Aim. Periprosthetic joint infections follow 1-3% of arthroplasty surgeries, with the biofilm nature of these infections presenting a significant treatment challenge. 1. Prevention strategies include antibiotic-loaded bone cement; however, increases in cementless procedures means there is an urgent need for alternative local antimicrobial delivery methods. 2. A novel, ultrathin, silica-based sol-gel technology is evaluated in this research as an anti-infective coating for orthopaedic prosthetic devices, providing local antibiotic release following surgery. Method. Reduction in clinically relevant microbial activity and biofilm reduction by antimicrobial sol-gel coatings, containing a selection of antibiotics, were assessed via disc diffusion and microdilution culture assays using the Calgary biofilm device. 3. Proliferation, morphology, collagen, and calcium production by primary bovine osteoblasts cultured upon antibiotic sol-gel surfaces were examined, and cytotoxicity evaluated using Alamar blue staining and lactate dehydrogenase assays. Concentrations of silica, calcium and phosphorus compounds within the cell layer cultured on sol-gel coatings and concentrations eluted into media, were quantified using ICP-OES. Furthermore, cellular phenotype was assessed using alkaline phosphatase activity with time in culture. Results. Low antibiotic concentrations within sol-gel had an inhibitory effect on clinically relevant biofilm growth, for example 0.8 mg ml. -1. tobramycin inhibited clinically isolated S. aureus (MRSA) growth with an 8-log reduction in viable colony forming units. There was no significant difference in metabolic activity between untreated and sol-gel exposed primary bovine osteoblasts in elution-based assays. Reduction (2-fold) in metabolic activity in direct contact assays after 48 hours exposure was likely to be due to increased osteoinduction, whereas no impact upon cell proliferation were observed (p=0.92 at 14 days culture). The morphology of primary osteoblasts was unaffected by culture on sol-gel coatings and collagen production was maintained. Calcium containing nodule production within bovine osteoblastic cells was increased 16-fold after 14 days culture upon sol-gel. Conclusions. The ultrathin sol-gel coating showed low cytotoxicity, strong biofilm reducing activity and antimicrobial activity, which was comparable to antibiotics alone, demonstrating that sol-gel delivery of antibiotics could provide local antimicrobial effects to inhibit PJI growth without the need for bone cement. Future work will develop and evaluate sol-gel performance in an ex vivo explant bone infection model which will reduce the need for animal experimentation

Introduction. Various biomaterials and bone graft substitute technologies for use in osteomyelitis treatment are currently used in clinal practice. They vary in mode of action (with or without antibiotics) and clinical application (one-stage or two-stage surgery). This systematic review aims to compare the clinical evidence of different synthetic antimicrobial bone graft substitutes and antibiotic-loaded carriers in eradicating infection and clinical outcome in patients with chronic osteomyelitis. Methods. Systematic review according to PRISMA statement on publications 2002-2023. MESH terms: osteomyelitis and bone substitutes. FREE terms: chronic osteomyelitis, bone infection. A standardized data extraction form was be used to extract data from the included papers. Results. Publications with increased methodological quality and clinical evidence for biomaterials in osteomyelitis treatment were published in the last decades. High 85-95% eradication rates of osteomyelitis were observed for various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass. Level of evidence varies significantly between products. Antibiotic pharmacokinetic release profiles vary between resorbable Ca-P and/or Ca-S biomaterials. Conclusion. Given the high 85-95% eradication rates of osteomyelitis by various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass, one-stage treatment is preferred. Surgeons should be aware of variations in mechanical properties and antibiotic pharmacokinetic release profiles between Ca-P and CA-s products. Mechanical, biological and antimicrobial properties of bioactive glass are formulation dependent. Currently, only S53P4 bioactive glass has proven antimicrobial properties. Based on this systematic review antibiotic loaded fleeces should be used with caution and restraint

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Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

