Integrin α2β1 is one of the major transmembrane receptors for fibrillary collagen. In native bone we could show that the absence of this protein led to a protective effect against age-related osteoporosis. The objective of this study was to elucidate the effects of integrin α2β1 deficiency on fracture repair and its underlying mechanisms.

Standardised femoral fractures were stabilised by an intramedullary nail in 12 week old female C57Bl/6J mice (wild type and integrin α2^-/-). After 7, 14 and 28 days mice were sacrificed. Dissected femura were subjected to µCT and histological analyses. To evaluate the biomechanical properties, 28-day-healed femura were tested in a torsional testing device. Masson goldner staining, Alizarin blue, IHC and IF staining were performed on paraffin slices. Blood serum of the animals were measured by ELISA for BMP-2. Primary osteoblasts were analysed by in/on-cell western technology and qRT-PCR.

Integrin α2β1 deficient animals showed earlier transition from cartilaginous callus to mineralized callus during fracture repair. The shift from chondrocytes over hypertrophic chondrocytes to bone-forming osteoblasts was accelerated. Collagen production was increased in mutant fracture callus. Serum levels of BMP-2 were increased in healing KO mice. Isolated integrin deficient osteoblast presented an earlier expression and production of active BMP-2 during the differentiation, which led to earlier mineralisation. Biomechanical testing showed no differences between wild-type and mutant bones.

Knockout of integrin α2β1 leads to a beneficial outcome for fracture repair. Callus maturation is accelerated, leading to faster recovery, accompanied by an increased generation of extra-cellular matrix material. Biomechanical properties are not diminished by this accelerated healing. The underlying mechanism is driven by an earlier availability of BMP-2, one main effectors for bone development. Local inhibition of integrin α2β1 is therefore a promising target to accelerate fracture repair, especially in patients with retarded healing.

In the native articular cartilage microenvironment, chondrocytes are constantly subjected to dynamic physical stimuli that maintains tissue homeostasis. They produce extra cellular matrix (ECM) components such as collagens (type II mainly, 50-75%), proteoglycans (10-30%) and other type of proteins¹ . While collagen offers a large resistance in tension, proteoglycans are the responsible of the viscoelastic response under compression due to the negative charge they confer to the ECM allowing it to entrap a large amount of interstitial fluid. In pathologic states (e.g. osteoarthritis), this ECM is degenerated and the negative charge becomes unbalanced, losing the chondroprotective properties and resulting on an overloaded chondrocytes that further degenerate the matrix.

Low-Intensity Pulsed Ultrasound Stimulation (LIPUS) has been used to generate acoustic (pressure) waves that create bubbles that collapse with cells, inducing a stimulus that can modulate cell response². This mechanical stimulation promotes the expression of type II collagen, type X collagen, aggrecan and TGF-β, appearing as a great strategy to regenerate cartilage. However, current strategies make use of extrinsic forces to stimulate cartilage formation overlooking the physico-chemical properties of the degenerated cartilage, resulting in an excessive load-transfer to chondrocytes and the consequent hypertrophy and degeneration.

Here, interpenetrated networks (IPNs) with different compositions were created using methacrylated gelatin (GelMA), to mimic the collagen, and alginate functionalized with tyramine (Alg-tyr) to mimic glycosaminoglycans and to introduce a negative charge in the model. Within the matrix chondrocytes where encapsulated and stimulated under different conditions to identify the ultrasound parameters that enhance tissue formation. Samples with and without stimulation were compared analysing the expression and deposition of collagen II, aggrecan, collagen X and TGF-β. The results suggested that the chondrogenic marker expression of the samples stimulated for 10 minutes per day for 28 days, was two times higher overall in all of the cases, which was correlated to the tissue formation detected.

Acknowledgments: The authors would like to thank the Basque Government for the “Predoctoral Training Program for Non-Doctoral Research Staff 2021-2022” (Grant ref.: PRE_2021_1_0403). This work was supported by the RETOS grant PID2020-114901RA-I00 of the Ministry of Science and Innovation (MICINN).

Orthopedic Device-Related Infections (ODRIs) are a major medical challenge, particularly due to the involvement of biofilm-encased and multidrug-resistant bacteria. Current treatments, based on antibiotic administration, have proven to be ineffective. Consequently, there is a need for antibiotic-free alternatives. Antimicrobial peptides (AMPs) are a promising solution due to their broad-spectrum of activity, high efficacy at very low concentrations, and low propensity to induce resistance. We aim to develop a new AMP-based chitosan nanogel to be injected during orthopedic device implantation to prevent ODRIs. Chitosan was functionalized with norbornenes (NorChit) through the reaction with carbic anhydride and then, a cysteine-modified AMP, Dhvar5, a peptide with potent antibacterial activity, even against methicillin-resistant Staphylococcus aureus (MRSA), was covalently conjugated to NorChit (NorChit- Dhvar5), through a thiol-norbornene photoclick chemistry (UV= 365 nm). For NorChit-Dhvar5 nanogels production, the NorChit-Dhvar5 solution (0.15% w/v) and Milli-Q water were injected separately into microfluidic system. The nanogels were characterized regarding size, concentration, and shape, using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and Dynamic light scattering (DLS). The nanogels antibacterial properties were assessed in Phosphate Buffer (PBS) for 6 h, against four relevant microorganisms (Pseudomonas aeruginosa, S. aureus and MRSA, and in Muller- Hinton Broth (MHB), 50% (v/v) in PBS, supplemented with human plasma (1% (v/v)), for 6 and 24 h against MRSA. The obtained NorChit-Dhvar5 nanogels, presented a round-shaped and ∼100 nm. NorChit- Dhvar5 nanogels in a concentration of 10¹⁰ nanogels/mL in PBS were capable of reducing the initial inoculum of P. aeruginosa by 99%, S. aureus by 99%, and MRSA by 90%. These results were corroborated by a 99% MRSA reduction, after 24 h in medium. Furthermore, NorChit-Dhvar5 nanogels do not demonstrate signs of cytotoxicity against MC3T3-E1 cells (a pre-osteoblast cell line) after 14 days, having high potential to prevent antibiotic-resistant infection in the context of ODRIs.

Virtual mechanical testing is a method for measuring bone healing using finite element models built from computed tomography (CT) scans. Previously, we validated a dual-zone material model for ovine fracture callus that differentiates between mineralized woven bone and soft tissue based on radiodensity.¹ The objective of this study was to translate the dual-zone material model from sheep to two important clinical scenarios: human tibial fractures in early-stage healing and late-stage nonunions.

CT scans for N = 19 tibial shaft fractures were obtained prospectively at 12 weeks post-op. A second group of N = 33 tibial nonunions with CT scans were retrospectively identified. The modeling techniques were based on our published method.² The dual-zone material model was implemented for humans by performing a cutoff sweep for both the 12-week and nonunion groups. Virtual torsional rigidity (VTR) was calculated as VTR = ML/φ [N-m²/°], where M is the moment reaction, L is the diaphyseal segment length, and φ is the angle of twist.

As the soft tissue cutoff was increased, the rigidity of the clinical fractures decreased and soft tissue located within the fracture gaps produced higher strains that are not predicted without the dual zone approach. The structural integrity of the nonunions varied, ranging from very low rigidities in atrophic cases to very high rigidities in highly calcified hypertrophic cases, even with dual-zone material modeling.

Human fracture calluses are heterogeneous, comprising of woven bone and interstitial soft tissue. Use of a dual-zone callus material model may be instrumental in identifying delayed unions during early healing when callus formation is minimal and/or predominantly fibrous with little mineralization.

Bone regeneration is pivotal for the healing of fractures. In case this process is disturbed a non-union can occur. This can be induced by environmental factors such as smoking, overloading etc. Co-morbidities such as diabetes, osteoporosis etc. may be more intrinsic factors besides other disturbances in the process. Those pathways negatively influence the bone regeneration process. Several intrinsic signal transduction pathways (WNT, BMP etc.) can be affected. Furthermore, on the transcriptional level, important mRNA expression can be obstructed by deregulated miRNA levels. For instance, several miRNAs have been shown to be upregulated during osteoporotic fractures. They are detrimental for osteogenesis as they block bone formation and accelerate bone resorption. Modulating those miRNAs may revert the physiological homeostasis. Indeed, physiological fracture healing has a typical miRNA signature. Besides using molecular pathways for possible treatment of non-union fractures, providing osteogenic cells is another solution. In 5 clinical cases with non-union fractures with defects larger than 10 cm, successful administration of a 3D printed PCL-TCP scaffold with autologous bone marrow aspirate concentrate and a modulator of the pathogenetic pathway has been achieved. All patients recovered well and showed a complete union of their fractures within one year after start of the regenerative treatment.

Thus, non-union fractures are a diverse entity. Nevertheless, there seem to be common pathogenetic disturbances. Those can be counteracted at several levels from molecular to cell. Compositions of those may be the best option for future therapies. They can also be used in a more personalized fashion in case more specific measurements such as miRNA signature and stem cell activity are applied.

Device-associated bacterial infections are a major and costly clinical challenge. This project aimed to develop a smart new biomaterial for implants that helps to protect against infection and inflammation, promote bone growth, and is biodegradable. Gallium (Ga) doped strontium-phosphate was coated on pure Magnesium (Mg) through a chemical conversion process. Mg was distributed in a graduated manner throughout the strontium-phosphate coating GaSrPO4, with a compact structure and a Ga-rich surface. We tested this sample for its biocompatibility, effects on bone remodeling and antibacterial activities including Staphylococcus aureus, S. epidermidis and E. coli - key strains causing infection and early failure of the surgical implantations in orthopaedics and trauma.

Ga was distributed in a gradient way throughout the entire strontium-phosphate coating with a compact structure and a gallium-rich surface. The GaSrPO4 coating protected the underlying Mg from substantial degradation in minimal essential media at physiological conditions over 9 days. The liberated Ga ions from the coatings upon Mg specimens inhibited the growth of bacterial tested. The Ga dopants showed minimal interferences with the SrPO4 based coating, which boosted osteoblasts and undermined osteoclasts in in vitro co-cultures model.

The results evidenced this new material may be further translated to preclinical trial in large animal model and towards clinical trial.

Acknowledgements: Authors are grateful to the financial support from the Australian Research Council through the Linkage Scheme (ARC LP150100343). The authors acknowledge the facilities, and the scientific and technical assistance of the RMIT University and John Curtin School of Medical Research, Australian National University.

The objectives of this study are to evaluate the impact of the CoVID-19 pandemic on the development of relevant emerging digital healthcare trends and to explore which digital healthcare trend does the health industry need most to support HCPs.

