Multiple myeloma (MM) is an incurable hematological tumor stemming from malignant plasma cells. MM cells accumulate in the bone marrow (BM) and shape the BM niche by establishing complex interactions with normal BM cells, boosting osteoclasts (OCLs) differentiation and causing bone disease. This unbalance in bone resorption promotes tumor survival and the development of drug resistance. The communication between tumor cells and stromal cells may be mediated by: 1) direct cell-cell contact; 2) secretion of soluble factors, i.e. chemokines and growth factors; 3) release of extracellular vesicles/exosomes (EVs) which are able to deliver mRNAs, miRNAs, proteins and metabolites in different body district. Primary CD138+ MM cells were isolated from patients BM aspirates. MM cell lines were cultured alone in complete RPMI-1640 medium or co-cultured with murine (NIH3T3) or human (HS5) BMSC cell lines or murine Raw264.7 monocytes in DMEM medium supplemented with 10% V/V FBS. Silencing of Jagged1 and Jagged2 was obtained by transient expression of specific siRNAs or by lentiviral transduction using a Dox-inducible system (pTRIPZ). EVs were isolated using differential ultracentrifugation. EVs concentration and size were analyzed using Nano Track Analysis (NTA) system. The uptake of PKH26-labelled MM-derived EVs by HS5 or Raw264.7 was measured after 48 hours by confocal microscopy and flow cytometry. Osteoclast (OCL) differentiation of Raw264.7 cells was induced by 50ng/ml mRANKL, co-culturing with MM cells, CM or EVs. OCLs were stained by TRAP Kit and counted. Bone resorption was assessed by Osteo Assay Surface plates. Flow cytometric detection of apoptotic cells was performed after staining with Annexin V. Gene expression was analyzed by qRT-PCR, while protein levels were determined using flow cytometry ELISA or WB. Notch oncogenic signaling is dysregulated in several hematological and solid malignancies. Notch receptors and ligands are key players in the crosstalk between tumor cells and BM cells. We have demonstrated that: 1) the dysregulated Jagged ligands on MM cells trigger the activation of Notch receptors in the nearby stromal cells by cell-cell contact. This results in the release of anti-apoptotic and growth stimulating factors, i.e. IL6 and SDF1; 2) MM cells promote the development of bone lesions boosting osteoclast differentiation by secreting soluble factors (i.e. RANKL) and by the activation of Notch signaling mediated by direct contact with osteoclast precursors; 3) Finally, we present evidences that EVs play a crucial role in the dysregulated interactions of MM cells with the microenvironment and that Notch signaling regulates their release and participate in this cross-talk. These evidences supports the hypothesis that Jagged targeting on MM cells may interrupt the communication between tumor cells and the surrounding milieu, blocking the activation of the oncogenic Notch pathway and finally resulting in the a reduction of MM-associated bone disease and drug resistance

We undertook a study on eight arms from fresh cadavers to define the clinical usefulness of the lesser sigmoid notch as a landmark when reconstructing the length of the neck of the radius in replacement of the head with a prosthesis. The head was resected and its height measured, along with several control measurements. This was compared with in situ measurements from the stump of the neck to the proximal edge of the lesser sigmoid notch of the ulna. All the measurements were performed three times by three observers acting independently. The results were highly reproducible with intra- and interclass correlations of > 0.99. The mean difference between the measurement on the excised head and the distance from the stump of the neck and the lesser sigmoid notch was −0.02 mm (−1.24 to +0.97). This difference was not statistically significant (p = 0.78). The proximal edge of the lesser sigmoid notch provides a reliable landmark for positioning a replacement of the radial head and may have clinical application

Growth factors produced by inflammatory cells and mesenchymal progenitors are required for proper bone regeneration. Signaling pathways activated downstream of these proteins work in concert and synergistically to drive osteoblast and/or chondrocyte differentiation. While dysregulation can result in abnormal healing, activating these pathways in the correct spatiotemporal context can enhance healing. Bone morphogenetic protein (BMP) signaling is well-recognized as being required for bone regeneration, and BMP is used clinically to enhance bone healing. However, it is imperative to develop new therapeutics that can be used alone or in conjunction with BMP to drive even more robust healing. Notch signaling is another highly conserved signaling pathway involved in tissue development and regeneration. Our work has explored Notch signaling during osteoblastogenesis and bone healing using both in vitro studies with human primary mesenchymal progenitor cells and in vivo studies with genetically modified mouse models. Notch signaling is required and sufficient for osteoblast differentiation, and is required for proper bone regeneration. Indeed, intact Notch signaling through the Jagged-1 ligand is required for BMP induced bone formation. On-going work continues to explore the intersection between BMP and Notch signaling, and determining cell types that express Notch receptors and Notch ligands during bone healing. Our long-term objective is to develop Notch signaling as a clinical therapy to repair bone