Introduction. With advances in artificial intelligence, the use of computer-aided detection and diagnosis in clinical imaging is gaining traction. Typically, very large datasets are required to train machine-learning models, potentially limiting use of this technology when only small datasets are available. This study investigated whether pretraining of fracture detection models on large, existing datasets could improve the performance of the model when locating and classifying wrist fractures in a small X-ray image dataset. This concept is termed “transfer learning”. Method. Firstly, three detection models, namely, the faster region-based convolutional neural network (faster R-CNN), you only look once version eight (YOLOv8), and RetinaNet, were pretrained using the large, freely available dataset, common objects in context (COCO) (330000 images). Secondly, these models were pretrained using an open-source wrist X-ray dataset called “Graz Paediatric Wrist Digital X-rays” (GRAZPEDWRI-DX) on a (1) fracture detection dataset (20327 images) and (2) fracture location and classification dataset (14390 images). An orthopaedic surgeon classified the small available dataset of 776 distal radius X-rays (Arbeidsgmeischaft für Osteosynthesefragen Foundation / Orthopaedic Trauma Association; AO/OTA), on which the models were tested. Result. Detection models without pre-training on the large datasets were the least precise when tested on the small distal radius dataset. The model with the best accuracy to detect and classify wrist fractures was the YOLOv8 model pretrained on the GRAZPEDWRI-DX fracture detection dataset (mean average precision at intersection over union of 50=59.7%). This model showed up to 33.6% improved detection precision compared to the same models with no pre-training. Conclusion. Optimisation of machine-learning models can be challenging when only relatively small datasets are available. The findings of this study support the potential of transfer learning from large datasets to improve model performance in smaller datasets. This is encouraging for wider application of machine-learning technology in medical imaging evaluation, including less common orthopaedic pathologies

Introduction. Patients with external fixators are at risk of pin site infection. A more objective assessment of possible pin site infection is warranted, particularly for future home-based monitoring of pin sites. The aim was to determine if thermography can detect signs of inflammation around pin sites by 1) Establishing a maximum temperature cut-off value 2) Investigating the correlation between local temperature and visual signs of inflammation 3) Adjust for anatomical location and ambient room temperature. Method. This was a cross-sectional international multi-center study following STROBE guidelines. All patients with external ring-fixators scheduled for a visit in the out-patient clinic were eligible. Visual signs of inflammation were categorized using the Modified Gordon classification System (MGS, simplified sMGS). Thermographic imaging was done with an infrared camera (FLIR T540) and the maximum temperature within the ROI (MaxTp) was the primary outcome measure. Sample size and reliability were estimated. Cohen-Kappa, ROC-curve/AUC and Poisson regression were used for statistical analysis. Result. Data from 1970 pin sites were included. Inter-rater reliability of MGS was Kappa=0.79 and for MaxTp ICC=0.99 (95%CI: 0.99;0.99). Overall, a tendency of rising temperature with increasing sMGS was seen. The difference between sMGS=0 and sMGS>0 was significant. The performance of MaxTp as a screening tool to detect inflammation was reasonable with an AUC of 0.71 (95% CI: 0.65-0.76). The empirically optimal cut-off value was 34.1°C (Sensitivity=65%, Specificity=72%, Positive predictive value=23%, Negative Predictive value=94%). A 1°C increase in MaxTp increased the RR of visual signs of inflammation by a factor 1.5 (95% CI: 1.3; 1.7). Conclusion. We found a clinical positive association between the temperature at the pin site measured with thermography and visual signs of inflammation. The empirically optimal temperature cut-off value for inflammation screening was 34.1°C. Thermography may be a promising tool for a for a future point of care technology

Introduction. PIEZO mechanoreceptors are increasingly recognized to play critical roles in fundamental physiological processes like proprioception, touch, or tendon biomechanics. However, their gating mechanisms and downstream signaling are still not completely understood, mainly due to the lack of effective tools to probe these processes. Here, we developed new tailor-made nanoswitches enabling wireless targeted actuation on PIEZO1 by combining molecular imprinting concepts with magnetic systems. Method. Two epitopes from functionally relevant domains of PIEZO1 were rationally selected in silico and used as templates for synthesizing molecularly imprinted nanoparticles (MINPs). Highly-responsive superparamagnetic zinc-doped iron oxide nanoparticles were incorporated into MINPs to grant them magnetic responsiveness. Endothelial cells (ECs) and adipose tissue-derived stem cells (ASCs) incubated with each type of MINP were cultured under or without the application of cyclical magnetomechanical stimulation. Downstream effects of PIEZO1 actuation on cell mechanotransduction signaling and stem cell fate were screened by analyzing gene expression profiles. Result. Nanoswitches showed sub-nanomolar affinity for their respective epitope, binding PIEZO1-expressing ECs similarly to antibodies. Expression of genes downstream of PIEZO1 activity significantly changed after magnetomechanical stimulation, demonstrating that nanoswitches can transduce this stimulus directly to PIEZO1 mechanoreceptors. Moreover, this wireless actuation system proved effective for modulating the expression of genes related to musculoskeletal differentiation pathways in ASCs, with RNA-sequencing showing pronounced shifts in extracellular matrix organization, signal transduction, or collagen biosynthesis and modification. Importantly, targeting each epitope led to different signaling effects, implying distinct roles for each domain in the sophisticated function of these channels. Conclusion. This innovative wireless actuation technology provides a promising approach for dissecting PIEZO-mediated mechanobiology and suggests potential therapeutic applications targeting PIEZO1 in regenerative medicine for mechanosensitive tissues like tendon. Acknowledgements. EU's Horizon 2020 ERC under grant No. 772817 and Horizon Europe under grant No. 101069302; FCT/MCTES for PD/BD/143039/2018, COVID/BD/153025/2022, 10.54499/2020.03410.CEECIND/CP1600/CT0013, 10.54499/2022.05526.PTDC, 10.54499/UIDB/50026/2020, 10.54499/UIDP/50026/2020, and 10.54499/LA/P/0050/2020