A web survey using 39 questions facilitating Five-Point Likert scales was performed from 1.8.2020 – 31.10.2020. Of 260 participants invited, 90 participants answered the questionnaire. The participants were located in the Hospital/HCP sector in 11.9%, in other healthcare sectors in 22.2%, in the pharmaceutical sector in 11.1%, in the medical device and equipment industry in 43.3%. The Five-Point Likert scales were in all cases fashioned as from 1 (strongly disagree) to 5 (strongly agree).

As the top 3 most impacted digital health care trends strongly impacted by CoVID-19, respondents named:

- remote management of patients by telemedicine, mean answer 4.44

- shared data governance under patient control, mean answer 3.80

- new virtual interaction between HCP´s and medical industry, mean answer 3.76

Respondents were asked which level of readiness of the healthcare system currently possess to cope with the current trend impacted by CoVID-19.

- Digital and efficient healthcare logistics, mean answer 1.54

- Integrated health care, mean answer 1.73

- Use of big data and artificial intelligence, mean answer 2.03

Asked if collaborative research in the form of digital data platforms for research data sharing and increasing collaboration with multi-centric consortia would have a positive impact on the healthcare sector, the agreement was high with a value of mean 4.10 on the scale.

We can conclude that the impact of COVID-19 appears to be a high agreement of necessary advances in digitalization in the health care sector and in the collaboration of HCPs with the health care industry. Health care professional are unsure, in how far the national health care sector is capable of transformation in healthcare logistics and integrated health care.

The goal was to analyze the cellular response, specifically the osteogenic capacity, of titanium (Ti) implants harbouring a novel laserbased-surface-structure with the overall aim: augmented osteointegration. Surface micro-/nanoproperties greatly influence cell behaviour at the tissue-implant-interface and subsequent osteointegration. We investigated Ti-materials subjected to a specially developed shifted-Laser-Surface-Texturing (sLST) technology and compared them to a standard roughening-technique (sand-blasting-acid-etching, SLA). The biological response was evaluated with hMSCs, which are naturally available at the bone-implant-interface. We hypothesized: the novel surface is beneficial for our three different (young/healthy-YH; aged/healthy-AH;aged/osteoporotic-OP) cohorts.

The sLST was performed using a SPI-G3-series laser (beam-wavelength=1064nm, pulse-duration=200ns). For the SLA surface, Ti was sandblasted, afterwards acid-etched (HCl/H2SO4). Three different hMSC cohorts were studied: YH: n=6,29±6; AH: n=5,79±5; OP: n=5,76±5 years (osteoporosis confirmed via DEXA-scan). OP hMSCs show e.g. ColI-deficient-matrix and decreased mineralization. Cells were examined for survival, cell proliferation and cytoskeleton arrangement. Osteogenic differentiation was carried out over 21 days, matrix mineralization was validated with Alizarin-Red-S-staining and quantification.

Laser-texturing generated precisely the desired microgeometry. On nanostructural level, differently-sized Ti-droplets were formed stochastically by laser-induced-Ti-plasma. Live/dead-/Actin-stainings showed comparable results for all cohorts and surfaces in terms of survival and cell shape. On Ti-materials, cell growth showed no significant difference between the 3 cohorts. Alizarin quantification revealed the highest levels on laser-textured-surfaces; highest value for YH, followed by AH, lastly OP; no significance between AH/YH, but between OP/YH (p<0.0001). However, mineralization of all cohorts cultured on laser-textured-surfaces increased significantly (p<0.0001) compared to respective SLA-group, with >20fold higher value in the OP-cohort (AH:11fold, YH:6fold).

The data proves the biocompatibility of the laser-structured-Ti for young+aged cohorts. Osteogenic differentiation was significantly augmented on laser-treated-Ti. Most intriguingly, OP-donors could reach manifold increased mineralization, suggesting the novel laser texturing can counteract the osteoporotic phenotype. As osteogenesis-enhancing capacities may be related to mechanisms controlling cellular shape/fate, further investigations referring to this are currently ongoing. In conclusion, our laser-textured-Ti-materials are safe, can have a demand-oriented designer-surface-topography and represent a great potential for development into next-generation-implants suitable for different patient-cohorts, especially osteoporosis patients.

Flat-top talus (FTT) is a complication well-known to those treating clubfoot. Despite varying anecdotal opinions, its association with different treatments, especially the Ponseti method, remains uncertain. This systematic review aimed to establish the aetiology and prevalence of FTT, as well as detailing management strategies and their efficacy.

A systematic review was conducted according to PRISMA guidelines to search for articles using MEDLINE, EMBASE and Web of Science until November 2021. Studies with original data relevant to one of three questions were included: 1) Possible aetiology 2) Prevalence following different treatments 3) Management strategies and their outcomes.

32 original studies were included, with a total of 1473 clubfeet. FTT may be a pre-existing feature of the pathoanatomy of some clubfeet as well as a sequela of treatment. It can be a radiological artefact due to positioning or other residual deformity. The Ponseti method is associated with a higher percentage of radiologically normal tali (57%) than both surgical methods (52%) and non-Ponseti casting (29%). Only one study was identified that reported outcomes after surgical treatment for FTT (anterior distal tibial hemiepiphysiodesis).

The cause of FTT remains unclear. It is seen after all treatment methods but the rate is lowest following Ponseti casting. Guided growth may be an effective treatment.

Key words:

Clubfoot, Flat-top talus, Ponseti method, guided growth

Disclosures: The authors have no relevant disclosures.

Osteoporosis is a common problem in postmenopausal women and the elderly. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates glucocorticoids (GCs) in vivo, which is a considerable potential target as treatment for osteoporosis. Previous studies have demonstrated its effect on osteogenesis, and our study aimed to demonstrate its effect on osteoclast activation.

In vivo, we used 11β-HSD1 knock-off (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, In vivo, We used 11β-HSD1 knockoff (KO) and C57BL6/J mice to undergo the ovariectomy-induced osteoporosis (OVX). In vitro, bone marrow-derived macrophages (BMM) and bone marrow mesenchymal stem cell (BMSC) of KO and C57BL6/J mice were extracted to test their osteogenic and osteoclastic abilities. We then created osteoclastic 11β-HSD1 elimination mice (Ctsk::11β-HSD1fl/fl) and treated them with OVX. Micro-CT analysis, H&E, immunofluorescence staining, and qPCR were performed. Finally, we conducted the high-throughput sequencing to find out 11β-HSD1 and osteoclast activation related genes.

We collected 6w samples after modeling. We found that KO mice were resistant to loss of bone trabeculae. The same effect was observed in osteoclastic 11β-HSD1 elimination mice. Meanwhile, BVT-2733, a classic inhibitor of 11β-HSD1, inhibited the osteoclast effect of cells without affecting osteogenic effect in vitro. High-throughput sequencing suggested that glucocorticoid receptor (GR) may play a key role in the activation of osteoclasts, which was verified by immunofluorescence staining and WB in vivo and in vitro.

In the process of osteoporosis, 11β-HSD1 expression of osteoclasts is abnormally increased, which may be a new target for inhibiting osteoclast activation and treating osteoporosis.

In 2020 almost 90% of femoral heads for total hip implants in Germany were made of ceramic. Nevertheless, the cellular interactions and abrasion mechanisms in vivo have not been fully understood until now. Metal transfer from the head-neck taper connection, occurring as smear or large-area deposit, negatively influences the surface quality of the articulating bearing. In order to prevent metal transfer, damage patterns of 40 Biolox delta ceramic retrievals with CoC and CoPE bearings were analysed.

A classification of damage type and severity for each component (n=40) was done according to an established scoring system. To investigate the physical properties, the surface quality was measured using confocal microscopy, quantitative analysis of phase composition were performed by Raman spectroscopy and qualitative analysis of metal traces was done by scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDX). The periprosthetic tissue was analysed for abrasion particles with SEM and EDX.

Both bearing types show different damage patterns. Dotted/ drizzled metal smears were identified in 82 % of CoC (n=16) and 96 % of CoPE (n=24) bearings. Most traces on the ceramic heads were identified in the proximal area while they were observed predominantly in the distal area for the ceramic inlays. The identified marks are similar to those of metallic bearings. Metallic smears lead to an increase of up to 30 % in the monoclinic crystalline phase of the ceramic. The roughness increases by up to six times to Ra=48 nm. Ceramic and metallic wear particles from the articulating surfaces or head neck taper junctions were found in the periprosthetic tissue.

Damage patterns on CoC hip implants seem to be similar to those of metallic implants. More detailed analysis of CoC implants are needed to understand the described damage patterns and provide advice for prevention.

In 2021 the bone grafting market was worth €2.72 billion globally. As allograft bone has a limited supply and risk of disease transmission, the demand for synthetic grafting substitutes (BGS) continues to grow while allograft bone grafts steadily decrease. Synthetic BGS are low in mechanical strength and bioactivity, inspiring the development of novel grafting materials, a traditionally laborious and expensive process. Here a novel BGS derived from sustainably grown coral was evaluated. Coral-derived scaffolds are a natural calcium carbonate bio-ceramic, which induces osteogenesis in bone marrow mesenchymal stem cells (MSCs), the cells responsible for maintaining bone homeostasis and orchestrating fracture repair. By 3D printing MSCs in coral-laden bioinks we utilise high throughput (HT) fabrication and evaluation of osteogenesis, overcoming the limitations of traditional screening methods.

MSC and coral-laden GelXA (CELLINK) bioinks were 3D printed in square bottom 96 well plates using a CELLINK BIO X printer with pneumatic adapter Samples were non-destructively monitored during the culture period, evaluating both the sample and the culture media for metabolism (PrestoBlue), cytotoxicity (lactose dehydrogenase (LDH)) and osteogenic differentiation (alkaline phosphatase (ALP)). Endpoint, destructive assays used included qRT-PCR and SEM imaging.

The inclusion of coral in the printed bioink was biocompatable with the MSCs, as reflected by maintained metabolism and low LDH release. The inclusion of coral induced osteogenic differentiation in the MSCs as seen by ALP secretion and increased RUNX2, collagen I and osteocalcin transcription.

Sustainably grown coral was successfully incorporated into bioinks, reproducibly 3D printed, non-destructively monitored throughout culture and induced osteogenic differentiation in MSCs. This HT fabrication and monitoring workflow offers a faster, less labour-intensive system for the translation of bone substitute materials to clinic.

Acknowledgements: This work was co-funded by Enterprise Ireland and Zoan Biomed through Innovation Partnership IP20221024.

Our previous research has demonstrated that minor adjustments to in vitro cellular aggregation parameters, i.e. alterations to aggregate size, can influence temporal and spatial mineral depositions within maturing bone cell nodules. What remains unclear, however, is how aggregate size might affect mineralisation within said nodules over long-term in vivo culture.