The incisura fibularis (IF) provides intrinsic stability to the ankle joint complex by interlocking the distal tibia and fibula. Despite a high frequency of ligamentous ankle injuries, scant attention has been given to the morphology of the IF morphology incisura fibularis in the onset and development of these lesions. Therefore, we systematically reviewed the relation between ligamentous ankle disorders and the morphometrics of the IF. A systematic literature search was conducted on following databases: PubMed, Embase and Web of Science. Search terms consisted of ‘ankle trauma’, ‘ankle injury’, ‘ankle sprain’, ‘ankle fracture’, ‘tibiofibular’, ‘fibular notch’, ‘fibular incisura’, ‘incisura fibularis’, ‘morphometric analysis’, ‘ankle syndesmosis’, ‘syndesmotic stability’. The evaluation instrument developed by Hawker et al. was used to assess the quality of the selected studies. This protocol was performed according to the PRISMA guidelines and is registered on PROSPERO (CRD42021282862). Nineteen studies were included and consisted of prospective cohort (n=1), retrospective comparative (n=10), and observational (n=8) study design. Comparative studies have found certain morphological characteristics in patients with ankle instability. Several studies (n=5) have correlated a shallow IF depth with a higher incidence of ankle injury. A significant difference has also been found concerning the incisura height and angle (n=3): a shorter incisura and more obtuse angle have been noted in patients with ankle sprains. The mean Hawker score was 28 out of 36 (range=24-31). A shallower IF is associated with ligamentous ankle lesions and might be due to a lower osseous resistance against tibiofibular displacement. However, these results should be interpreted in light of moderate methodological quality and should always be correlated with clinical findings. Further prospective studies are needed to further assess the relation between the incisura morphometrics and ligamentous disorders of the ankle joint. Keywords: ankle instability, ankle injury, incisura fibularis, fibular notch, tibiofibular morphometrics, ankle syndesmosis

This study aims to assess the fracture mechanics of type-2 diabetic (T2D) femoral bone using innovative site-specific tests, whilst also examining the cortical and trabecular bone microarchitecture from various regions using micro-computed tomography (CT) of the femur as the disease progresses. Male [Zucker Diabetic Fatty (ZDF: fa/fa) (T2D) and Zucker Lean (ZL: fa/+) (Control)] rats were euthanized at 12-weeks of age, thereafter, right and left femora were dissected (Right femora: n = 6, per age, per condition; Left femora: n=8-9, per age, per condition). Right femurs were notched in the posterior of the midshaft. Micro-CT was used to scan the proximal femur, notched and unnotched femoral midshaft (cortical) of the right femur and the distal metaphysis (trabecular) of the left femur to investigate microarchitecture and composition. Right femurs were fracture toughness tested to measure the stress intensity factor (Kic) followed by a sideways fall test using a custom-made rig to investigate femoral neck mechanical properties. There was no difference in trabecular and cortical tissue material density (TMD) between T2D and control rats. Cortical thickness was unchanged, but trabeculae were thinner (p<0.01) in T2D rats versus controls. However, T2D rats had a greater number of trabeculae (p<0.05) although trabecular spacing was not different to controls. T2D rats had a higher connectivity distribution (p<0.05) and degree of anisotropy (p<0.05) in comparison to controls. There was no difference in the mechanical properties between strains. At 12-weeks of age, rats are experiencing early-stage T2Ds and the disease impact is currently not very clear. Structural and material properties are unchanged between strains, but the trabecular morphology shows that T2D rats have more trabecular struts present in order to account for the thinner trabeculae

Introduction. Distal femur fractures around a total knee arthroplasty (TKA) are a growing problem for orthopaedic surgeons. The purpose of this study was to identify risks of reoperation for nonunion following open reduction and internal fixation of TKA periprosthetic distal femur fractures (PDFF). Method. Patients with PDFF (AO 33A-C[VB1, C1, D1], Su types 1-3) managed operatively with open reduction and internal fixation (ORIF) were retrospectively reviewed. Exclusion criteria were acute management with a distal femur replacement, less than 6 months of follow-up, and lack of injury or follow-up radiographs. The primary outcome measure was reoperation to achieve bony union. Comparisons were made between cases that did and did not require a reoperation to achieve union. Univariate analysis was used to identify factors to be analyzed in multivariate analysis to determine independent risk factors for the primary outcome. Result. A total of 77 patients met inclusion criteria. Union rate was 69/77 (89.6%). There were no differences between the groups for age, sex, BMI, comorbidities, Su classification, open injury, or mechanism of injury. Multivariate analysis identified risks for nonunion including post-operative malalignment (OR 1.41; CI 1.20-1.64; p<0.001), notching pre-operatively (OR 1.22; CI 1.04-1.42; p=0.012), presence of screws through fracture line (OR 1.28; CI 1.17-1.39; p<0.001), plate length <12 holes (OR 1.16; CI 1.02-1.33; p=0.024) and screw density greater than 0.4 (OR 2.18; CI 1.25-3.78; p=0.006). Conclusion. The reoperation rate to promote union was 10.4%. The study identified post-operative malalignment, notching pre-operatively, presence of screws through fracture line, plate length <12 holes, and proximal screw density greater than 40% as independent risk factors for nonunion

