Evrard R Englebert A Manon J Henriet V Nolens G Duy K Schubert T Henrotin Y Cornu O
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To design slow resorption patient-specific bone graft whose properties of bone regeneration are increased by its geometry and composition and to assess it in in-vitro and in-vivo models. A graft composed by hydroxyapatite (HA) and β-TCP was designed as a cylinder with 3D gyroid porosities and 7 mm medullary space based on swine's anatomy. It was produced using a stereolithography 3D-printing machine (V6000, Prodways). Sterile bone grafts impregnated with or without a 10µg/mL porcine BMP-2 (pBMP-2) solution were implanted into porcine femurs in a bone loss model. Bone defect was bi-weekly evaluated by X-ray during 3 months. After sacrifice, microscanner and non-decalcified histology analysis were conducted on biopsies. Finally, osteoblasts were cultured inside the bone graft or in monolayer underneath the bone graft. Cell viability, proliferation, and gene expression were assessed after 7 and 14 days of cell culture (n=3 patients). 3D scaffolds were successfully manufactured with a composition of 80% HA and 20% β-TCP ±5% with indentation compressive strength of 4.14 MPa and bending strength of 11.8MPa. In vivo study showed that bone regeneration was highly improved in presence of pBMP-2. Micro-CT shows a filling of the gyroid sinuses of the implant (Figure 1). In vitro, the presence of BMP2 did not influence the viability of the osteoblasts and the mortality remained below 3%. After 7 days, the presence of BMP2 in the scaffold significantly increased by 85 and 65% the COL1A1 expression and by 8 and 33-fold the TNAP expression by osteoblasts in the monolayer or in the scaffold, respectively. This BMP2 effect was transient in monolayer and did not modify gene expression at day 14. BMP2-impregnated bone graft is a promising patient-personalized 3D-printed solution for bone defect regeneration, by promoting neighboring host cells recruitment and solid new bone formation. For any figures and tables, please contact the authors directly


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 130 - 130
2 Jan 2024
Dvorak N
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In-vitro models of disease are valuable tools for studying disease and analysing response to therapeutics. Recently, advances in patient-derived organoid (PDO) models have been shown to faithfully recapitulate structure, function, and therapeutic response for a wide range of tissues. Frozen shoulder is a rare example of a chronic inflammatory fibrotic disease which is self-limiting, unlike many other soft tissue fibrotic disorders. As no in-vitro 3D models or in-vivo animal models exist for frozen shoulder, establishing an organoid model which recapitulates core diseases features may give insight into fibrosis resolution. Consequently, using biocompatible hydrogels, primary capsular fibroblasts, monocyte-derived macrophages and HUVEC cells, we generated stable PDO cultures which exhibited key disease phenotypes, including vascularization, increased stiffness, and an expanded lining layer over 21 days of culture. Through further investigation of cell-matrix and cell-cell interactions in the organoid model, we intend to unpack the differences between resolving and non-resolving fibrotic disease and uncover clinically relevant therapeutic targets for fibrosis


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 59 - 59
2 Jan 2024
Depboylu F
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Production of porous titanium bone implants is a highly promising research and application area due to providing high osseointegration and achieving the desired mechanical properties. Production of controlled porosity in titanium implants is possible with laser powder bed fusion (L- PBF) technology. The main topics of this presentation includes the L-PBF process parameter optimization to manufacture thin walls of porous titanium structures with almost full density and good mechanical properties as well as good dimensional accuracy. Moreover, the cleaning and coating process of these structures to further increase osseointegration and then in-vitro biocompatibility will be covered


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_16 | Pages 42 - 42
17 Nov 2023
Prabhakaran V Sobrattee A Melchels FP Paxton JZ