Introduction. Achieving an appropriate primary stability after implantation is a prerequisite for the long-term viability of a dental implant. Virtual testing of the bone-implant construct can be performed with finite element (FE) simulation to predict primary stability prior to implantation. In order to be translated to clinical practice, such FE modeling must be based on clinically available imaging methods. The aim of this study was to validate an FE model of dental implant primary stability using cone beam computed tomography (CBCT) with ex vivo mechanical testing. Method. Three cadaveric mandibles (male donors, 87-97 years old) were scanned by CBCT. Twenty-three bone samples were extracted from the bones and conventional dental implants (Ø4.0mm, 9.5mm length) were inserted in each. The implanted specimens were tested under quasi-static bending-compression load (cf. ISO 14801). Sample-specific homogenized FE (hFE) models were created from the CBCT images and meshed with hexahedral elements. A non-linear constitutive model with element-wise density-based material properties was used to simulate bone and the implant was considered rigid. The experimental loading conditions were replicated in the FE model and the ultimate force was evaluated. Result. The experimental ultimate force ranged between 67 N and 789 N. The simulated ultimate force correlated better with the experimental ultimate force (R. 2. =0.71) than the peri-implant bone density (R. 2. =0.30). Conclusion. The developed hFE model was demonstrated to provide stronger prediction of primary stability than peri-implant bone density. Therefore, hFE Simulations based on this clinically available low-radiation imaging modality, is a promising technology that could be used in future as a surgery planning tool to assist the clinician in evaluating the load-bearing capacity of an implantation site. Acknowledgements. Funding: EU's Horizon 2020 grant No: 953128 (I-SMarD). Dental implants: THOMMEN Medical AG

Introduction. Kienböck's disease is generally defined as the collapse of the lunate bone, and this may lead to early wrist osteoarthritis. Replacing the collapsed lunate with an implant has regained renewed interest with the advancing technology of additive manufacturing, enabling the design of patient-specific implants. The aims of this project are (1) to determine how accurate it is to use the contralateral lunate shape as a template for patient-specific lunate implants, and (2) to study the effects of shape variations wrist kinematics using 4D-computed tomography (CT) scanning. Methods. A 3D statistical shape model (SSM) of the lunate was built based on bilateral CT scans of 54 individuals. Using SMM, shape variations of the lunate were identified and the intra- and inter-subject shape variations were compared by performing an intraclass correlation analysis. A radiolucent motor-controlled wrist-holder was designed to guide flexion/extension and radial/ulnar deviation of ex vivo wrist specimens under 4D-CT scanning. In this pilot, three shape mode variations were tested per specimen in two specimens were. After post-processing each CT, the scapholunate angle (SLA) and capitolunate angle (CLA) were measured. Results. The shape of the lunate was not symmetrical, defined as exceeding the intra-subject variation in five different shape modes. The FE tests show a generalized increase in scapholunate and capitolunate angle when using lunate implants, and comparing variation of shape modes showed that shape mode 3 has a significant effect on the measured angles (p<0.05). Discussion. The design of patient-specific lunate implants may prove to be challenging using a ‘mirror’-design as it will lead to a degree of shape asymmetry. The pilot study, to determine the effects of those shape variations on wrist kinematics suggest that the degree of shape variation observed indeed may alter the wrist kinematics, although this needs to be further investigated in study using more specimens