Trochlear dysplasia is a specific morphotype of the knee, characterized by but not limited to a specific anatomy of the trochlea. The notch, posterior femur and tibial plateau also seem to be involved. In our study we conducted a semi-automated landmark-based 3D analysis on the distal femur, tibial plateau and patella. The knee morphology of a study population (n=20), diagnosed with trochlear dysplasia and a history of recurrent patellar dislocation was compared to a gender- and age-matched control group (n=20). The arthro-CT scan-based 3D-models were isotropically scaled and landmark-based reference planes were created for quantification of the morphometry. Statistical analysis was performed to detect shape differences between the femur, tibia and patella as individual bone models (Mann-Whitney U test) and to detect differences in size agreement between femur and tibia (Pearson's correlation test). The size of the femur did not differ significantly between the two groups, but the maximum size difference (scaling factor) over all cases was 35%. Significant differences were observed in the trochlear dysplasia (TD) versus control group for all conventional parameters. Morphometrical measurements showed also significant differences in the three directions (anteroposterior (AP), mediolateral (ML), proximodistal (PD)) for the distal femur, tibia and patella. Correlation tests between the width of the distal femur and the tibial plateau revealed that TD knees show less agreement between femur and tibia than the control knees; this was observed for the overall width (TD: r=0.172; p=0.494 - control group: r=0.636; p=0.003) and the medial compartment (TD: r=0.164; p=0.516 - control group: r=0.679; p=0.001), but not for the lateral compartment (TD: r=0.512; p=0.029 - control: r=0.683; p=0.001). In both groups the intercondylar eminence width was strongly correlated with the notch width (TD: r=0.791; p=0.001 - control: r=0.643; p=0.002). The morphology of the trochleodysplastic knee differs significantly from the normal knee by means of an increased ratio of AP/ML width for both femur and tibia, a smaller femoral notch and a lack of correspondence in mediolateral width between the femur and tibia. More specifically, the medial femoral condyle shows no correlation with the medial tibial plateau

Abstract. Background/Objectives. The incidence of reverse total shoulder replacement (rTSR) implantation is increasing globally, but apprehension exists regarding complications and associated challenges. We retrospectively analysed the senior author's series of rTSR from a tertiary centre using the VAIOS shoulder system, a modular 4th generation implant. We hypothesised that the revision rTSR cohort would have less favourable outcomes and more complications. Methods. 114 patients underwent rTSR with the VAIOS system, over 7 years. The primary outcome was implant survival. Secondary outcomes were Oxford shoulder scores (OSS), radiographic analysis (scapular notching, tuberosity osteolysis, and periprosthetic radiolucent lines) and complications. Results. There were 55 Primary rTSR, 31 Revision rTSR and 28 Trauma rTSR. Implant survival: Primary rTSR- 0 revisions, average 3.35-year follow-up. Revision rTSR-1 revision (4.17%), average 3.52-year follow-up. Trauma rTSR- 1 revision (3.57%), average 4.56-year follow-up OSS: Average OSS improved from 15.39 to 33.8 (Primary rTSR) and from 15.11 to 29.1 (Revision rTSR). Average post-operative OSS for the Trauma rTSR was 31.4 Radiological analysis and complications: Low incidence of scapular notching One hairline fracture below the tip of stem, noted incidentally, which required no treatment. One periprosthetic fracture after alcohol related fall. Treated non-surgically One joint infection requiring two-stage revision to rTSR. One dislocation noted at 2 year follow up. This patient had undergone nerve grafting within 6 months of rTSR for axillary nerve injury sustained during the original fracture dislocation. One acromial fracture with tibial and distal humeral fracture after a fall. Conclusions. The 4th generation modular VAIOS implant is a reliable option for various indications. The revision rTSR cohort had favourable outcomes with low complication rates. In this series, early-to-medium term results suggest lower revision rates and good functional outcomes when compared to published reports. We plan to monitor long-term implant survivorship and patient reported outcomes. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Chondral defects in the knee have cartilage biomechanical differences due to defect size and orientation. This study examines how the tibiofemoral contact pressure is affected by increasing full-thickness chondral defect size on the medial and lateral condyle at full extension. Isolated full-thickness, square chondral defects increasing from 0.09cm. 2. to 1.0cm. 2. were created sequentially on the medial and lateral femoral condyles of six human cadaveric knees with intact ligaments and menisci. Chondral defects were created 1.0cm from the femoral notch posteriorly. The knees were fixed to a uniaxial load frame and loaded from 0N to 600N at full extension. Contact pressures between the femoral and tibial condyles were measured using pressure mapping sensors. The peak contact pressure was defined as the highest value in the 2.54mm. 2. area around the defect. The location of the peak contact pressure was determined relative to the centre of the defect. Peak contact pressure was significantly different between (4.30MPa) 0.09cm. 2. and (6.91MPa) 1.0cm. 2. defects (p=0.04) on the medial condyle. On the lateral condyle, post-hoc analysis showed differences in contact pressures between (3.63MPa) 0.09cm. 2. and (5.81MPa) 1.0cm. 2. defect sizes (p=0.02). The location of the stress point shifted from being posteromedial (67% of knees) to anterolateral (83%) after reaching a 0.49cm. 2. defect size (p < 0.01) in the medial condyle. Conversely, the location of the peak contact pressure point moved from being anterolateral (50%) to a posterolateral (67%) location in defect sizes greater than 0.49cm. 2. (p < 0.01). Changes in contact area redistribution and cartilage stress from 0.49cm. 2. to 1.0cm. 2. impact adjacent cartilage integrity. The location of the maximum stress point also varied with larger defects. This study suggests that size cutoffs exist earlier in the natural history of chondral defects, as small as 0.49cm. 2. , than previously studied, suggesting a lower threshold for intervention