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Abstract. Objectives. The enthesis is a specialised structure at the interface between bone and tendon with gradual integration to maintain functionality and integrity. In the process of fabricating an in-vitro model of this complex structure, this study aims to investigate growth and maturation of bone, tendon and BMSC spheroids followed by 3D mini-tissue production. Methods. Cell spheroids Spheroids of differentiated rat osteoblasts (dRObs), rat tendon fibroblasts (RTFs) and bone marrow stem cells (BMSC) were generated by culturing in 96 well U bottom cell repellent plates. With dROb spheroids previously analysed [1], RTF spheroids were examined over a duration of up to 28 days at different seeding densities 1×10. 4. , 5×10. 4. , 1×10. 5. , 2×10. 5. in different media conditions with and without FBS (N=3). Spheroid diameter was analysed by imageJ/Fiji; Cell proliferation and viability was assessed by trypan blue staining after dissociating with accutase + type II collagenase mix; necrotic core by H&E staining; and extracellular matrix by picro-sirius red (RTFs) staining to visualise collagen fibres under bright-field and polarised light microscope. 3D mini-tissue constructs. 15 day old mineralised dROb spheroids (∼1.5mm diameter) were deposited in pillar array supports using a customised spheroid deposition system to allow 3D mini-tissue formation via fusion (N=3). Similarly BMSC and RTF spheroids were deposited after determining the seeding density that produced spheroid size equivalent to 15 day old dROb spheroids. Gentle removal of spheroids from supports was performed on day 2, 4 and 6 to assess spheroid fusion. Histological staining was performed to observe cellular arrangement and extracellular matrix. Results. RTF spheroids diameter reduced over the course of 28 days regardless of the seeding density. A substantial decline in cell numbers over time was observed and suggests lack of cell proliferation due to tenogenic differentiation. Absence of a necrotic core in RTF spheroids, in all seeding densities, reveals their inherent capacity to maintain cell viability in avascular conditions. Picro-sirius red staining demonstrated the presence of collagen type I fibres predominantly in peripheral regions of spheroids maintaining its shape. Small amounts of collagen type III were also noticed. The dROb spheroids fused rapidly within 2 days resulting in the formation of a mini-tissue. 2×10. 5. RTFs and 3×10. 5. BMSCs produced spheroids of ∼1.5mm on day 3 and day 1 respectively. When these spheroids were deposited in pillar array supports, they did not undergo fusion even up to 6 days. This suggests inadequate aggregation of spheroids and insufficient ECM production at this early stage. Conclusions. This study has demonstrated the ability of RTFs to produce necrotic core-free spheroids with collagen fibres maintaining their structural integrity. For mini-tissue formation, we predict a longer initial culture time of RTF and BMSC spheroids will allow increased cellular interaction and ECM production before deposition, and will facilitate spheroid fusion. These findings will be applied in producing heterogenous mini-tissues, serving as a 3D in-vitro enthesis model. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 88 - 88
4 Apr 2023
Anjum S Kirby J Deehan D Tyson-Capper A
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The most common reason for revision surgery of total hip replacements is aseptic loosening of implants secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can cause pseudotumour formation. As revision surgery is associated with higher mortality and infection, it is important to understand the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4) has been shown to mediate immune responses to cobalt ions. Statin use in epidemiological studies has been associated with reduced risk of revision surgery. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses and there is evidence that statins can modulate TLR4 activity. This study investigates simvastatin's effect on orthopaedic biomaterial-mediated changes in protein expression of key inflammatory markers and soluble-ICAM-1 (sICAM-1), an angiogenic factor implicated in pseudotumour formation. Human macrophage THP-1 cells were pre-incubated with 50µM simvastatin for 2-hours or a vehicle control (VC), before being exposed to 0.75mM cobalt chloride, 50μm3 per cell zirconium oxide or LPS as a positive control, in addition to a further 24-hour co-incubation with 50µM simvastatin or VC. Interleukin −8 (IL-8), sICAM-1, chemokine ligand 2 (CCL2), CCL3 and CCL4 protein secretion was measured by enzyme-linked immunosorbent assay (ELISA). GraphPad Prism 10 was used for statistical analysis including a one-way ANOVA. Pre-treatment with simvastatin significantly reduced LPS and cobalt-mediated IL-8 secretion (n=3) and sICAM-1 protein secretion (n=2) in THP-1 cells. Pre-treatment with simvastatin significantly reduced LPS-mediated but not cobalt ion-mediated CCL2 (n=3) and CCL3 protein (n=3) secretion in THP-1 cells. Simvastatin significantly reduced zirconium oxide-mediated CCL4 secretion (n=3). Simvastatin significantly reduced cobalt-ion mediated IL-8 and sICAM-1 protein secretion in THP-1 cells. This in-vitro finding demonstrates the potential for simvastatin to reduce recruitment of leukocytes which mediate the deleterious inflammatory processes driving implant failure


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 22 - 22
23 Feb 2023
Sandow M Cheng Z