In this study, we used an osteoblast cell line, MLO-A5, and a primary cell culture, mesenchymal stem cells (MSC), to compare small (approximately 80 µm) with large (approximately 220 µm) cellular aggregates for potential bone nodule development after 8 weeks of culturing in a mouse model (n = 4 each group). In total, 30 chambers were implanted into the intra-peritoneal cavity of 20 male, immunocompromised mice (MF1-Nu/Nu, 4 – 5 weeks old). Nine small or three large aggregates were used per chamber. Neoveil mesh was seeded directly with 2 × 10³ cells for monolayer control. At 8 weeks, the animals were euthanised and chambers fixed with formalin. Aggregate integrity and extracellular material growth were assessed via light microscopy and the potential mineralisation was assessed via micro-CT.

Many large aggregates appeared to disintegrate, whilst the small aggregates maintained their form and produced additional extracellular material with increased sizes. Both MLO-A5 cells and MSC cells saw similar results. Interestingly, however, the MSCs were also seen to produce a significantly higher volume of dense material compared to the MLO-A5 cells from micro-CT analysis.

Overall, a critical cell aggregate size appeared to exist balancing optimal tissue growth with oxygen diffusion, and cell source may influence differentiation pathway despite similar experimental parameters. The MSCs, for example, were likely producing bone via the endochondral ossification pathway, whilst the matured bone cells, MLO-A5 cells, were likely producing bone via the intramembranous ossification pathway.

Acetabular morphology and orientation differs from ethnic group to another. Thus, investigating the normal range of the parameters that are used to assess both was a matter of essence. Nevertheless, the main aim of this study was clarification the relationship between acetabular inclination (AI) and acetabular and femoral head arcs’ radii (AAR and FHAR).

A cross-sectional retrospective study that had been done in a tertiary center where Computed tomography abdomen scouts’ radiographs of non-orthopedics patients were included. They had no history of pelvic or hips’ related symptoms or fractures in femur or pelvis.

A total of 84 patients was included with 52% of them were females. The mean of age was 30.38± 5.48. Also, Means of AI were 38.02±3.89 and 40.15±4.40 (P 0.02, significant gender difference) for males and females, respectively. Nonetheless, Head neck shaft angle (HNSA) means were 129.90±5.55 and 130.72±6.62 for males and females, respectively. However, AAR and FHAR means for males and females were 21.3±3.1mm, 19.9±3.1mm, P 0.04 and 19.7±3.1mm, 18.1±2.7mm, P 0.019, respectively. In addition, negative significant correlations were detected between AI against AAR, FHAR, HNSA and body mass index (BMI) (r 0.529, P ≤0.0001, r 0.445, P ≤0.0001, r 0.238, P 0.029, r 0.329, P ≤0.007, respectively). On the other hand, high BMI was associated with AAR and FHAR (r 0.577, P 0.0001 and r 0.266, p 0.031, respectively).

This study shows that high AI is correlated with lower AAR, FHAR. Each ethnic group has its own normal values that must be studied to tailor the path for future implications in clinical setting.

Mesenchymal stem cells (MSCs) have the potential to repair and regenerate damaged tissues in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. Previous studies suggested that the regenerative activity of stem cells can be enhanced by exposure to tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells-derived mesenchymal-like progenitors (hiPSCs-MPs) can enhance the regenerative potential of human bone marrow mesenchymal stromal cells (hBMSCs).

ECM was engineered from hiPSC-MPs. ECM structure and composition were characterized before and after decellularization using immunofluorescence and biochemical assays. hBMSCs were cultured on the engineered ECM, and differentiated into osteogenic, chondrogenic and adipogenic lineages. Growth and differentiation responses were compared to tissue culture plastic controls.

Decellularization of ECM resulted in efficient cell elimination, as observed in our previous studies. Cultivation hBMSCs on the ECM in osteogenic medium significantly increased hBMSC growth, collagen deposition and alkaline phosphatase activity. Furthermore, expression of osteogenic genes and matrix mineralization were significantly higher compared to plastic controls. Chondrogenic micromass culture on the ECM significantly increased cell growth and expression of chondrogenic markers, including glycosaminoglycans and collagen type II. Adipogenic differentiation of hBMSCs on the ECM resulted in significantly increased hBMSC growth, but significantly reduced lipid vacuole deposition compared to plastic controls. Together, our studies suggest that BMSCs differentiation into osteogenic and chondrogenic lineages can be enhanced, whereas adipogenic activity is decreased by the culture on engineered ECM. Contribution of specific matrix components and underlying mechanisms need to be further elucidated.

Our studies suggest that the three-lineage differentiation of aged BMSCs can be modulated by culture on hiPSC-engineered ECM. Further studies are aimed at scaling-up to three-dimensional ECM constructs for osteochondral tissue regeneration.

The lateral wall thickness (LWT) in trochanteric femoral fractures is a known predictive factor for postoperative fracture stability. Currently, the AO/OTA classification uses a patient non-specific measure to assess the absolute LWT (aLWT) and distinguish stable A1.3 from unstable A2.1 fractures based on a threshold of 20.5 mm. This approach potentially results in interpatient deviations due to different bone morphologies and consequently variations in fracture stability. Therefore, the aim of this study was to explore whether a patient-specific measure for assessment of the relative LWT (rLWT) results in a more precise threshold for prediction of unstable fractures.

Part 1 of the study evaluated 146 pelvic radiographs to assess left-right symmetry with regard to caput-collum-angle (CCD) and total trochanteric thickness (TTT), and used the results to establish the rLWT measurement technique. Part 2 reevaluated 202 patients from a previous study cohort to analyze their rLWT versus aLWT for optimization purposes.

Findings in Part 1 demonstrated a bilateral symmetry of the femur regarding both CCD and TTT (p ≥ 0.827) allowing to mirror bone's morphology and geometry from the contralateral intact to the fractured femur. Outcomes in Part 2 resulted in an increased accuracy for the new determined rLWT threshold (50.5%) versus the standard 20.5 mm aLWT threshold, with sensitivity of 83.7% versus 82.7% and specificity 81.3% versus 77.8%, respectively.

The novel patient-specific rLWT measure can be based on the contralateral femur anatomy and is a more accurate predictor of a secondary lateral wall fracture in comparison to the conventional aLWT. This study established the threshold of 50.5% rLWT as a reference value for prediction of fracture stability and selection of an appropriate implant for fixation of trochanteric femoral fractures.

To analyse bone stresses in humerus-megaprosthesis construct in response to axial loading under varying implant lengths in proximal humeral replacement following tumour excision.

CT scans of 10 cadaveric humeri were processed in 3D Slicer to obtain three-dimensional (3D) models of the cortical and cancellous bone. Megaprostheses of varying body lengths (L) were modelled in FreeCAD to obtain the 3D geometry. Four FE models: group A consisting of intact bone; groups B (L=40mm), C (L=100mm) and D (L=120mm) comprising of humerus-megaprosthesis constructs were created. Isotropic linear elastic behaviour was assigned for all materials. A tensile load of 200N was applied to the elbow joint surface with the glenohumeral joint fixed with fully bonded contact interfaces. Static analysis was performed in Abaqus. The bone was divided at every 5% bone length beginning distally. Statistical analysis was performed on maximum von Mises stresses in cortical and cancellous bone across each slice using one-way ANOVA (0-45% bone length) and paired t-tests (45-70% bone length). To quantify extent of stress shielding, average percentage change in stress from intact bone was also computed.

Maximum stress was seen to occur distally and anteriorly above the coronoid fossa. Results indicated statistically significant differences between intact state and shorter megaprostheses relative to longer megaprostheses and proximally between intact and implanted bones. Varying levels of stress shielding were recorded across multiple slices for all megaprosthesis lengths. The degree of stress shielding increased with implant lengthening being 2-4 times in C and D compared to B.

Axial loading of the humerus can occur with direct loading on outstretched upper limbs or indirectly through the elbow. Resultant stress shielding effect predicted in longer megaprosthesis models may become clinically relevant in repetitive axial loading during activities of daily living. It is recommended to use shorter megaprosthesis to prevent failure.

Stem cell therapy for the intervertebral disc (IVD) is highly debated but holds great promises. From previous studies, it is known that notochordal cells are highly regenerative and may stimulate other differentiated cells to produce more matrix. Lately, a particular tissue-specific progenitor cell population has been identified in the centre of the intervertebral disc (IVD. The current hope is that these nucleus pulposus progenitor cells (NPPC) could play a particular role in IVD regeneration.

Current evidence confirms the presence of these cells in murine, canine, bovine and in the human fetal/surgical samples. Noteworthy, one of the main markers to identify these cells, i.e., Tie2, is a typical marker for endothelial cells. Thus, it is not very clear what their origin and their role might be in the context of developmental biology. In human surgical specimens, their presence is, even more, obscured depending on the donor's age and the condition of the IVD and other yet unknown factors.

Here, I revisit the recent literature on regenerative cells identified for the IVD in the past decades. Current evidence how these NPPC can be isolated and detected in various species and tissues will be recapitulated. Future directions will be provided on how these progenitor cells could be used for regenerative medicine and tissue engineering.

Osteoarthritis (OA) is a degenerative disease that lacks regenerative treatment options. Current research focuses on mesenchymal stem cells (MSCs) and Platelet-Rich Plasma (PRP) as regenerative therapies, but extracellular vesicles (EVs) have shown to be more advantageous. This study compares the regenerative potential of human umbilical cord MSC-derived EVs (cEVs) and platelet-derived EVs (pEVs) in ex vivo and in vivo OA models.

In the ex vivo study, OA conditions were induced in human cartilage explants, which were then treated either with pEVs or cEVs. Results showed a higher content of DNA and collagen in the pEVs group compared to control and cEVs groups, suggesting that pEVs could be a potential alternative to cEVs.

In the in vivo study, an OA model was established in the knee joints of rats through MIA (monoiodoacetate) injection and then treated either with pEVs or cEVs. Results showed that pEVs-treated knee joints had better subchondral bone integrity and greater OA reversion, particularly in female rats, indicating that pEVs are a viable regeneration treatment for OA and outperform cEVs in terms of efficacy.

Overall, the study demonstrates the potential of EVs as a regenerative treatment for OA, with pEVs showing promising results in both ex vivo and in vivo models. The use of pEVs in clinical practice could provide a faster path to translation due to the established use of platelet concentrates in therapeutics. However, further studies are needed to fully evaluate the potential of pEVs for OA treatment and to elucidate the mechanisms behind their regenerative effects.

Acknowledgments: The authors thank Dr Fernando Hierro (UIB) for their technical contribution with TEM, Mª Trinidad García (UIB) for the access to radioactivity facilities, Aina Arbós (IUNICS) for her contribution in the histology staining, María Tortosa (IdISBa) for her assistance with the animal care and ADEMA School of Dentistry for the access to the cone beam computed tomography (CBCT).