Failure of osseointegration and periprosthetic joint infection (PJI) are the two main reasons of implant failure after total joint replacement (TJR). Nanofiber (NF) implant surface coating represents an alternative local drug eluting device that improves osseointegration and decreases the risk of PJI. The purpose of this study was to investigate the therapeutic efficacies of erythromycin (EM)-loaded coaxial PLGA/PCL-PVA NF coating in a rat S. aureus-infected tibia model. NF coatings with 100mg and 1000mg EM were prepared. NF without EM was included as positive control. 56 Sprague Dawley rats were divided into 4 groups. A titanium pin (1.0-mm x 8 mm) was placed into the tibia through the intercondylar notch. S. aureus (SA) was introduced by both direct injection of 10 μl broth (1 × 10. 4. CFU) into the medullary cavity and single dip of Ti pins into a similar solution prior to insertion. Rats were sacrificed at 8 and 16 weeks after surgery. The outcome measurements include μCT based quantitative osteolysis evaluation and hard tissue histology. Results: EM-NF coating (EM100 and EM1000) reduced osteolysis at 8 and 16 weeks, compared to EM0 and negative control. The effective infection control by EM-NFs was further confirmed by hard tissue section analysis. The Bone implant contact (BIC) and bone area fraction Occupancy (BAFO) within 200 µm of the surface of the pins were used to evaluate the osseointegration and new bone formation around the implants. At 16 weeks, the bone implant contact (BIC) of EM 100 (35.08%) was higher than that of negative control (3.43%) and EM0 (0%). The bone area fraction occupancy within 200 µm (BAFO) of EM100 (0.63 mm2) was higher than that of negative control (0.390 mm2) and EM0 (0.0 mm. 2. ). The BAFO of EM100 was also higher than that of EM1000 (0.3mm. 2. ). There was much less osteolysis observed with EM100 and EM1000 NF coatings at 16 weeks, as compared to EM0 positive control, p=0.08 and p=0.1, respectively. Osseointegration and periprosthetic bone formation was enhanced by EM-NFs, especially EM100. Data from this pilot study is promising for improving implant surface fabrication strategies

Abstract. Background. Optimal acetabular component position in Total Hip Arthroplasty is vital for avoiding complications such as dislocation, impingement, abductor muscle strength and range of motion. Transverse acetabular ligament (TAL) and posterior labrum have been shown to be a reliable landmark to guide optimum acetabular cup position. There have been reports of iliopsoas impingement caused by both cemented and uncemented acetabular components. Acetabular component mal-positioning and oversizing of acetabular component are associated with iliopsoas impingement. The Psoas fossa (PF) is not a well-regarded landmark to help with Acetabular Component positioning. Our aim was to assess the relationship of the TAL and PF in relation to Acetabular Component positioning. Methods. A total of 12 cadavers were implanted with the an uncemented acetabular component, their position was initially aligned to TAL. Following optimal seating of the acetabular component the distance of the rim of the shell from the PF was noted. The Acetabular component was then repositioned inside the PF to prevent exposure of the rim of the Acetabular component. This study was performed at Smith & Nephew wet lab in Watford. Results. Out of the twelve acetabular components that were implanted parallel to the TAL, all had the acetabular rim very close or outside to the psoas notch with a potential to cause iliopsoas impingement. Alteration of the acetabular component position was necessary in all cadavers to inside the PF to prevent iliopsoas impingement. It was evident that the edge of PF was not aligned with TAL. Conclusion. Optimal acetabular component position is vital to the longevity and outcome following THA. TAL provides a landmark to guide acetabular component position. We feel the PF is a better landmark to allow appropriate positioning of the acetabular component inside bone without exposure of the component rim and thus preventing iliopsoas impingement at the psoas notch. 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