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Arthroscopic electrosurgical tools for ablative, desiccating or coagulative effect are delivered as monopolar or bipolar probes. Monopolar electrosurgery delivers various profiles of heat energy directly to the tissue within a non-conductive irrigant (such as water or glycine) whereas bipolar electrosurgery creates an energy source by producing an electrical arc between the bipolar electrodes on the instrument head within an electro-conductive irrigation solution (saline) - and the heat generated is then transferred to the target tissues. This study investigated the heat generation within the simulated in-vitro test model to review the level of local heat production and potential local tissue heat. In a simulated In-vitro testing environment the local heat generation using bipolar or monopolar electrosurgical probes at standard power setting in either saline or water was tested, both touching and not touching a simulated tissue target, and for variable on-times. Monopolar generated relatively little heat when used in water and not touching the tissue. By contrast the bipolar wand generated potentially damaging local tissue temperature rises when used in saline and not touching the tissue. Both probes generated high local tissue heat when touching the tissue in their recommended irrigation solution. Monopolar electrosurgery delivered high localized temperature to the simulated tissue surface, but produced relatively little heat when not touching the tissue in a water solution. Bipolar however created high local temperature within the fluid adjacent to the probe irrespective if it was touching the tissue or not. Activation of the bipolar probe away from the tissue in saline irrigation may create a potential harmful temperature within the fluid medium without delivering therapeutic thermal effect to the target tissues. Monopolar electrosurgery appears to deliver a more controlled thermal effect, and only when in contact with the target tissues – potentially creating a reduced collateral thermal footprint


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 52 - 52
10 Feb 2023
Di Bella C
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3D printing and Bioprinting technologies are becoming increasingly popular in surgery to provide a solution for the regeneration of healthy tissues. The aim of our project is the regeneration of articular cartilage via bioprinting means, to manage isolated chondral defects. Chrondrogenic hydrogel (chondrogel: GelMa + TGF-b3 and BMP6) was prepared and sterilised in our lab following our standard protocols. Human adipose-derived mesenchymal stem cells were harvested from the infrapatellar fat pad of patients undergoing total knee joint replacements and incorporated in the hydrogel according to our published protocols. The chondrogenic properties of the chondrogel have been tested (histology, immunohistochemistry, PCR, immunofluorescence, gene analysis and 2. nd. harmonic generation microscopy) in vitro and in an ex-vivo model of human articular defect and compared with standard culture systems where the growth factors are added to the media at repeated intervals. The in-vitro analysis showed that the formation of hyaline cartilage pellet was comparable between the two strategies, with a similar metabolic activity of the cells. These results have been confirmed in the ex-vivo model: hyaline-like cartilage was observed within the chondral defect in both the chondrogel group and the control group after 28 days in culture. The use of bioprinting techniques in vivo requires the ability of stem cells to access growth factors directly in the environment they are in, as opposed to in vitro techniques where these factors are provided externally at recurrent intervals. This study showed the successful strategy of incorporating chondrogenic growth factors for the formation of hyaline-like cartilage in vitro and in an ex-vivo model of chondral loss. The incorporation of chondrogenic growth factors in a hydrogel is a possible strategy for articular cartilage regeneration


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 78 - 78
1 Dec 2022
Dilernia FD Watson D Heinrichs D Vasarhelyi E
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Staphylococcus aureus is the most frequently isolated organism in periprosthetic joint infections. The mechanism by which synovial fluid (SF) kills bacteria has not yet been elucidated, and a better understanding of its antibacterial characteristics is needed. We sought to analyze the antimicrobial properties of exogenous copper in human SF against S. aureus. SF samples were collected from patients undergoing total elective knee or hip arthroplasty. Different S. aureus strains previously found to be sensitive and resistant, UAMS-1 and USA300 WT, respectively, were used. We performed in-vitro growth and viability assays to determine the capability of S. aureus to survive in SF with the addition of 10µM of copper. We determined the minimum bactericidal concentration of copper (MBC-Cu) and evaluated the sensitivity to killing, comparing WT and CopAZB-deficient USA300 strains. UAMS-1 evidenced a greater sensitivity to