Introduction. Cartilage damage is a critical aspect of osteoarthritis progression, but effective imaging strategies remain limited. Consequently, multimodal imaging approaches are receiving increased attention. Gold nanomaterials, renowned for their therapeutic and imaging capabilities, hold promise in drug development. However, their potential for cartilage imaging is rarely discussed. Here, we developed a versatile nanomaterial, AuNC@BSA-Gd-I, for cartilage detection. By leveraging electrostatic interactions with sulfated glycosaminoglycans (sGAG), the AuNC@BSA-Gd-I can effectively penetrate damaged cartilage while accumulating minimally in healthy cartilage. This probe can be visualized or detected using CT, MRI, IVIS, and a gamma counter, providing a comprehensive approach to cartilage imaging. Additionally, we compared the imaging abilities, cartilage visualization capacities, and versatility of currently disclosed multimodal gold nanomaterials with those of AuNC@BSA-Gd-I. Method. The physicochemical properties of nanomaterials were measured. The potential for cartilage visualization of these nanomaterials was assessed using an in vitro porcine model. The sGAG content in cartilage was determined using the dimethylmethylene blue (DMMB) assay to establish the correlation between sGAG concentration and imaging intensity acquired at each modality. Results. The cartilage imaging abilities of AuNC@BSA-Gd-I for CT, MRI, and optical imaging were verified, with each imaging intensity demonstrating a strong correlation with the sGAG content (MRI; R2=0.93, CT; R2=0.83, IVIS; R2=0.79). Furthermore, AuNC@BSA-Gd-. 131. I effectively accumulated in defective cartilage tissue compared to healthy cartilage (23755.38 ± 5993.61 CPM/mg vs. 11699.97 ± 794.93 CPM/mg). Additionally, current gold nanomaterials excelled in individual imaging modalities but lacked effective multimodal imaging ability. Conclusion. Compared to current multimodal gold nanomaterials, AuNC@BSA-Gd-I demonstrates the potential to image cartilage across multiple medical instruments, providing investigators with a more powerful, visible, and convenient approach to detect cartilage defects. Acknowledgements. This work was financially supported by the National Health Research Institute, Taiwan (NHRI-EX112-11029SI), the National Science and Technology Council (NSTC 112-2314-B-182A-105-MY3), and Chang Gung Memorial Hospital, Taiwan (CMRPG8N0781 and CMRPG8M1281-3)

Introduction. The healing of rotator cuff injuries poses significant challenges, primarily due to the complexity of recreating the native tendon-to-bone interface, characterized by highly organized structural and compositional gradients. Addressing this, our innovative approach leverages bioprinted living tissue constructs, incorporating layer-specific growth factors (GFs) to facilitate enthesis regeneration. This method aims to guide in situ zonal differentiation of stem cells, closely mirroring the natural enthesis tissue architecture. Method. Our strategy involves the utilization of advanced bioprinting technology to fabricate living tissue constructs. These constructs are meticulously designed with embedded microsphere-based delivery carriers, ensuring the sustained release of tenogenic, chondrogenic, and osteogenic growth factors. This layer-specific release mechanism is tailored to promote the precise differentiation of stem cells across different regions of the construct, aligning with the gradient nature of enthesis tissues. Result. In vitro studies demonstrated that our layer-specific tissue constructs significantly outperformed basal constructs without GFs, achieving region-specific differentiation of stem cells. More critically, in a rabbit model of rotator cuff tear, these bioprinted living tissue constructs expedited enthesis regeneration. Key outcomes included improved biomechanical properties, enhanced collagen deposition and alignment, and the formation of a gradient fibrocartilage interface with aligned collagen fibrils. After 12 weeks, the constructs achieved an ultimate load failure of 154.3 ± 9.5 N resembling that of native enthesis tissues, marking a notable achievement in tissue engineering. Conclusion. Our exploration introduces a viable and innovative strategy for engineering living tissue constructs that exhibit region-specific differentiation capabilities. This approach holds significant promise for the functional repair of gradient enthesis tissues, potentially revolutionizing the treatment of rotator cuff injuries by closely replicating the natural tendon-to-bone interface, thus offering a promising avenue for future clinical applications

Introduction. Orthopedics is experiencing a significant transformation with the introduction of technologies such as robotics and apps. These, integrated into the post-operative rehabilitation process, promise to improve clinical outcomes, patient satisfaction, and the overall efficiency of the healthcare system. This study examines the impact of an app called Mymobility and intra-operative data collected via the ROSA® robotic system on the functional recovery of patients undergoing robot-assisted knee arthroplasty. Method. The study was conducted at a single center from 2020 to 2023. Data from 436 patients were included, divided into “active” patients (active users of Mymobility) and “non-active” patients. Clinical analyses and satisfaction surveys were carried out on active patients. The intra-operative parameters recorded by ROSA® were correlated with the Patient-Reported Outcome Measures (PROMs) collected via Mymobility. Result. Intra-operative data showed significant correlations with PROMs for the 48 active patients, highlighting the importance of parameters such as medial joint space and ligament laxity. No significant differences were observed between the sexes, but a positive correlation was detected between age and PROMs. The data analysis indicated that an increased medial joint space and reduced ligament laxity are associated with better PROMs. The adoption of Mymobility remained limited, with only 10% of patients fully utilizing the app. Critical factors have been identified to improve recruitment, engagement, and overall experience with the platform. Conclusion. The integration of technologies such as Mymobility and ROSA® in post-operative rehabilitation offers numerous advantages, including the objectification of data, active patient involvement, and personalized care. Challenges remain related to costs, patient compliance, and demographic limitations. Nevertheless, these technologies represent a milestone in modern peri-operative management, being able to improve clinical outcomes and the quality of care