Abstract. Shoulder replacements have evolved and current 4th generation implants allow intraoperative flexibility to perform anatomic, reverse, trauma, and revision shoulder arthroplasty. Despite high success rates with shoulder arthroplasty, complication rates high as 10–15% have been reported and progressive glenoid loosening remains a concern. Objectives. To report medium term outcomes following 4th generation VAIOS® shoulder replacement. Methods. We retrospectively analysed prospectively collected data following VAIOS® shoulder arthroplasty performed by the senior author between 2014–2020. This included anatomical (TSR), reverse(rTSR), revision and trauma shoulder replacements. The primary outcome was implant survival (Kaplan-Meier analysis). Secondary outcomes were Oxford Shoulder Scores (OSS), radiological outcomes and complications. Results. 172 patients met our inclusion criteria with 114 rTSR, 38 anatomical TSR, and 20 hemiarthroplasty. Reverse TSR- 55 primary, 31 revision, 28 for trauma. Primary rTSR- 0 revisions, average 3.35-year follow-up. Revision rTSR-1 revision (4.17%), average 3.52-year follow-up. Trauma rTSR- 1 revision (3.57%), average 4.56-year follow-up OSS: Average OSS improved from 15.39 to 33.8 (Primary rTSR) and from 15.11 to 29.1 (Revision rTSR). Trauma rTSR-Average post-operative OSS was 31.4 Anatomical TSR38 patients underwent primary anatomical TSR, 8 were revisions following hemiarthroplasty. In 16/38 patients, glenoid bone loss was addressed by bone grafting before implantation of the metal back glenoid component. Mean age at time of surgery was 68.3 years (53 – 81 years). Mean follow-up was 34 months (12 – 62 months). The average Oxford shoulder score improved from 14 (7–30) to 30 (9–48). There were 3 revisions (7.8%); two following subscapularis failure requiring revision conversion to reverse shoulder replacement and one for glenoid graft failure. Conclusions. The medium-term results of the VAIOS® system suggest much lower revision rates across multiple configurations of the system than previously reported, as well as a low incidence of scapular notching. This system allows conversion to rTSR during primary and revision surgery

Introduction and Objective. Local cartilage defects in the knee are painful and mostly followed by arthritis. In order to avoid impaired mobility, the osteochondral defect might be bridged by a synthetic compound material: An osteoconductive titanium foam as an anchoring material in the subchondral bone and an infiltrated polymer as gliding material in contact with the surrounding natural cartilage. Materials and Methods. Titanium foam cylinders (Ø38 mm) with porosities ranging from 57% to 77% were produced by powder metallurgy with two different grain sizes of the space holder (fine: 340 ± 110 μm, coarse: 530 ± 160 μm). The sintered titanium foam cylinders were infiltrated with UHMWPE powder on one end and UHMWPE bulk at the other end, at two different temperatures (160 °C, 200 °C), using a pressure of 20 MPa for 15 minutes. Smaller cylinders (Ø16 mm) were retrieved from the compound material by water jet cutting. The infiltration depths were determined by optical microscopy. The anchoring of the UHMWPE was measured by a shear test and the mechanical properties of the titanium foam were verified by a subsequent compression test. The tribological behaviour was investigated in protein containing liquid using fresh cartilage pins (Ø5 mm) sliding against a UHMWPE disc with or without a notch to simulate the gap between the implant and the surrounding cartilage. Friction coefficients were determined in a rotation tribometer and the cartilage wear in a multidirectional six-station tribometer from AMTI (load 10 – 50 N, sliding speed 20 mm/s, 37 °C). Results. UHMWPE could be infiltrated into titanium foam by 1.1 – 1.3 mm with fine pores and by 1.5 – 1.8 mm with coarse pores. The infiltration was neither dependent on the type of UHMWPE (powder or bulk) nor on the temperature. The polymer was so well anchored inside the titanium foam pores that the shear forces for the compounds exceeded the shear strength obtained for a UHMWPE-cylinder. This effect was due to the increased stiffness of the compound plug. Uniaxial compression of the titanium foams after the shear-off of the polymer revealed yield strengths ranging from 50 – 88 MPa for porosities of 62 – 73%. The Ø16 mm samples yielded beyond physiological loads in the knee (≥ 10x body weight) and behaved in a strain hardening and fully ductile manner, reaching deformations of at least 50 % of their initial height without the appearance of macroscopically visible cracks. For smaller plug diameters down to Ø8 mm, however, the lower porosity / higher strength foam should be used to limit elastic deformation of the compound to < 0.1 mm. Pore size did not significantly influence the strength and stiffness values. The elevated coefficient of friction between cartilage and UHMWPE of about 1 was not negatively affected by the presence of the gap. The height loss of the cartilage pin after 1 hour (respectively after 3600 reciproque wear cycles) was 0.2 ± 0.1 mm using a flat disc. For discs with a 1 mm wide V-notch, the wear increased to 0.9 ± 0.3 mm. Conclusions. The tested titanium foams are well suited to act as an anchoring material in the subchondral bone as mechanical properties can be tailored by choosing the adequate porosity and as bone ingrowth has previously been demonstrated for the used pore sizes. UHMWPE is not an ideal gliding partner against cartilage because the friction coefficients of frictions were high. The presence of a V-notched gap was detrimental for cartilage wear. More hydrophilic polymers like PCU should be tested as potential gliding materials