Funding: This research was funded by Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, co-funded by the ESF European Social Fund and the ERDF European Regional Development Fund (MS16/00124; CP16/00124), PROGRAMA JUNIOR del proyecto TALENT PLUS, construyendo SALUD, generando VALOR (JUNIOR01/18), financed by the sustainable tourism tax of the Balearic Islands; the Direcció General d'Investigació and Conselleria d'Investigació, Govern Balear (FPI/2046/2017); the Mecanisme de Recuperació i Resiliència, intended to execute research projects of «Noves polítiques públiques per a un mercat de treball dinàmic, resilient i inclusiu», collected in Pla de Recuperació, Transformació i Resiliència, financed by European Union-Next Generation EU and driven by SOIB and Conselleria de Fons Europeus, Universitat i Cultura i la Conselleria de Model Econòmic, Turisme i Treball (NG0421) and the grant SYN20/03 from IdISBa.

To evaluate the functional outcome of open humerus diaphyseal fractures treated with the Three-stitch technique of antegrade humerus nailing.

This is a retrospective study conducted at the Department of Orthopaedics in D. Y. Patil University, School of Medicine, Navi Mumbai, India. The study included 25 patients who were operated on from January 2019 to April 2021 and follow-ups done till May 2022. Inclusion criteria were adult patients with open humerus diaphyseal fractures (Gustilo-Anderson Classification). All patients with closed fractures, skeletally immature patients, and patients with associated head injury were excluded from the study. All patients were operated on with a minimally invasive Three-stitch technique for antegrade humerus nailing. All patients were evaluated based on DASH score.

Out of the 25 patients included in the study, all patients showed complete union. The mean age of the patients was 40.4 years (range 23–66 years). The average period for consolidation of fracture was 10.56 weeks (range 8–14 weeks). The DASH score ranged from 0 to 15.8 with an average score of 2.96. Five patients reported complications with three patients of post-operative infection and delayed wound healing and two patients with screw loosening. All complications were resolved with proper wound care and the complete union was noted. None of the patients had an iatrogenic neurovascular injury.

Three-stitch antegrade nailing technique is a novel method to treat diaphyseal humerus fractures and provides excellent results. It has various advantages such as minimal invasiveness, minimal injury to the rotator cuff, fewer infection rates, minimal iatrogenic injuries, and good functional outcomes. Therefore, this treatment modality can be effectively used for open humerus diaphyseal fractures.

Low back pain affects 80% of the population with half of cases attributed to intervertebral disc (IVD) degeneration. However, the majority of treatments focus on pain management, with none targeting the underlying pathophysiological causes. PCRX-201 presents a novel gene therapy approach that addresses this issue. PCRX-201 codes for interleukin-1 receptor antagonist (IL-1Ra), the natural inhibitor of the pro-inflammatory cytokine IL-1, which orchestrates the catabolic degeneration of the IVD. Our objective here is to determine the ability of PCRX-201 to infect human nucleus pulposus (NP) cells and tissue to increase the production of IL-1Ra and assess downstream effects on catabolic protein production.

Degenerate human NP cells and tissue explants were infected with PCRX-201 at 0 or 3000 multiplicities of infection (MOI) and subsequently cultured for 5 days in monolayer (n=7), 21 days in alginate beads (n=6) and 14 days in tissue explants (n=5). Cell culture supernatant was collected throughout culture duration and downstream targets associated with pain and degeneration were assessed using ELISA.

IL-1Ra production was increased in NP cells and tissue infected with PCRX-201. The production of downstream catabolic proteins such as IL-1β, IL-6, MMP3, ADAMTS4 and VEGF was decreased in both 3D-cultured NP cells and tissue explants.

Here, we have demonstrated that a novel gene therapy, PCRX-201, is able to infect and increase the production of IL-1Ra in degenerate NP cells and tissue in vitro. The increase of IL-1Ra also resulted in a decrease in the production of a number of pro-inflammatory and catabolic proteins, suggesting PCRX-201 enables the inhibition of IL-1-driven IVD degeneration. At present, no treatments for IVD degeneration target the underlying pathology. The ability of FX201 to elicit anti-catabolic responses is promising and warrants further investigation in vitro and in vivo, to determine the efficacy of this exciting, novel gene therapy.

The e-scooter trial was part of a wider initiative from the Department for Transport in response to COVID pandemic. New emergency legislation was introduced in 2020 to make e-scooters legal in the UK for the first time. This scheme was launched in our county from September 2020. The aim of this case series was to identify the types of Orthopedic injuries resultant from electric scooter transport that presented to our District General Hospital over a 16-month period between September 2020 and December 2021.

This study involved retrospective collection of data from electronic hospital records. Data on demographics, laterality, date of injury, type of injury, treatment, HDU/ITU admissions, mortality, and operating time were collected to characterize the types of e-scooter-related injuries and to investigate the frequency of such injuries over the duration of our search.

A total of 79 orthopedic patients identified with electric scooter injuries between September 2020 and December 2021. 78.5% were males and the mean age was 30.1 years. Summer months accounted for most of the injuries. 17 patients required inpatient care. 23 patients required surgical intervention and a total of 29 surgeries were performed in our hospital. This accounted for a total surgical time of 2088 minutes. One patient admitted with shaft of femur fracture developed pulmonary embolism after the definitive operation and died in HDU.

Electric scooters provide a space efficient, affordable, environmentally friendly mode of transportation which reduce the urban congestion and parking issues. This study demonstrates an increasing frequency of significant orthopedic injury associated with e-scooter use treated at our centre over the course of 16 months. This small series underlines an important problem given that this increase has occurred after the start of the electric scooter trial. Legalization might result in further increase in the incidence of injury.

The relationship of degeneration to symptoms has been questioned. MRI detects apparently similar disc degeneration and degenerative changes in subjects both with and without back pain. We aimed to overcome these problems by re-annotating MRIs from asymptomatic and symptomatic groups onto the same grading system.

We analysed disc degeneration in pre-existing large MRI datasets. Their MRIs were all originally annotated on different scales. We re-annotated all MRIs independent of their initial grading system, using a verified, rapid automated MRI annotation system (SpineNet) which reported degeneration on the Pfirrmann (1-5) scale, and other degenerative features (herniation, endplate defects, marrow signs, spinal stenosis) as binary present/absent. We compared prevalence of degenerative features between symptomatics and asymptomatics.

Pfirrmann degeneration grades in relation to age and spinal level were very similar for the two independent groups of symptomatics over all ages and spinal levels. Severe degenerative changes were significantly more prevalent in discs of symptomatics than asymptomatics in the caudal but not the rostral lumbar discs in subjects < 60 years. We found high co-existence of degenerative features in both populations. Degeneration was minimal in around 30% of symptomatics < 50 years.

We confirmed age and disc level are significant in determining imaging differences between asymptomatic and symptomatic populations and should not be ignored. Automated analysis, by rapidly combining and comparing data from existing groups with MRIs and information on LBP, provides a way in which epidemiological and ‘big data’ analysis could be advanced without the expense of collecting new groups.

Prosthetic joint infections represent complications connected to the implantation of biomedical devices, they have high incidence, interfere with osseointegration, and lead to a high societal burden. The microbial biofilm, which is a complex structure of microbial cells firmly attached to a surface, is one of the main issues causing infections. Biofilm- forming bacteria are acquiring more and more resistances to common clinical treatments due to the abuse of antibiotics administration. Therefore, there is increasing need to develop alternative methods exerting antibacterial activities against multidrug-resistant biofilm-forming bacteria. In this context, metal-based coatings with antimicrobial activities have been investigated and are currently used in the clinical practice. However, traditional coatings exhibit some drawbacks related to the insufficient adhesion to the substrate, scarce uniformity and scarce control over the toxic metal release reducing their efficacy. Here, we propose the use of antimicrobial silver-based nanostructured thin films to discourage bacterial infections. Coatings are obtained by Ionized Jet Deposition, a plasma-assisted technique that permits to manufacture films of submicrometric thickness having a nanostructured surface texture, allow tuning silver release, and avoid delamination. To mitigate interference with osseointegration, here silver composites with bone apatite and hydroxyapatite were explored. The antibacterial efficacy of silver films was tested in vitro against gram- positive and gram-negative species to determine the optimal coatings characteristics by assessing reduction of bacterial viability, adhesion to substrate, and biofilm formation. Efficacy was tested in an in vivo rabbit model, using a multidrug-resistant strain of Staphylococcus aureus showing significant reduction of the bacterial load on the silver prosthesis both when coated with the metal only (>99% reduction) and when in combination with bone apatite (>86% reduction). These studies indicate that IJD films are highly tunable and can be a promising route to overcome the main challenges in orthopedic prostheses.

Anterior cruciate ligament reconstruction (ACLR) using a semitendinosus (ST) autograft, with or without gracilis (GR), results in donor muscle atrophy and varied tendon regeneration. The effects of harvesting these muscles on muscle moment arm and torque generating capacity have not been well described. This study aimed to determine between-limb differences (ACLR vs uninjured contralateral) in muscle moment arm and torque generating capacity across a full range of hip and knee motions.

A secondary analysis of magnetic resonance imaging was undertaken from 8 individuals with unilateral history of ST-GR ACLR with complete ST tendon regeneration. All hamstring muscles and ST tendons were manually segmented. Muscle length (cm), peak cross-sectional area (CSA) (cm²), and volume (cm³) were measured in ACLR and uninjured contralateral limbs. OpenSim was used to simulate and evaluate the mechanical consequences of changes in normalised moment arm (m) and torque generating capacity (N.m) between ACLR and uninjured contralateral limbs.

Compared to uninjured contralateral limbs, regenerated ST tendon re-insertion varied proximal (+) (mean = 0.66cm, maximum = 3.44cm, minimum = −2.17cm, range = 5.61cm) and posterior (+) (mean = 0.38cm maximum = 0.71cm, minimum = 0.02cm, range = 0.69cm) locations relative to native anatomical positions. Compared to uninjured contralateral limbs, change in ST tendon insertion point in ACLR limbs resulted in 2.5% loss in peak moment arm and a 3.4% loss in peak torque generating capacity. Accounting for changes to both max isometric force and ST moment arm, the ST had a 14.8% loss in peak torque generating capacity.

There are significant deficits in ST muscle morphology and insertion points following ST-GR ACLR. The ST atrophy and insertion point migration following ACLR may affect force transmission and distribution within the hamstrings and contribute to persistent deficits in knee flexor and internal rotator strength.

Between 2016–2019, 4 patients developed hip infections post-hemiarthroplasty. However, between 2020–2021 (Covid-19 pandemic period), 6 patients developed hip infections following hip hemiarthroplasty.