SF when compared to USA300 WT, at 12 (p=0.001) and 24 hours (p=0.027). UAMS-1 significantly died at 24 hours (p=0.017), and USA300 WT survived at 24 hours. UAMS-1 was more susceptible to the addition of copper at 4 (p=0.001), 12 (p=0.005) and 24-hours (p=0.006). We confirmed a high sensitivity to killing with the addition of exogenous copper on both strains at 4 (p=0.011), 12 (p=0.011), and 24 hours (p=0.011). Both WT and CopAZB-deficient USA300 strains significantly died in SF, evidencing a MBC-Cu of 50µM against USA300 WT (p=0.011). SF has antimicrobial properties against S. aureus, and UAMS-1 was more sensitive than USA300 WT. The addition of 10µM of copper was highly toxic for both strains, confirming its bactericidal effect. We evidenced CopAZB-proteins involvement in copper effluxion by demonstrating the high sensitivity of the mutant strain to lower copper concentrations. Thus, we propose CopAZB-proteins as potential targets and the use of exogenous copper as possible treatment alternatives against S. aureus


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 43 - 43
1 Oct 2022
Moore K Li A Gupta N Price B Delury C Laycock P Aiken S Stoodley P
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Aim. Multispecies biofilms are associated with difficult periprosthetic joint infections (PJI), particularly if they have different antibiotic sensitivities. We aimed to determine if we could generate and kill a multispecies biofilm consisting of a Gram negative and Gram positive pathogen in-vitro with antibiotic loaded calcium sulfate beads containing single or combination antibiotics. Methods. To establish whether we could co-culture mixed species biofilms various combinations of Pseudomonas aeruginosa (PA), Enterococcus faecalis (EF), Staphylococcus aureus (SA) and Enterobacter faecalis (EF) were grown together on 316L stainless steel coupons and agar plates. Based on this screen we focused on PA + EF and challenged them with high purity calcium sulfate beads (Stimulan Rapid Cure) loaded with vancomycin (V), alone tobramycin (T) alone or vancomycin and tobramycin in combination (V+T). Bioluminescence, light imaging, plate count, confocal microscopy and scanning electron microscopy were used to quantify growth. Results. On 316LSS the V loaded bead reduced both EF and PA by approximately 2 logs compared to unloaded control beads. A T alone loaded bead eliminated PA from the dual species biofilm and caused a 2-log reduction in EF. The V+T-beads reduced PA by 9-logs and EF by 8.3 logs. In terms of total CFUs V+T beads reduced the bioburden by 8.4 logs compared to V or T alone. which resulted in 2.1 and 2.6 log reductions respectively. (* P<0.05, *** P<0.001). On agar PA dominated the culture for the unloaded and V loaded beads. However, when challenged with a T loaded bead both species were able to coexist and a zone of killing was generated in both species in the multispecies biofilms. However, this zone was smaller and included more tolerant variants than the zone generated by V+T-loaded beads. Conclusions. There were species proportion differences between biofilms grown on agar and 316LSS demonstrating the importance of growth conditions on species interactions. Antibiotics against strains with differing sensitivities can shift species interactions. High purity calcium sulfate beads containing tobramycin a broad-spectrum Gram positive and negative antibiotic vancomycin, a Gram-positive targeted antibiotic killed a larger percentage of a multispecies in an in-vitro biofilm than either single gram-specific antibiotic alone, demonstrating the advantage of using combination antibiotics for treating multispecies biofilms


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 18 - 18
1 Dec 2021
Brown M Wilcox R Isaac G Anderson J Board T Williams S
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Abstract. OBJECTIVES. Dual mobility (DM) total hip replacements (THRs) were introduced to reduce the risk of hip dislocation in at-risk patients. DM THRs have shown good overall survivorship and low rates of dislocation, however, the mechanisms which describe how these bearings function in-vivo are not fully understood. This is partly due to a lack of suitable characterisation methodologies which are appropriate for the novel geometry and function of DM polyethylene liners, whereby both surfaces are subject to articulation. This study aimed to develop a novel semi-quantitative geometric characterisation methodology to assess the wear/deformation of DM liners. METHODS. Three-dimensional coordinate data of the internal and external surfaces of 14 in-vitro tested DM liners was collected using a Legex 322 coordinate measuring machine. Data was input into a custom Matlab script, whereby the unworn reference geometry was determined using a sphere fitting algorithm. The analysis method determined the geometric variance of each point from the reference surface and produced surface deviation heatmaps to visualise areas of wear/deformation. Repeatability of the method was also