Reverse total shoulder arthroplasty (RTSA) provides a surgical alternative to conventional shoulder arthroplasty in the rotator cuff deficient shoulder. Short term data has shown consistent improvements in pain and function but higher complication and failure rates have also been reported. The aims of this study were to identify the early and late complications of RTSA, to establish the frequency of glenoid notching, and to assess the post-operative functional outcomes. 21 patients (22 joints) treated with RTSA at Glasgow Royal Infirmary (GRI) between April 2006 and October 2010 were retrospectively reviewed. Indications for surgery included cuff tear arthropathy, revision hemiarthroplasty and fracture malunion. Complication rates were obtained by analysis of follow up data from Bluespier and case notes. Glenoid notching was graded from x-rays by multiple observers using the Sirveaux classification. Outcome was assessed using the Oxford Shoulder Score (OSS) and range of motion (ROM). The complication rate associated with RTSA was 14.3%, effecting 3 patients. One dislocation and 1 ulnar nerve palsy occurred within 30 days post-op. A late complication was represented by 1 dislocation, which required revision. Glenoid notching occurred in 71.4% (15 of 21patients), though the majority had a low Sirveaux classification (grade 1 or 2). OSS increased post-operatively and showed a linear improvement with time (R. 2. = 0.81) and ROM increased significantly post-op compared with pre-op (p<0.001). The complication rate associated with RTSA at GRI was lower than that reported in literature and the outcome was good as defined by ROM and OSS. The rate of glenoid notching was higher than literature reports but the significance of this is unclear as notching may not be associated with loosening

Abstract. Objective. SOX genes comprise a family of transcription factors characterised by a conserved HMG-box domain that confer pleiotropic effects on cell fate and differentiation through binding to the minor groove of DNA. Paracrine regulation and contact-dependant Notch signalling has been suggested to modulate the induction of SOX gene expression. The objective of this study is to investigate the crosstalk between mesenchymal stromal cells (MSCs) and chondrocytes by comparing SOX gene expression in their co-culture and respective monocultures. Methods. Our study adopted an in vitro autologous co-culture of p0 adipose-derived MSCs (AMSCs) and articular chondrocytes derived from Kellgren-Lawrence Grade III/IV osteoarthritic knee joints (n=7). Cells were purified and co-cultured with one AMSC for every chondrocyte at 5000 cells/cm. 2. The AMSCs were characterised by a panel of MSC surface markers in flow cytometry and were allowed to undergo trilineage differentiation for subsequent histological investigation. SOX5, SOX6, and SOX9 expression of co-cultures and monoculture controls were quantified by TaqMan quantitative real-time PCR. Experiments were performed in triplicate. Results. AMSC phenotype was evidenced by the expression of CD105, CD73, CD90 & heterogeneous CD34 but not CD45, CD14, CD19 & HLA-DR in flow cytometry, and also differentiation into chondrogenic, osteogenic and adipogenic lineages with positive Alcian blue, Alizarin Red and Oil Red O staining. The expression of SOX5, SOX6, and SOX9 was greater in observed co-cultures than would be expected from an expression profile modelled from monocultures. Conclusions. These findings provide evidence for the upregulation of SOX family transcription factors expression during the co-culture of MSCs and chondrocytes, suggesting an active induction of chondrogenic differentiation and change of cell fate amidst a microenvironment that facilitates cell-contact and paracrine secretion. This provides insight into the chondrogenic potential and therapeutic effects of MSCs preconditioned by the chondrocyte secretome (or potentially chondrocytes reinvigorated by the MSC secretome), and ultimately, cartilage repair. 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