The purpose of the investigation is to establish the root causes and key learning from the incident and use the information contained within this report to reduce the likelihood of a similar incident in the future. 65 patients presented with a neck of femur fracture during Covid-19 pandemic period between 2020–2021, 26 had hip hemiarthroplasty of which 6 developed hip infections. Medical records, anaesthetic charts and post-hip infections guidelines from RCS and NICE were utilised.

Proteus, Enterococci and Strep. epidermis were identified as the main organisms present causing the hip infection. The average number of ward moves was 4 with 90% of patients developing COVID-19 during their hospital stay. The chance of post-operative wound infection were multifactorial. Having had 5 of 6 patients growing enterococci may suggest contamination of wound either due to potential suboptimal hygiene measures, inadequate wound management /dressing, potential environmental contamination if the organisms (Vancomycin resistant enterococci) are found to be of same types and potential hospital acquired infection due to inadequate infection control measures or suboptimal hand hygiene practices. 3 of the 5 patients grew Proteus, which points towards suboptimal hygiene practices by patients or poor infection control practices by staff.

Lack of maintenance of sterility in post op wound dressings alongside inexperience of the handling of post-operative wound in non-surgical wards; multiple ward transfers exceeding the recommended number according to trust guidelines especially due to pandemic isolation measures and COVID-19 infection itself had resulted in an increased rate of hip infections during the COVID-19 pandemic. Multidisciplinary team education and planned categorisation and isolation strategy is essential to minimise the rate of further hip infections during the pandemic period in future.

Orthopaedic soft tissues, such as tendons, ligaments, and articular cartilage, rely on their unique collagen fiber architectures for proper functionality. When these structures are disrupted in disease or fail to regenerate in engineered tissues, the tissues transform into dysfunctional fibrous tissues. Unfortunately, collagen synthesis in regenerating tissues is often slow, and in some cases, collagen fibers do not regenerate naturally after injury, limiting repair options. One of the research focuses of my team is to develop functional fiber replacements that can promote in vivo repair of musculoskeletal tissues throughout the body. In this presentation, I will discuss our recent advancements in electrowriting 3D printing of natural polymers for creating functional fiber replacements. This manufacturing process utilizes electrical signals to control the flow of polymeric materials through an extrusion nozzle, enabling precise deposition of polymeric fibers with sizes that cannot be achieved using conventional extrusion printing methods. Furthermore, it allows for the formation of fiber organizations that surpass the capabilities of conventional electrospinning processes. During the presentation, I will showcase examples of electrowritten microfiber scaffolds using various naturally-derived polymers, such as gelatin (a denatured form of collagen) and silk fibroin. I will discuss the functional properties of silk-based scaffolds and highlight how they exhibit restored β-sheet and α-helix structures [1]. This restoration results in an elastic response of up to 20% deformation and the ability to withstand cyclic loading without plastic deformation. Additionally, I will present our latest results on the compatibility of this technique with patterning cell-laden fiber structures [2]. This novel biofabrication process allows for the printing of biomimetic microscale architectures with high cell viability, and offers a promising approach to understanding how shear and elongation forces influence cell development of hierarchical (collagen) fibers.

Acknowledgements: The author would like to thank the Reprint project (OCENW.XS5.161) and the program “Materials Driven Regeneration” (024.003.013) by the Netherlands Organization for Scientific Research for the financial support.

Osteoarthritis (OA) and diabetis mellitus type 2 (DMT2) are pathogenetically linked. Complement dysregulation contributes to OA and could be involved in DMT2. The inflammatory anaphylatoxin C5a is released during complement activation. This study aims to understand the specific responses of chondrocytes isolated from diabetic and non-diabetic rats exposed to C5a and/or the proinflammatory cytokine TNFα in vitro dependent on the glucose supply. Articular chondrocytes of adult Zucker Diabetic Fatty (ZDF) rats (homozygous: fa/fa, diabetic, heterozygous: fa/+, lean controls) were exposed to 10 ng/mL TNFα and 25 ng/mL C5a alone or in combination, both, under normo- (NG, 1 g/L glucose) and hyperglycemic (HG, 4.5 g/L glucose) conditions (4 or 24 h). Chondrocyte survival, metabolic activity and gene expression of collagen type 2, suppressors of cytokine signaling (SOCS)1, −3 and anti-oxidative hemoxygenase-1 (HMOX1) were assessed. The complement regulatory protein CD46 and cell nuclei sizes were analyzed. Chondrocyte vitality remained unaffected by the treatment. Metabolic activity was impaired in chondrocytes of non-diabetic rats under HG conditions. Collagen type 2 transcription was suppressed by TNFα under HG condition in chondrocytes from nondiabetic donors and under both conditions in those of DMT2 rats (24 h)

Except for DMT2 chondrocytes under HG (4 h), HMOX1 was generally induced by TNFα +/- C5a (NG, HG). C5a elevated HMOX1 only in chondrocytes of controls. The SOCS1/3 genes were increased by TNFα (NG, diabetic, non diabetic, 4 and 24 h). This could also be observed in chondrocytes of diabetic, but not of lean rats (24 h, HG). At 4 h, C5a induced SOCS1 only in non diabetic chondrocytes (NG, HG). Cytoprotective CD46 protein was suppressed by TNFα under NG condition. Nuclear volumes of chondrocyte were lower in chondrocytes from DMT2 rats compared to those from controls. The differential response suggests that chondrocytes are irreversibly compromised by DMT2.

Achnowledgement: The authors are grateful for the support by the “Stiftung Edoprothetik (S 04/21)”

Intraoperative fractures although rare are one of the complications known to occur while performing a total hip arthroplasty (THA). However, due to lower incidence rates there is currently a gap in this area of literature that systematically reviews this important issue of complications associated with THA.

Method: We looked into Electronic databases including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), the archives of meetings of orthopaedic associations and the bibliographies of included articles and asked experts to identify prospective studies, published in any language that evaluated intra-operative fractures occurring during total hip arthroplasty from the year 1950-2020. The screening, data extraction and quality assessment were carried out by two researchers and if there was any discrepancy, a third reviewer was involved.

Fourteen studies were identified. The reported range of occurrence of fracture while performing hip replacement surgery was found to be 0.4-7.6%. Major risk factors identified were surgical approaches, Elderly age, less Metaphyseal-Diaphyseal Index score, change in resistance while insertion of the femur implants, inexperienced surgeons, uncemented femoral components, use of monoblock elliptical components, implantation of the acetabular components, patients with ankylosing spondylitis, female gender, uncemented stems in patients with abnormal proximal femoral anatomy and with cortices, different stem designs, heterogeneous fracture patterns and toothed design.

Intraoperative fractures during THA were managed with cerclage wire, femoral revision, intramedullary nail and cerclage wires, use of internal fixation plates and screws for management of intra operative femur and acetabular fractures.

The main reason for intraoperative fracture was found to be usage of cementless implants but planning and timely recognition of risk factors and evaluating them is important in management of intraoperative fractures. Adequate surgical site exposure is critical especially during dislocation of hip, reaming of acetabulum, impaction of implant and preparing the femoral canal for stem insertion. Eccentric and increased reaming of acetabulum to accommodate a larger cup is to be avoided, especially in females and elderly patients as the acetabulum is thinner. However, this area requires more research in order to obtain more evidence on effectiveness, safety and management of intraoperative fractures during THA.

This study aims to compare the biomechanical properties of the “Double Lasso-Loop” suture anchor (DLSA) technique with the commonly performed interference screw (IS) technique in an ex vivo ovine model.

Fourteen fresh sheep shoulder specimens were used in this study. Dissection was performed leaving only the biceps muscle attached to the humerus and proximal radius before sharply incised to simulate long head of biceps tendon (LHBT) tear. Repair of the LHBT tear was performed on all specimens using either DSLA or IS technique. Cyclical loading of 500 cycles followed by load to failure was performed on all specimens. Tendon displacement due to the cyclical loading at every 100 cycles as well as the maximum load at failure were recorded and analysed. Stiffness was also calculated from the load displacement graph during load to failure testing.

No statistically significant difference in tendon displacement was observed from 200 to 500 cycles. Statistically significant higher stiffness was observed in IS when compared with DSLA (P = .005). Similarly, IS demonstrated significantly higher ultimate failure load as compared with DSLA (P = .001). Modes of failure observed for DSLA was mostly due to suture failure (7/8) and anchor pull-out (1/8) while IS resulted in mostly LHBT (4/6) or biceps (2/6) tears. DSLA failure load were compared with previous studies and similar results were noted.

After cyclical loading, tendon displacement in DLSA technique was not significantly different from IS technique. Despite the higher failure loads associated with IS techniques in the present study, absolute peak load characteristics of DLSA were similar to previous studies. Hence, DLSA technique can be considered as a suitable alternative to IS fixation for biceps tenodesis.

Bone defects require implantable graft substitutes, especially porous and biodegradable biomaterial for tissue regeneration. The aim of this study was to fabricate and assess a 3D-printed biodegradable hydroxyapatite/calcium carbonate scaffold for bone regeneration.

Conventional 3D printing by itself is incapable of creating pores on a micro scale within deposited filaments throughout 3D scaffolds. These pores and hence larger surface areas are needed for cells to be adhered, proliferated, and differentiated. The aim of this work was to fabricate 3D polycaprolactone (PCL) scaffolds with internal multiscale porosity by using two different 3D printing techniques (ink/pellet of polymer-salt composite in low/high temperature printing) combined with salt leaching to improve cell adhesion, and cell proliferation besides to change degradation rate of PCL scaffolds:

1. Non-solvent phase separation integrated 3D printing of polymer-salt inks with various salt content (i.e., low temperature ink-based printing, LT).

2. FDM printing of composite polymer-salt pellets which will be obtained by casting and evaporating of prepared ink (i.e., high temperature composite-pellet-based printing, HT).

Further, the two approaches were followed by post salt leaching. Stem cells were able to attach on the surface and grow up to 14 days based on increasing cellular activities.

Depletion of Scleraxis-lineage (ScxLin) cells in adult tendon recapitulates age-related decrements in cell density, ECM organization and composition. However, depletion of ScxLin cells improves tendon healing, relative to age-matched wildtype mice, while aging impairs healing. Therefore, we examined whether ScxLin depletion and aging result in comparable shifts in the tendon cell environment and defined the intrinsic programmatic shifts that occur with natural aging, to define the key regulators of age-related healing deficits.