assessed. RESULTS. Semi-quantitative analysis of the surface deviation heatmaps revealed circumferential damage patterns similar to those reported in the literature. Additionally, the location of the damaged regions corresponded between the internal and external surfaces. Comparing five repeat measurements of the same liner, the maximum geometric variance of each surface varied by 1 µm (standard deviation) suggesting a high repeatability of the method. CONCLUSIONS. This study presents an effective and highly repeatable characterisation methodology to semi-quantitatively assess the wear/deformation of in-vitro tested DM liners. This method is suitable for the analysis of retrieved DM liners whereby no pre-service information is available, which may provide information about the complex in-vivo kinematics and mechanical failure mechanisms of these bearings


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 12 - 12
1 Nov 2021
Anjum S Jamieson S Deehan D Kirby J Tyson-Capper A
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Introduction and Objective. Total joint replacement is indicated for osteoarthritis where conservative treatment has failed, and in the UK the number of patients requiring hip and knee replacements is set to increase with an ageing population. Survival of total hip replacements is around 85% at 20 years with the most common reason for revision being aseptic loosening of the implant secondary to osteolysis, which is caused by immune-mediated reactions to implant debris. These debris can also cause pseudotumour formation. As revision surgery is associated with higher morbidity, mortality, infection rates, venous thromboembolism, resource demand and poorer subsequent function it is important to understand the mechanisms underlying the pro-inflammatory process to improve implant survival. Toll-like receptor 4 (TLR4), an innate immune receptor, has been demonstrated to mediate deleterious immune responses by the Tyson-Capper research group, including inflammatory cytokine interleukin-8 (IL-8) secretion. Statin use in epidemiological studies has been associated with reduced overall risk of revision surgery after hip replacement. In-vitro studies have demonstrated the potential for statins to reduce orthopaedic debris-induced immune responses which can lead to osteolysis and pseudotumour formation. As literature from cardiological investigations demonstrate that statins can reduce the expression and responsiveness of TLR4, this could be an exciting mechanism to exploit to reduce the host immune response to orthopaedic wear debris, thereby improving implant survival by reducing immune mediated osteolysis. This ongoing study investigates simvastatin's effect on cobalt ion-mediated changes in gene and protein expression of interleukin-8 and soluble-ICAM-1 (sICAM-1) which is an angiogenic factor implicated in pseudotumour formation. Materials and Methods. TLR4-expressing human monocyte/macrophage THP-1 cells were pre-incubated with 50μM simvastatin for 2-hours or a vehicle control, before being exposed to exposed to 0.75mM cobalt chloride, in addition to a further 24-hour co-incubation with 50μM simvastatin or vehicle control. IL-8 protein and sICAM-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression changes were quantified by TaqMan-based real time polymerase chain reaction. Results. Pre-treatment with simvastatin significantly reduced cobalt-mediated IL-8 protein secretion (n=3) and sICAM-1 protein secretion (n=2) in THP-1 cells (p-value<0.0001). Work will be undertaken to determine changes in gene expression, the role of TLR4 in these responses and the effect of simvastatin on additional inflammatory markers. Conclusions. Simvastatin significantly reduces cobalt-ion mediated IL-8 and sICAM-1 protein secretion in THP-1 cells. This in-vitro finding demonstrates the potential for simvastatin to reduce recruitment of leukocytes which mediate the deleterious inflammatory processes driving aseptic loosening and pseudotumour formation


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 15 - 15
1 Mar 2021
Kadar A Haddara M Fan S Chinchalkar S Ferreira L Suh N
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Normal digital flexion relies on flexor tendon pulleys to transmit linear muscular force to angular digital motion. Despite the critical role these pulleys play, there is a growing trend among surgeons to partially sacrifice or “vent” them during flexor tendon repair to improve surgical exposure. Although this new practice is reported to improve outcomes after flexor tendon repair, there is concern for the long-term effects of bowstringing, reduced finger range of motion (ROM) and altered tendon biomechanics. The objective of this study was to examine the effects of the application of a thermoplastic ring, acting as an “external” pulley, on flexor tendon biomechanics and finger ROM. We hypothesized that the application of an external thermoplastic ring would produce a centripetal force over the tendon to reduce bowstringing, improve finger