Aims. While residual fixed flexion deformity (FFD) in unicompartmental knee arthroplasty (UKA) has been associated with worse functional outcomes, limited evidence exists regarding FFD changes. The objective of this study was to quantify FFD changes in patients with medial unicompartmental knee arthritis undergoing UKA, and investigate any correlation with clinical outcomes. Methods. This study included 136 patients undergoing robotic arm-assisted medial UKA between January 2018 and December 2022. The study included 75 males (55.1%) and 61 (44.9%) females, with a mean age of 67.1 years (45 to 90). Patients were divided into three study groups based on the degree of preoperative FFD: ≤ 5°, 5° to ≤ 10°, and > 10°. Intraoperative optical motion capture technology was used to assess pre- and postoperative FFD. Clinical FFD was measured pre- and postoperatively at six weeks and one year following surgery. Preoperative and one-year postoperative Oxford Knee Scores (OKS) were collected. Results. Overall, the median preoperative navigated (NAV) FFD measured 6.0° (IQR 3.1 to 8), while the median postoperative NAV FFD was 3.0° (IQR 1° to 4.4°), representing a mean correction of 49.2%. The median preoperative clinical FFD was 5° (IQR 0° to 9.75°) for the entire cohort, which decreased to 3.0° (IQR 0° to 5°) and 2° (IQR 0° to 3°) at six weeks and one year postoperatively, respectively. A statistically significant improvement in PROMs compared with baseline was evident in all groups (p < 0.001). Regression analyses showed that participants who experienced a larger FFD correction, showed greater improvement in PROMs (β = 0.609, p = 0.049; 95% CI 0.002 to 1.216). Conclusion. This study found that UKA was associated with an approximately 50% improvement in preoperative FFD across all three examined groups. Participants with greater correction of FFD also demonstrated larger OKS gains. These findings could prove a useful augment to clinical decision-making regarding candidacy for UKA and anticipated improvements in FFD

Understanding spinopelvic mechanics is important for the success of total hip arthroplasty (THA). Despite significant advancements in appreciating spinopelvic balance, numerous challenges remain. It is crucial to recognize the individual variability and postoperative changes in spinopelvic parameters and their consequential impact on prosthetic component positioning to mitigate the risk of dislocation and enhance postoperative outcomes. This review describes the integration of advanced diagnostic approaches, enhanced technology, implant considerations, and surgical planning, all tailored to the unique anatomy and biomechanics of each patient. It underscores the importance of accurately predicting postoperative spinopelvic mechanics, selecting suitable imaging techniques, establishing a consistent nomenclature for spinopelvic stiffness, and considering implant-specific strategies. Furthermore, it highlights the potential of artificial intelligence to personalize care. Cite this article: Bone Joint J 2024;106-B(11):1206–1215

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The survival of humeral hemiarthroplasties in patients with relatively intact glenoid cartilage could theoretically be extended by minimizing the associated postoperative glenoid erosion. Ceramic has gained attention as an alternative to metal as a material for hemiarthroplasties because of its superior tribological properties. The aim of this study was to assess the in vitro wear performance of ceramic and metal humeral hemiarthroplasties on natural glenoids.

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The objective of this study was to compare simulated range of motion (ROM) for reverse total shoulder arthroplasty (rTSA) with and without adjustment for scapulothoracic orientation in a global reference system. We hypothesized that values for simulated ROM in preoperative planning software with and without adjustment for scapulothoracic orientation would be significantly different.

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The prevalence of obesity is increasing substantially around the world. Elevated BMI increases the risk of complications following total hip arthroplasty (THA). We sought to evaluate trends in BMI and complication rates of obese patients undergoing primary THA over the last 30 years.

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Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials.

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This study aimed to investigate the optimal sagittal positioning of the uncemented femoral component in total knee arthroplasty to minimize the risk of aseptic loosening and periprosthetic fracture.

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This study aims to describe a new method that may be used as a supplement to evaluate humeral rotational alignment during intramedullary nail (IMN) insertion using the profile of the perpendicular peak of the greater tuberosity and its relation to the transepicondylar axis. We called this angle the greater tuberosity version angle (GTVA).