ScxLin cells were depleted in 3M-old Scx-Cre+; Rosa-DTRF/+ mice via diphtheria toxin injections into the hindpaw. Rosa-DTRF/+ mice were used as wildtype (WT) controls. Tendons were harvested from 6M-old ScxLin depleted and WT mice, and 21-month-old (21M) C57Bl/6 mice (aged). FDL tendons (n=6) were harvested for single-cell RNAseq, pooled, collagenase digested, and sorted for single cell capture. Data was processed using Cell Ranger and then aligned to the annotated mouse genome (mm10). Filtering, unsupervised cell clustering, and differential gene expression (DEG) analysis were performed using Seurat.

Following integration and sub-clustering of the tenocyte populations, five distinct subpopulations were observed. In both ScxLin depletion and aging, ‘ECM synthesizers’ and ‘ECM organizers’ populations were lost, consistent with disruptions in tissue homeostasis and altered ECM composition. However, in ScxLin depleted mice retention of a ‘specialized ECM remodeler’ population was observed, while aging tendon cells demonstrated inflammatory skewing with retention of a ‘pro-inflammatory tenocyte population’. In addition, enrichment of genes associated with protein misfolding clearance were observed in aged tenocytes. Finally, a similar inflammatory skewing was observed in aged tendon-resident macrophages, with this skewing not observed in ScxLin depleted tendons.

These data suggest that loss of ‘ECM synthesizer’ populations underpins disruptions in tendon homeostasis. However, retention of ‘specialized remodelers’ promotes enhanced healing (ScxLin depletion), while inflammatory skewing may drive the impaired healing response in aged tendons.

Several synthetic polymers have been widely investigated for their use in bone tissue engineering applications, but the ideal material is yet to be engineered. Triazine-trione (TATO) based materials and their derivatives are novel in the field of biomedical engineering but have started to draw interest. Different designs of the TATO monomers and introduction of different chemical linkages and end-groups widens the scope of the materials due to a range of mechanical properties.

The aim of our work is to investigate novel TATO based materials, with or without hydroxyapatite filler, for their potential in bone tissue engineering constructs. Initially the biocompatibility of the materials was tested, indirectly and directly, according to ISO standards. Following this the osteoconductive properties were investigated with primary osteoblasts and an osteoblastic cell line. Bone marrow derived mesenchymal stem cells were used to evaluate the osteogenic differentiation and consequently the materials potential in bone tissue engineering applications.

Ankle fractures are among the most common types of fractures. If surgery is not performed within 12 to 24 hours, ankle swelling is likely to develop and delay the operative fixation. This leads to patients staying longer in the ward waiting and increased hospital occupancy. This prolonged stay has significant financial implication as well as it is frustrating for both patients and health care professionals.

The aim was to formulate a pathway for the ankle fracture patients coming to the emergency department, outpatients and planned for operative intervention. To identify whether pre-operative hospital admissions of stable ankle fracture patients are reduced with the implementation of the pathway. We formulated an ankle fracture fixation pathway, which was approved for use in December 2020. A retrospective analysis of 6 months hospital admissions of ankle fracture patients in the period between January to June 2020. The duration from admission to the actual surgery was collected to review if some admissions could have been avoided and patients brought directly on the surgery day.

A total of 23 patients were included. Mean age was 60.5 years and SD was 17years. 94% of patients were females. 10 patients were appropriately discharged.7 Patients were appropriately admitted. 6 Patients were unnecessarily admitted. These 6 patients were admitted on presentation to ED. Retrospective analysis of this audit showed that this cohort of patients met the safe discharge criteria and could have been discharged. Duration of unnecessary stay ranged from 1 to 11 days (21 days in total). Total saving could have been £6300.

Standards were met in 74% of cases. Preoperative hospital admission could be reduced with the proposed pathway. It is a valuable tool to be used and should be implemented to reduce unnecessary hospital admissions.

The Royal College of Surgeons of England (RCS) Good Surgical Practice guidance identifies essential criteria for surgical operation note documentation. The current quality improvement project aims to identify if using pre-templated operation notes for documenting fractured neck of femur surgery results in improved documentation when compared to free hand orthopaedic operation notes.

A total of fourteen categories were identified from the RCS guidance as required across all the operations identified in this study. All operations for the month of October 2021 were identified and the operation notes analysed. Pre-templated operation notes were compared to free hand operation notes.

97 cases were identified, of which 74 were free hand operation notes and 23 were pre-templated fractured neck of femur operation notes. All fourteen categories were completed in 13 (57%) of the templated operation notes vs 0 (0%) in the free hand operation notes (odds ratio 0.0052, 95% CI 0.0003 to 0.0945, p < 0.001). The median total number of completed categories was significantly higher in the templated op-note group compared to the free hand op-note group (templated median 14, range 12-14, vs. free hand median 11, range 9 to 13, p < 0.001). Logistic regression analysis of operation notes written by Registrars or Consultants identified Registrars as more likely to document the antibiotic prophylaxis given (p = 0.025).

Use of pre-templated operation notes results in significantly improved documentation. Adoption of generic pre-templated operation notes to improve surgical documentation should be considered across all operations.

Nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is key in maintaining redox homeostasis and the pathogenesis of osteoarthritis (OA) involves oxidative distress. We thus investigated whether Nrf2/ARE signaling may control expression of key chondrogenic differentiation and hyaline cartilage maintenance factor SOX9.

In human C-28/I2 chondrocytes SOX9 expression was measured by RT–qPCR after shRNA-mediated knockdown of Nrf2 or its antagonist the Kelch-like erythroid cell-derived protein with cap “n” collar homology-associated protein 1 (Keap1). Putative ARE-binding sites in the proximal SOX9 promoter region were inactivated, cloned into pGL3, and co-transfected with phRL–TK for dual-luciferase assays to verify whether Nrf2 transcriptionally regulates SOX9. SOX9 promoter activity without and with Nrf2-inducer methysticin were analyzed. Sox9 expression in articular chondrocytes was correlated to cartilage thickness and degeneration in wild-type (WT) and Nrf2-knockout mice. Data were analyzed by one-way ANOVA, a Student's t-test, or Wilcoxon rank-sum test, according to the normal distribution. Statistical significance was set to p < 0.05.

While Keap1-specific RNAi increased SOX9 expression, Nrf2-specific RNAi significantly decreased it. Putative ARE sites (ARE₁, ARE₂) were identified in the SOX9 promoter region. ARE₂ mutagenesis significantly reduced SOX9 promoter activity, while truncation of ARE₁ did not. A functional ARE₂ site was thus essential for methysticin-mediated induction of SOX9 promoter activity. Knee cartilage of young Nrf2-knockout mice further revealed significantly fewer Sox9-positive chondrocytes as compared to old Nrf2-knockout animals, which further showed thinner cartilage and more severe cartilage erosion.

Our data suggest that SOX9 expression in articular cartilage is directly Nrf2-dependent and that pharmacological Nrf2 activation may hold potential to diminish age-dependent osteoarthritic changes in knee cartilage through improving protective SOX9 expression.

Electrospinning is an advantageous technique for cartilage tissue engineering (CTE) applications due to its ability to produce nanofibers recapitulating the size and alignment of the collagen fibers present within the articular cartilage superficial zone. Moreover, coaxial electrospinning allows the fabrication of core-shell fibers able to encapsulate and release bioactive molecules in a sustained manner. Kartogenin (KTG) is a small heterocyclic molecule, which was demonstrated to promote the chondrogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells(hBMSCs)[1].

In this work, we developed and evaluated the biological performance of core-shell poly(glycerol sebacate)(PGS)/poly(caprolactone)(PCL) aligned nanofibers (core:PGS/shell:PCL) mimicking the native articular cartilage extracellular matrix(ECM) and able to promote the sustained release of the chondroinductive drug KTG[2].

The produced coaxial aligned PGS/PCL scaffolds were characterized in terms of their structure and fiber diameter, chemical composition, thermal properties, mechanical performance under tensile testing and in vitro degradation kinetics, in comparison to monoaxial PCL aligned fibers and respective non-aligned controls. KTG was incorporated into the core PGS solution to generate core-shell PGS-KTG/PCL nanofibers and its release kinetics was studied by HPLC analysis. KTG-loaded electrospun aligned scaffolds capacity to promote hBMSCs chondrogenic differentiation was evaluated by assessing cell proliferation, typical cartilage-ECM production (sulfated glycosaminiglycans(sGAG)) and chondrogenic marker genes expression in comparison to non-loaded controls. All the scaffolds fabricated showed average fiber diameters within the nanometer-scale and the core-shell structure of the fibers was clearly confirmed by TEM. The coaxial PGS-KTG/PCL nanofibers evidenced a more sustained drug release over 21 days. Remarkably, in the absence of the chondrogenic cytokine TGF-β3, KTG-loaded nanofibers promoted significantly the proliferation and chondrogenic differentiation of hBMSCs, as suggested by the increased cell numbers, higher sGAG amounts and up-regulation of the chondrogenic genes COL2A1, Sox9, ACAN and PRG4 expression. Overall, our results highlight the potential of core-shell PGS-KTG/PCL aligned nanofibers for the development of novel MSC-based CTE strategies.

Acknowledgements: The authors thank FCT for funding through the project InSilico4OCReg (PTDC/EME-SIS/0838/2021) and to institutions iBB (UID/BIO/04565/2020) and Associate Laboratory I4HB (LA/P/0140/2020).

Conventional proximal tibial osteotomy is a widely successful joint-preserving treatment for osteoarthritis; however, conventional procedures do not adequately control the posterior tibial slope (PTS). Alterations to PTS can affect knee instability, ligament tensioning, knee kinematics, muscle and joint contact forces as well as range of motion.

This study primarily aimed to provide a comprehensive investigation of the variables influencing PTS during high tibial osteotomy using a 3D surgical simulation approach. Secondly, it aimed to provide a simple means of implementing the findings in future 3D pre-operative planning and /or clinically.

The influence of two key variables: the gap opening angle and the hinge axis orientation on PTS was investigated using three independent approaches: (1) 3D computational simulation using CAD software to perform virtual osteotomy surgery and simulate the post-operative outcome. (2) Derivation of a closed-form mathematical solution using a generalised vector rotation approach (3) Clinical assessment of synthetically generated x-rays of osteoarthritis patients (n=28; REC reference: 17/HRA/0033, RD&E NHS, UK) for comparison against the theoretical/computational approaches.

The results from the computational and analytical assessments agreed precisely. For three different opening angles (6°, 9° and 12°) and 7 different hinge axis orientations (from −30° to 30°), the results obtained were identical. A simple analytical solution for the change in PTS, ΔP_s, based on the hinge axis angle, α, and the osteotomy opening angle, θ, was derived:

ΔP_s=sin^-1(sin α sin θ)

The clinical assessment demonstrated that the absolute values of PTS, and changes resulting from various osteotomies, matched the results from the two relative prediction methods.

This study has demonstrated that PTS is impacted by the hinge axis angle and the extent of the osteotomy opening angle and provided computational evidence and analytical formula for general use.