ROM, and restore tendon loads following pulley venting. Twelve digits comprised of the index, long, and ring fingers from four cadaveric specimens were tested using a novel in-vitro active finger motion simulator. Servo-motors were used to generate motion. Loads induced by flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP), and joint range of motion were measured with each sequential sectioning of the A2, A3, and A4 flexor pulley, in comparison to a native healthy finger condition. At each finger condition, A2 and A4 external thermoplastic pulley rings were applied over the proximal phalanx and middle phalanx, respectively, to recreate A2 and A4 function. Results were recorded and analyzed using a one way repeated-measures ANOVA. Following venting of the A2, A3 and A4 pulley, proximal interphalangeal joint (PIPJ) ROM significantly decreased by 17.02 ± 8.42 degrees and distal interphalangeal joint (DIPJ) range of motion decreased by 17.25 ± 8.68 degrees compared to intact pulleys. Application of the external rings restored range of motion to within 8.14 ± 8.17 degrees at the PIPJ and to within 7.72 ± 8.95 degrees at the DIPJ. Similarly, pulley venting resulted in a 36% reduction in FDS load and 50% in FDP load compared to intact pulleys. Following application of the external rings, loads were almost restored to normal at 7% reduction for FDS load and 13% reduction for FDP load. Venting of flexor tendon pulleys significantly alters flexor tendon biomechanics and digit range of motion. The application of thermoplastic rings acting as external pulleys over the proximal and middle phalanges is an effective, inexpensive, non-invasive and reproducible therapeutic method to restore flexor tendon biomechanics and digit range of motion


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 13 - 13
1 Mar 2021
Chambers S Padmore C Fan S Grewal R Johnson J Suh N
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To determine the biomechanical effect of increasing scaphoid malunion and scaphoid non-union on carpal kinematics during dynamic wrist motion using an active wrist motion simulator. Seven cadaveric upper extremities underwent active wrist flexion and extension in a custom motion wrist simulator with scaphoid kinematics being captured with respect to the distal radius. A three-stage protocol of progressive simulated malunion severity was performed (intact, 10° malunion, 20° malunion) with data analyzed from 45° wrist flexion to 45° wrist extension. Scaphoid malunions were modelled by creating successive volar wedge osteotomies and fixating the resultant scaphoid fragments with 0.062 Kirshner wires. At the completion of malunion motion trials, a scaphoid non-union trial was carried out by removing surgical fixation to observe motion differences from the malunion trials. Motion of the scaphoid, lunate, capitate, and trapezium-trapezoid was recorded and analyzed using active optical trackers. Increasing scaphoid malunion severity did not significantly affect scaphoid or trapezium-trapezoid motion (p>0.05); however, it did significantly alter lunate motion (p<0.001). Increasing malunion severity resulted in progressive lunate extension across wrist motion (Intact – Mal 10: mean dif. = 7.1° ± 1.6, p<0.05; Intact – Mal 20: mean dif. = 10.2° ± 2.0, p<0.05;) although this change was not as great as the difference seen during non-union trials (native – non-union: mean dif. = 13.8° ± 3.7, p<0.05). In this in-vitro model, increasing scaphoid malunion severity was associated with progressive extension of the lunate in all wrist positions. The clinical significance of this motion change is yet to be elucidated, but this model serves as a basis for understanding the kinematic consequences of scaphoid malunion deformities


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 47 - 47
1 Mar 2021
Hayward SJ Lammey GP Gheduzzi S Miles AW Keogh PS
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Abstract. Introduction. Altered mechanical loading is a contributing factor to low back pain, a condition affecting 80% of the population at some point in life. A plethora of in-vitro studies exist focusing on 6 degree of freedom (dof) testing of functional spinal units (FSU) to obtain a specimen stiffness matrix. Due to differences in the performance of test apparatus and in the technique used to manipulate raw data it is difficult to compare results from different groups. Objectives. Our primary objective was to develop a standardised technique to benchmark the performance of testing apparatus; a secondary objective was to standardise the data manipulation technique. Methods. 