Image-free navigation technology relies heavily on the surgeon carefully registering bony anatomical landmarks, a critical step in achieving accurate registration which affects the entire procedure. Currently this step may depend on placing a pointer superficially, with soft-tissue and skin obscuring these bony landmarks. We report initial results of using newly developed experimental software which automatically recognises the bone soft-tissue interface. This is the first critical step in development of automatic computer generation of the bone surface topography from ultrasound scanning. Individual 2D ultrasound images (n=651) of the anterior femoral condyles and trochlear notch were used. Images were taken from 29 volunteers (20 male, 9 female). The software extracted bone-soft tissue interface by a two-step method based on a gradient evaluation and the elimination of false-positives with a graph closure. The trochlear notch was automatically defined by geometrical modelisation. Coordinates of both bone interface and trochlear notch position for each separate image were compared to a separate analysis performed manually by a single investigator. Error was calculated using root mean squared (RMS). Median error (RMS) in locating bone soft-tissue interface was 0.67 mm, (mean 0.93 mm, SD 0.84 mm). Median error for trochlear notch topography was 1.01mm, (mean 1.41 mm, SD 1.37 mm). Bone soft-tissue interface can be accurately defined and displayed by this software. Direct visualisation of critical bony landmarks could replace the current comparatively subjective placement of a pointer on superficial tissues. This has powerful application in both non-invasive and surgical computer-assisted acquisition of knee kinematics, and may have further applications in orthopaedic surgery

SOX genes comprise a family of transcription factors characterised by a conserved HMG-box domain that confer pleiotropic effects on cell fate and differentiation through binding to the minor groove of DNA. Paracrine regulation and contact-dependant Notch signalling has been suggested to modulate the induction of SOX gene expression. The objective of this study is to investigate the crosstalk between and preconditioning of mesenchymal stem cells (MSCs) with chondrocytes through comparing SOX gene expression in their co-culture and respective monocultures. Our study adopted an in vitro autologous co-culture of p0 adipose-derived MSCs (AMSCs) and articular chondrocytes derived from Kellgren-Lawrence Grade III/IV osteoarthritic knee joints (n=7). Samples were handled according to the 2004 UK Human Tissue Act. Cells were purified and co-cultured with one AMSC for every chondrocyte at 5000 cells/cm. 2. The AMSCs were characterised by a panel of MSC surface markers in flow cytometry and were allowed to undergo trilineage differentiation for subsequent histological investigation. SOX5, SOX6, and SOX9 expression of co-cultures and monoculture controls were quantified by TaqMan quantitative real-time PCR. Experiments were performed in triplicate. AMSC phenotype was evidenced by the expression of CD105, CD73, CD90 & heterogenous CD34 but not CD45, CD14, CD19 & HLA-DR in flow cytometry, and also differentiation into chondrogenic, osteogenic and adipogenic lineages with positive Alcian blue, Alizarin Red and Oil Red O staining. The expression of SOX5, SOX6, and SOX9 were greater in observed co-cultures than would be expected from an expression profile modelled from monocultures. The findings provides evidence for the upregulation of SOX family transcription factors expression during the co-culture of MSCs and chondrocytes, suggesting an active induction of chondrogenic differentiation and change of cell fate amidst a microenvironment that facilitates cell-contact and paracrine secretion. This provides insight into the chondrogenic potential and therapeutic effects of MSCs preconditioned by the chondrocyte secretome (or potentially chondrocytes reinvigorated by the MSC secretome), and ultimately, cartilage repair