Titanium alloys are one of the most used for orthopaedic implants and the fabrication of them by 3D printing technology is a raising technology, which could effectively resolve existing challenges. Surface modification of Ti surfaces is often necessary to improve biocorrosion resistance, especially in inflammatory conditions. Such modification can be made by coatings based on hydrogels, like alginate (Alg) - a naturally occurring anionic polymer. The properties of the hydrogel can be further enhanced with calcium phosphates like octacalcium phosphate (OCP) as a precursor of biologically formed hydroxyapatite. Formed Alg-OCP matrices have a high potential in wound healing, delivery of bioactive agents etc. but their effect on 3D printed Ti alloys performance was not well known.

In this work, Alg-OCP coated 3D printed samples were studied with electrochemical measurements and revealed significant variations of corrosion resistance vs. composition of the coating. The potentiodynamic polarization test showed that the Alg-OCP-coated samples had lower corrosion current density than simple Alg-coated samples. Electrochemical impedance spectroscopy indicated that OCP incorporated hydrogels had also a high value of the Bode modulus and phase angle. Hence Alg-OCP hydrogels could be highly beneficial in protecting 3D printed Ti alloys especially when the host conditions for the implant placement are inflammatory.

AcThis work was supported by the European Union Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Actions GA860462 (PREMUROSA). The authors also acknowledge the access to the infrastructure and expertise of the BBCE – Baltic Biomaterials Centre of Excellence (European Union Horizon 2020 programme under GA857287).

A major obstacle in biofabrication is replicating the organization of the extracellular matrix and cellular patterns found in anisotropic tissues within bioengineered constructs. While magnetically-assisted 3D bioprinting techniques have the potential to create scaffolds that mimic natural biological structures, they currently lack the ability to accurately control the dispersion of magnetic substances within the bioinks without compromising the fidelity of the intended composite. To overcome this dichotomy, the concepts of magnetically- and matrix-assisted 3D bioprinting are combined here. This method preserves the resolution of printed structures by keeping low viscosity bioinks uncrosslinked during printing, which allows for the arrangement of magnetically-responsive microfibers without compromising the structural integrity of the design. Solidification is induced after the microfibers are arranged in the desired pattern. Furthermore, the precise design of these magnetic microfillers permits the utilization of low levels of inorganic materials and weak magnetic field strengths, which reduces the potential risks that may be associated with their use. The effectiveness of this approach is evaluated in the context of tendon tissue engineering, and the results demonstrate that combining the tendons like anisotropic fibrous microstructure with remote magneto-mechanical stimulation during in vitro maturation provides both biochemical and biophysical cues that effectively guide human adipose-derived stem cells towards a tenogenic phenotype In summary, the developed strategy allows the fabrication of anisotropic high-resolution magnetic composites with remote stimulation functionalities, opening new horizons for tissue engineering applications.

Acknowledgments: ERC Grant CoG MagTendon nr 772817, BioChips PoC project nr 10106930, (PD/BD/129403/2017), (CEECIND/01375/2017), (2020.03410.CEECIND), (2022.05526.PTDC), (ED481B2019/025).

Re-rupture rates after rotator cuff repair remain high because of inadequate biological healing at the tendon-bone interface. Single-growth factor therapies to augment healing at the enthesis have so far yielded inconsistent results. An emerging approach is to combine multiple growth factors over a spatiotemporal distribution that mimics normal healing. We propose a novel combination treatment of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1) and parathyroid hormone (PTH) incorporated into a controlled-release tyraminated poly-vinyl-alcohol hydrogel to improve healing after rotator cuff repair. We aimed to evaluate this growth factor treatment in a rat chronic rotator cuff tear model.

A total of 30 male Sprague-Dawley rats underwent unilateral supraspinatus tenotomy. Delayed rotator cuff repairs were then performed after 3 weeks, to allow tendon degeneration that resembles the human clinical scenario. Animals were randomly assigned to: [1] a control group with repair alone; or [2] a treatment group in which the hydrogel was applied at the repair site. All animals were euthanized 12 weeks after rotator cuff surgery and the explanted shoulders were analyzed for biomechanical strength and histological quality of healing at the repair site.

In the treatment group had significantly higher stress at failure (73% improvement, P=0.003) and Young's modulus (56% improvement, P=0.028) compared to the control group. Histological assessment revealed improved healing with significantly higher overall histological scores (10.1 of 15 vs 6.55 of 15, P=0.032), and lower inflammation and vascularity.

This novel combination growth factor treatment improved the quality of healing and strength of the repaired enthesis in a chronic rotator cuff tear model. Further optimization and tailoring of the growth factors hydrogel is required prior to consideration for clinical use in the treatment of rotator cuff tears. This novel treatment approach holds promise for improving biological healing of this clinically challenging problem.

Osteochondromas are benign chondrogenic lesions arising on the external surface of the bone with aberrant cartilage (exostosis) from the perichondral ring that may contain a marrow cavity also. In a few cases, depending on the anatomical site affected, different degrees of edema, redness, paresthesia, or paresis can take place due to simple contact or friction. Also, depending on their closeness to neurovascular structures, the procedure of excision becomes crucial to avoid recurrence. We report a unique case of recurrent osteochondroma of the proximal humerus enclosing the brachial artery which makes for an important case and procedure to ensure that no relapse occurs.

We report a unique case of a 13-year-old female who had presented with a history of pain and recurrent swelling for 5 years. The swelling size was 4.4 cm x 3.7 cm x 4 cm with a previous history of swelling at the same site operated in 2018. CT reports were suggestive of a large well defined broad-based exophytic diaphyseal lesion in the medial side of the proximal humerus extending posteriorly. Another similar morphological lesion measuring approximately 9 mm x 7 mm was noted involving the posterior humeral shaft. The minimal distance between the lesion and the brachial artery was 2 mm just anterior to the posterio-medial growth. Two intervals were made, first between the tumor and the neurovascular bundle and the other between the anterior tumor and brachial artery followed by exostosis and cauterization of the base.

Proper curettage and excision of the tumor was done after dissecting and removing the soft tissue, blood vessels, and nerves so that there were very less chances of relapse. Post-operative X-ray was done and post 6 months of follow-up, there were no changes, and no relapse was observed. Thus, when presented with a case of recurrent osteochondroma of the proximal humerus, osteochondroma could also be in proximity to important vasculature as in this case enclosing the brachial artery. Thus, proper curettage and excision should be done in such cases to avoid recurrence.

The Cochrane Collaboration has produced five new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner These reviews are relevant to a wide range of musculoskeletal specialists, and include reviews in Morton’s neuroma, scoliosis, vertebral fractures, carpal tunnel syndrome, and lower limb arthroplasty.

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Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms.

Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment.

CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies).

CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.

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In a clinical setting, there is a need for simple gait kinematic measurements to facilitate objective unobtrusive patient monitoring. The objective of this study is to determine if a learned classification model's output can be used to monitor a person's recovery status post-TKA.

The gait kinematics of 20 asymptomatic and 17 people with TKA were measured using a full-body Xsens model¹. The experimental group was measured at 6 weeks, 3, 6, and 12 months post-surgery. Joint angles of the ankle, knee, hip, and spine per stride (10 strides) were extracted from the Xsens software (MVN Awinda studio 4.4)¹.

Statistical features for each subject at each evaluation moment were derived from the kinematic time-series data. We normalised the features using standard scaling². We trained a logistic regression (LR) model using L1-regularisation on the 6 weeks post-surgery data2–4.

After training, we applied the trained LR- model to the normalised features computed for the subsequent timepoints. The model returns a score between 0 (100% confident the person is an asymptomatic control) and 1 (100% confident this person is a patient). The decision boundary is set at 0.5.

The classification accuracy of our LR-model was 94.58%. Our population's probability of belonging to the patient class decreases over time. At 12 months post-TKA, 38% of our patients were classified as asymptomatic.

Imaging can provide valuable information about the function of tissues and organs. The capacity for detecting and measuring imaging biomarkers of biological activities, allows for a better understanding of the pathophysiology of any process in the human body, including the musculoskeletal system. This is of particular importance in oncologic, metabolic and rheumatologic diseases, but not limited to these.

In the domain of the musculoskeletal system, functional imaging also means to be able to address biomechanical evaluations.

Weight-bearing imaging and dynamic studies have a prominent role. All imaging techniques (X-rays, CT, MR, ultrasound) are in demand, and offer different applications, specific equipment and novel methods for addressing this.

Functional imaging is also essential to drive minimally invasive treatments – i.e. interventional radiology, and new treatment approaches move together with the advances on imaging guidance methods.

On both the diagnostic and the interventional side, the increasing availability of dedicated equipment and the development of specific imaging methods and protocols greatly helps the transition from research to clinical practice.

Menisci are crucial structures for knee homeostasis: they provide increase of congruence between the articular surfaces of the distal femur and tibial plateau, bear loading, shock absorption, lubrication, and proprioception. After a meniscal lesion, the golden rule, now, is to save as much meniscus as possible: only the meniscus tissue which is identified as unrepairable should be excised and meniscal sutures find more and more indications. Several different methods have been proposed to improve meniscal healing. They include very basic techniques, such as needling, abrasion, trephination and gluing, or more complex methods, such as synovial flaps, meniscal wrapping, or the application of fibrin clots. Basic research of meniscal substitutes has also become very active in the last decades. The features needed for a meniscal scaffold are: promotion of cell migration, it should be biomimetic and biocompatible, it should resist forces applied and transmitted by the knee, it should slowly biodegrade and should be easy to handle and implant. Several materials have been tested, that can be divided into synthetic and biological. The first have the advantage to be manufactured with the desired shapes and sizes and with precise porosity dimension and biomechanical characteristics. To date, the most common polymers are polylactic acid (PGA); poly-(L)-lactic acid (PLLA); poly- (lactic-co-glycolic acid) (PLGA); polyurethane (PU); polyester carbon and polycaprolactone (PCL). The possible complications, more common in synthetic than natural polymers are poor cell adhesion and the possibility of developing a foreign body reaction or aseptic inflammation, leading to alter the joint architecture and consequently to worsen the functional outcomes. The biological materials that have been used over time are the periosteal tissue, the perichondrium, the small intestine submucosa (SIS), acellular porcine meniscal tissue, bacterial cellulose. Although these have a very high biocompatibility, some components are not suitable for tissue engineering as their conformation and mechanical properties cannot be modified. Collagen or proteoglycans are excellent candidates for meniscal engineering, as they maintain a high biocompatibility, they allow for the modification of the porosity texture and size and the adaptation to the patient meniscus shape. On the other hand, they have poor biomechanical characteristics and a more rapid degradation rate, compared to others, which could interfere with the complete replacement by the host tissue. An interesting alternative is represented by hydrogel scaffolds. Their semi-liquid nature allows for the generation of scaffolds with very precise geometries obtained from diagnostic images (i.e. MRI).