6 tests each at 250N and 500N preload were performed on synthetic FSU specimens using the Bath spine simulator, with a further 3 tests performed on porcine specimens. Three techniques were used to evaluate stiffness: first the slope of the entire load-displacement curve, inclusive of loading and unloading portions, was considered, secondly zonal stiffnesses were defined by dividing the load displacement curve into elastic and neutral zones, finally stiffness was calculated only for the loading portion of the elastic and neutral zone. The standard error of the residuals was used to compare results. Results. The stiffness matrix principal elements of the synthetic FSU showed repeatability of 3.2% and reflected specimen symmetry in the x and y (8% error). The stiffness calculation techniques including both loading and unloading portions of the curve were affected by hysteresis, an issue that did not arise when only the loading portion was used in calculations. Conclusions. It is recommended that testing apparatus performance is evaluated with synthetic specimens, to allow benchmarking against different set-ups. Furthermore, it is recommended that stiffness calculations are performed only on the loading part of the curve to eliminate the influence of hysteresis on the results. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_5 | Pages 15 - 15
1 Jul 2020
Holleyman R Critchley R Jameson S Mason J Reed M Malviya A
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Prosthetic joint infections (PJI) are a devastating consequence in total hip arthroplasties (THA) with both significant morbidity and sometimes mortality, posing a significant health economic burden. Studies, both clinical and in-vitro have suggested possible reduction in PJI with the use of ceramic bearings. We have investigated the relationship of ceramic-on-ceramic (CoC), ceramic-on-polyethylene (CoP) or metal-on-polyethylene (MoP) bearing surface in affecting outcome of revision surgery after primary THA using data collected from National Joint Registry for England and Wales, Northern Ireland and the Isle of Man between 2002 and 2016. We used a competing risk regression model to investigate predictors of each revision outcome, such as infection, dislocation, aseptic revision and all cause revisions. The results were adjusted for age, gender, ASA grade, BMI, indication for surgery, intraoperative complications and implant data. We identified 456,457 THA (228,786 MoP, 128,403 CoC and 99,268 CoP). In a multivariable model, the adjusted risk of revision for PJI was lower with CoC (OR-0.748, p<0.001) and CoP (OR-0.775, p<0.001) when compared to MoP bearing. Additionally there was also a significant reduction in the risk of all cause revision for CoC (OR-0.918, p=0.002) and CoP (0.806, p<0.001), bearings as compared with MoP. The protective effect of ceramic bearing was predominantly seen after two years of implantation with a significant (p<0.0001) reduction of revision for PJI in both CoC (by 42.8%) and CoP (by 41.3%) group. Similarly significant effect was seen for aseptic revision beyond two years and overall all cause revision rate beyond two years reduced by 21.6% for CoC and 27.1% for CoP (p<0.001). Within the limits of registry analysis, this study has demonstrated an association between the use of ceramic bearing and lower rates of revision for all cause revisions especially infection and aseptic loosening. This finding supports the use of ceramic bearings in THA


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 45 - 45
1 Jul 2020
Langohr G DeDecker S Khayat A Johnson J King GJ Medley J
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Joint hemiarthroplasty replaces one side of a synovial joint and is a viable alternative to total joint arthroplasty when one side of the joint remains healthy. Most hemiarthroplasty implants used in current clinical practice are made from stiff materials such as cobalt chrome or ceramic. The substitution of one side of a soft cartilage-on-cartilage articulation with a rigid implant often leads to damage of the opposing articular cartilage due to the resulting reductions in contact area and increases in cartilage stress. The improvement of post-operative hemiarthroplasty articular contact mechanics is of importance in advancing the performance and longevity of hemiarthroplasty. The purpose of the present study was to investigate the effect of hemiarthroplasty surface compliance on early in-vitro cartilage wear and joint contact mechanics. Cartilage wear tests were conducted using a six-station pin-on-plate apparatus. Pins were manufactured to have a hemispherical radius of curvature of 4.7 mm using either Bionate (DSM Biomedical) having varying compliances (80A [E=20MPa], 55D [E=35MPa], 75D [E=222MPa], n=6 for each), or ceramic (E=310GPa, n=5). Cartilage plugs were cored from fresh unfrozen bovine knee joints using a 20 mm hole saw and mounted in lubricant-containing chambers, with alpha calf serum diluted with phosphate buffer solution to a protein concentration of 17 g/L. The pins were loaded to 30N and given a stroke length of 10 mm for a total of 50,000 cycles at 1.2 Hz. Volumetric cartilage wear was assessed by comparing three-dimensional cartilage scans before and during wear testing. A two-way ANOVA was used for statistical analysis. To assess hemiarthroplasty joint contact mechanics, 3D finite element modelling (ABAQUS v6.12) was used to replicate the