Aim. The aim of this study is to outline the steps and techniques required to create a patient specific 3D printed guide for the accurate placement of the origin of the femoral tunnel for single bundle ACL reconstruction. Introduction. Placements of the femoral tunnels for ACL reconstruction have changed over the years. Most recently there has been a trend towards placing the tunnels in a more anatomic position. There has been subsequent debate as to where this anatomic position should be. The problem with any attempt at consensus over the placement of an anatomic landmark is that each patient has some variation in their positioning and therefore a fixed point for all has compromise for all as it is an average. Our aim was to attempt to make a cost effective and quick custom guide that could allow placement of the center of the patients’ newly created femoral tunnel in the mid position of their contralateral native ACL femoral footprint. Materials & Methods. We took a standard protocol MRI scan of a patient's knee without ACL injury transferred the DICOM files to a personal computer running OsiriX (Pixmeo, Geneva, Switzerland.) and analysed it for a series of specific anatomical landmarks. OsiriX is an image processing software dedicated to DICOM images. We marked the most posterior edge of the articular cartilage on the lateral wall of the notch (1), the most anterior edge of the articular cartilage of the lateral wall of the notch (2), the most inferior edge of the articular cartilage of the lateral wall of the notch (3) and the center of the femoral footprint of the native ACL. Distances were then calculated to determine the position relative to the three articular cartilage points of the center of the ACL footprint. These measurements and points were then utilised to create a 3D computer aided design (CAD) model of a custom guide. This was done using the 3D CAD program 123Design (Autodesk Ltd., Farnbourgh, Hampshire). This 3D model was then exported as an STL file suitable for 3D printing. The STL file was then uploaded to an online 3D printing service and the physical guide was created in transparent acrylic based photopolymer, PA220 plastic and 316L stainless steel. The models created were then measured using vernier calipers to confirm the accuracy of the final guides. Results. The MRI data showed point 1 (AP), point 2 (distal-ACL), point 3 (Ant-ACL) and point 4 (Post-ACL) at a distance of 59.83, 15, 45.8 and 13.9 respectively. For the 3D CAD model, points 1, 2, 3 and 4 were at a distance of 59.83, 15, 45.8 and 13.9 respectively. For the PA220 plastic model, points 1, 2, 3 and 4 were at a distance of 59.86, 14.48, 45.85 and 13.79 respectively. For the 316L stainless steel model, points 1, 2, 3 and 4 were at a distance of 59.79, 14.67, 45.64 and 13.48 respectively. Lastly, for the photopolymer model, points 1, 2, 3 and 4 were at a distance of 59.86, 14.2, 45.4 and 13.69 respectively. The p-value comparing MRI/CAD vs. PA220 was p=0.3753; for the comparison between MRI/CAD vs. 316L, p=0.0683; lastly for the comparison between MRI/CAD Vs. Photopolymer, p=0.3450. The models produced were accurate with no statistical difference in size and positioning of the center of the ACL footprint from the original computer model and to the position of the ACL from the MRI scans. The costs for the models 3D printed were £3.50 for the PA220 plastic, £15 for the transparent photopolymer and £25 for the 316L stainless steel. The time taken from MRI to delivery for the physical models was 7 days. Discussion. Articles regarding the creation of 3D printed custom ACL guides from the patients contralateral knee do not feature in current literature. There has been much research on custom guides for other orthopaedic procedures such as in total knee arthroplasty for the accurate placement of implants. There has also been research published on the creation of custom cutting jigs from CT for complex corrective osteotomy surgery. This study serves as the first step and a proof of concept for the accurate creation of patient specific 3D printed guides for the anatomical placement of the femoral tunnel for ACL reconstruction. The guides were easy to create and produce taking only a week and with a cost of between £3.50 and £25. The design of the guides was to allow the tip of a standard Chondro Pick (Arthrex inc., Naples, Florida.) (3mm) used to mark the starting point of the femoral tunnel to enter through the guide. The next step for this research is to create guides from cadaveric matched knees and utilise the guides to carry out the creation of the femoral tunnels and to analyse of the placement of the tunnel in relation to the contralateral knee

A total of 20 pairs of fresh-frozen cadaver femurs were assigned to four alignment groups consisting of relative varus (10° and 20°) and relative valgus (10° and 20°), 75 composite femurs of two neck geometries were also used. In both the cadaver and the composite femurs, placing the component in 20° of valgus resulted in a significant increase in load to failure. Placing the component in 10° of valgus had no appreciable effect on increasing the load to failure except in the composite femurs with varus native femoral necks. Specimens in 10° of varus were significantly weaker than the neutrally-aligned specimens. The results suggest that retention of the intact proximal femoral strength occurs at an implant angulation of ≥ 142°. However, the benefit of extreme valgus alignment may be outweighed in clinical practice by the risk of superior femoral neck notching, which was avoided in this study

Introduction:. The transverse acetabular ligament (TAL) antomy is not a well explored aspect of the hip joint with limited morphological description in the reviewed literature. It is often used as an anatomical landmark for orientation of the acetabular component in total hip arthroplasty (THA). There is debate as to whether it represents an appropriate guide to cup placement in THA. Present descriptions in orthopaedic literature conside it as a single plane structure to which the surgeon can align the cup. The aim of the current study was to investigate the morphology of the TAL and it was hypothesised that the current description of it being a plane would prove insufficient. Materials and methods:. Seven dry bone hemi-pelves were reconstructed using a microscribe and rhinoceros 4.0 3D software to visualise attachment sites. Three hips from two female donors were dissected to expose the acetabulum and the TAL. This structure was removed and a footprint taken of its perimeter and attachment sites for measurement of ligament length, breadth and area of attachment from digital photographs. Finally, 3D models of the dissected acetabuli with an outline of the TAL and attachment sites were created as before. Results:. The TAL extended beyond the acetabular notch, around the circumference of the acetabular rim. Two attachment sites were identified in each specimen, found at two sites in the superior half of the acetabular rim; one anterior and one posterior. In one specimen, an additional attachment site was identified on the posterior horn. TAL length in each specimen as measured from 2D digital photographs were 132 mm, 117 mm and 179 mm, with attachment areas of 215 mm. 2. , 150 mm. 2. and 350 mm. 2. , respectively. There was marked variation in ligament breadth both between and within individual specimens, ranging from 2.6 to 5.3mm in the smallest specimen and 3.2 to 6.3mm in the largest specimen. The whole structure as one does not conform to be a plane of orientation. Discussion:. Contrary to previous literature assumption, the TAL extended far beyond the acetabular notch. Likewise, its attachment sites were found further round the acetabular rim than previously described. The unexpected breadth may explain the disagreement between studies looking at the structure as an anatomical plane. Further biomechanical research may determine which part – if any – of the ligament, should the acetabular component be orientated to. The details will be presented in the paper