wear testing conditions. Cartilage was modeled using neo-Hookean hyper-elastic material properties. Contact area and peak contact stress were estimated. The more compliant Bionate 80A and 55D pins produced significantly less volumetric cartilage wear compared with the less compliant Bionate 75D and ceramic pins (p 0.05). In terms of joint contact mechanics, the more compliant materials (Bionate 80A and 55D) had significantly lower maximum contact stress levels compared to the less compliant Bionate 75D and ceramic pins (p < 0 .05). The results of this study show a relationship between hemiarthroplasty implant surface compliance and early in vitro cartilage wear, where the more compliant surfaces produced significantly lower amounts of cartilage wear. The results of the joint contact mechanics analysis showed that the more compliant hemiarthroplasty materials produced lower maximum cartilage contact stresses than the less compliant materials, likely related to the differences in wear observed. More compliant hemiarthroplasty surfaces may have the potential to improve post-operative cartilage contact mechanics by increasing the implant-cartilage contact area while reducing peak contact stress at the implant-cartilage interface, however, such materials must be resistant to surface fatigue and longer-term cartilage wear/damage must be assessed


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_1 | Pages 106 - 106
1 Feb 2020
Wise C Oladokun A Maag C
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Introduction. Femoral neck impingement occurs clinically in total hip replacements (THR) when the acetabular liner articulates against the neck of a femoral stem prosthesis. This may occur in vivo due to factors such as prostheses design, patient anatomical variation, and/or surgical malpositioning, and may be linked to joint instability, unexplained pain, and dislocation. The Standard Test Method for Impingement of Acetabular Prostheses, ASTM F2582 −14, may be used to evaluate acetabular component fatigue and deformation under repeated impingement conditions. It is worth noting that while femoral neck impingement is a clinical observation, relative motions and loading conditions used in ASTM F2582-14 do not replicate in vivo mechanisms. As written, ASTM F2582-14 covers failure mechanism assessment for acetabular liners of multiple designs, materials, and sizes. This study investigates differences observed in the implied and executed kinematics described in ASTM F2582-14 using a Prosim electromechanical hip simulator (Simulation Solutions, Stockport, Greater Manchester) and an AMTI hydraulic 12-station hip simulator (AMTI, Watertown, MA). Method. Neck impingement testing per ASTM F2582-14 was carried out on four groups of artificially aged acetabular liners (per ASTM F2003-15) made from GUR 1020 UHMWPE which was re-melted and cross-linked at 7.5 Mrad. Group A (n=3) and B (n=3) consisted of 28mm diameter femoral heads articulating on 28mm ID × 44mm OD acetabular liners. Group C (n=3) and D (n=3) consisted of 40mm diameter femoral heads articulating on lipped 40mm ID × 56mm OD 10° face changing acetabular liners. All acetabular liners were tested in production equivalent shell-fixtures mounted at 0° initial inclination angle. Femoral stems were potted in resin to fit respective simulator test fixtures. Testing was conducted in bovine serum diluted to 18mg/mL protein content supplemented with sodium azide and EDTA. Groups A and C were tested on a Prosim; Groups B and D were tested on an AMTI. Physical examination and coordination measurement machine (CMM) analyses were conducted on all liners pre-test and at 0.2 million cycle intervals to monitor possible failure mechanisms. Testing was conducted for 1.0 million cycles or until failure. An Abaqus/Explicit model was created to investigate relative motions and contact areas resulting from initial impingement kinematics for each test group. Results. Effects of kinematic differences in the execution of ASTM F2582-14 were observed in the four groups based on simulator type (Figure 1) and liner design. The Abaqus/Explicit FEA model revealed notable differences in relative motions and contact points (Figure 2) between specimen components i.e. acetabular liner, femoral head, and femoral stem throughout range of motion. Acetabular liner angular change within shell-fixtures, rim deformation, crack propagation, and metal-on-metal contact between acetabular shell-fixtures and femoral stems were observed as potential failure mechanisms (Figure 3) throughout testing. These mechanisms varied in severity by group due to differing contact stresses and simulator constraints. Significance. Investigating failure mechanisms caused by altered kinematics of in-vitro neck impingement testing, due to influences of simulator type and acetabular liner design, may aid understanding of failure mechanisms involved when assessing complaints/retrievals and influence future prosthetic designs. For any figures or tables, please contact the authors directly