Promising results have been reported with alginate and polyvinyl alcohol (PVA). Furthermore, hydrogel scaffolds can be enriched with growth factors, platelet-rich plasma (PRP) and Bone Marrow Aspirate Concentrate (BMAC). In recent years, several researchers have developed meniscal scaffolds combining different biomaterials, to optimize the mechanical and biological characteristics of each polymer. For example, biological polymers such as chitosan, collagen and gelatin allow for excellent cellular interactions, on the contrary synthetic polymers guarantee better biomechanical properties and greater reliability in the degradation time. Three-dimensional (3D) printing is a very interesting method for meniscus repair because it allows for a patient-specific customization of the scaffolds. The optimal scaffold should be characterized by many biophysical and biochemical properties as well as bioactivity to ensure an ECM-like microenvironment for cell survival and differentiation and restoration of the anatomical and mechanical properties of the native meniscus. The new technological advances in recent years, such as 3D bioprinting and mesenchymal stem cells management will probably lead to an acceleration in the design, development, and validation of new and effective meniscal substitutes.

Mechanical failure of spine posterior fixation in the lumbar region Is suspected to occur more frequently when the sagittal balance is not properly restored. While failures at the proximal extremity have been studied in the literature, the lumbar distal junctional pathology has received less attention. The aim of this work was to investigate if the spinopelvic parameters, which characterize the sagittal balance, could predict the mechanical failure of the posterior fixation in the distal lumbar region.

All the spine surgeries performed in 2017-2019 at Rizzoli Institute were retrospectively analysed to extract all cases of lumbar distal junctional pathology. All the revision surgeries performed due to the pedicle screws pull-out, or the breakage of rods or screws, or the vertebral fracture, or the degenerative disc disease, in the distal extremity, were included in the junctional (JUNCT) group. A total of 83 cases were identified as JUNCT group. All the 241 fixation surgeries which to date have not failed were included in the control (CONTROL) group. Clinical data were extracted from both groups, and the main spinopelvic parameters were assessed from sagittal standing preoperative (pre-op) and postoperative (post-op) radiographs with the software Surgimap (Nemaris). In particular, pelvic incidence (PI), sagittal vertical axis (SVA), pelvic tilt (PT), T1 pelvic angle (TPA), sacral slope (SS) and lumbar lordosis (LL) have been measured.

In JUNCT, the main failure cause was the screws pull-out (45%). Spine fixation with 7 or more levels were the most common in JUNCT (52%) in contrast to CONTROL (14%). In CONTROL, PT, TPA, SS and PI-LL were inside the recommended ranges of good sagittal balance. For these parameters, statistically significant differences were observed between pre-op and post-op (p<0.0001, p=0.01, p<0.0001, p=0.004, respectively, Wilcoxon test). In JUNCT, the spinopelvic parameters were out of the ranges of the good sagittal balance and the worsening of the balance was confirmed by the increase in PT, TPA, SVA, PI-LL and by the decrease of LL (p=0.002, p=0.003, p<0.0001, p=0.001, p=0.001, respectively, paired t-test) before the revision surgery. TPA (p=0.003, Kolmogorov-Smirnov test) and SS (p=0.03, unpaired t-test) differed significantly in pre-op between JUNCT and CONTROL. In post-op, PI-LL was significantly different between JUNCT and CONTROL (p=0.04, unpaired t-test). The regression model of PT vs PI was significantly different between JUNCT and CONTROL in pre-op (p=0.01, Z-test).

These results showed that failure is most common in long fused segments, likely due to long lever arms leading to implant failure. If the sagittal balance is not properly restored, after the surgery the balance is expected to worsen, eventually leading to failure: this effect was confirmed by the worsening of all the spinopelvic parameters before the revision surgery in JUNCT. Conversely, a good sagittal balance seems to avoid a revision surgery, as it is visible is CONTROL. The mismatch PI-LL after the fixation seems to confirm a good sagittal balance and predict a good correction. The linear regression of PT vs PI suggests that the spine deformity and pelvic conformation could be a predictor for the failure after a fixation.

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Hamstring tendons (HT) represent a widely used autograft for ACL reconstruction. Harvesting, processing and pretensioning procedures together with the time out of the joint could theoretically hamper tendon cells (TCs) viability. The authors hypothesize that HT cells are not impaired at the end of the surgical procedures and their tenogenic phenotype may be strongly improved by exposure to PEMF.

Biomedical imaging is essential in the diagnosis of musculoskeletal pathologies and postoperative evaluations. In this context, Cone-Beam technology-based Computed Tomography (CBCT) can make important contributions in orthopaedics. CBCT relies on divergent cone X-rays on the whole field of view and a rotating source-detector element to generate three-dimensional (3D) volumes. For the lower limb, they can allow acquisitions under real loading conditions, taking the name Weight-Bearing CBCT (WB-CBCT). Assessments at the foot, ankle, knee, and at the upper limb, can benefit from it in situations where loading is critical to understanding the interactions between anatomical structures. The present study reports 4 recent applications using WB-CBCT in an orthopaedic centre.

Patient scans by WB-CBCT were collected for examinations of the lower limb in monopodal standing position. An initial volumetric reconstruction is obtained, and the DICOM file is segmented to obtain 3D bone models. A reference frame is then established on each bone model by virtual landmark palpation or principal component analysis. Based on the variance of the model point cloud, this analysis automatically calculates longitudinal, vertical and mid-lateral axes. Using the defined references, absolute or relative orientations of the bones can be calculated in 3D.

In 19 diabetic patients, 3D reconstructed bone models of the foot under load were combined with plantar pressure measurement. Significant correlations were found between bone orientations, heights above the ground, and pressure values, revealing anatomic areas potentially prone to ulceration. In 4 patients enrolled for total ankle arthroplasty, preoperative 3D reconstructions were used for prosthetic design customization, allowing prosthesis-bone mismatch to be minimized. 20 knees with femoral ligament reconstruction were acquired with WB-CBCT and standard CT (in unloading). Bone reconstructions were used to assess congruency angle and patellar tilt and TT-TG. The values obtained show differences between loading and unloading, questioning what has been observed so far. Twenty flat feet were scanned before and after Grice surgery. WB-CBCT allowed characterization of the deformity and bone realignment after surgery, demonstrating the complexity and multi-planarity of the pathology.

These applications show how a more complete and realistic 3D geometric characterization of the of lower limb bones is now possible in loading using WB-CBCT. This allows for more accurate diagnoses, surgical planning, and postoperative evaluations, even by automatisms. Other applications are in progress.

Introduction:

Most of the published papers on AI based diagnosis have focused on the algorithm's diagnostic performance in a ‘binary’ setting (i.e. disease vs no disease). However, no study evaluated the actual value for the clinicians of an AI based approach in diagnostic. Detection of Traumatic thoracolumbar (TL) fractures is challenging on planar radiographs, resulting in significant rates of missed diagnoses (30-60%), thus constituting a field in which a performance improvement is needed. Aim of this study is therefore to evaluate the value provided by AI generated saliency maps (SM), i.e. the maps that highlight the AI identified region of interests.

Scoliosis correction surgery is one of the longest and most complex procedures of all orthopedic surgery. The complication rate is therefore not negligible and is particularly high when the surgery is performed in patients with neuromuscular or connective tissue disease or complex genetic syndromes. In fact, these patients have various comorbidities and organ deficits (respiratory capacity, swallowing / nutrition, heart function, etc.), which can compromise the outcome of the surgery. In these cases, an accurate assessment and preparation for surgery is essential, also making use of external consultants. To make this phase simpler, more effective and homogeneous, a multidisciplinary path of peri-operative optimization is being developed in our Institute, which also includes the possibility of post-operative hospitalization for rehabilitation and recovery. The goal is to improve the basic functional status as much as possible, in order to ensure faster functional recovery and minimize the incidence of peri-operative complications, to be assessed by clinical audit. The path model and the preliminary results on the first patients managed according to the new modality are presented here.

The multidisciplinary path involves the execution of the following assessments / interventions: • Pediatric visit with particular attention to the state of the upper airways and the evaluation of chronic or frequent inflammatory states • Cardiological Consultation with Echocardiogram. • Respiratory Function Tests, Blood Gas Analysis and Pneumological Consultation to evaluate indications for preoperative respiratory physiotherapy cycles, Non-Invasive Ventilation (NIV) cycles, Cough Machine. Possible Polysomnography. • Nutrition consultancy to assess the need for nutritional preparation in order to improve muscle trophism. • Consultation of the speech therapist in cases of dysphagia for liquids and / or solids. • Electroencephalogram and Neurological Consultation in epileptic patients. • Physiological consultation in patients already being treated with a cough machine and / or NIV. • Availability of postoperative hospitalization in the rehabilitation center (with skills in respiratory and neurological rehabilitation) for the most complex cases. When all the appropriate assessments have been completed, the anesthetist in charge at our Institute examines the clinical documentation and establishes whether the path can be considered complete and whether the patient is ready for surgery. At the end of the surgery, the patient is admitted to the Post-operative Intensive Care Unit of the Institute. If necessary, a new program of postoperative rehabilitation (respiratory, neuromotor, etc.) is programmed in a specialist reference center.

To date, two patients have been referred to the preoperative optimization path: one with Ullrich Congenital Muscular Dystrophy, and one with 6q25 Microdeletion Syndrome. In the first case, the surgery was performed successfully, and the patient was discharged at home. In the second case, after completing the optimization process, the surgery was postponed due to the finding of urethral malformation with the impossibility of bladder catheterization, which made it necessary to proceed with urological surgery first.

The preliminary case series presented here is still very limited and does not allow evaluations on the impact of the program on the clinical practice and the complication rate. However, these first experiences made it possible to demonstrate the feasibility of this complex multidisciplinary path in which a network of specialists takes part.

Low back pain (LBP) is the leading cause of disability worldwide. Recently, treatment of the intervertebral disc (IVD) with stem cells has been used for the treatment of degenerate discs (IDD) which cause at least the 40% of LBP cases. Despite pain reduction, follow-up in clinical studies have not shown an improvement in the structural integrity of IVD. A valid alternative could be the use of progenitor disc cells (notocordal cells, NC) or of their precursors. Mesendoderm progenitor cells (MEPC) have the ability to replicate and differentiate toward NC. In this preliminary study we evaluated in a preclinical large animal IDD model the viability and NC differentiation of MEPC derived from induced pluripotent stem cells (iPSC).

MEPC, derived from iPSC and developed during the iPSpine project (# 825925), were thawed and plated on laminin for 24h and labeled with PKH26.

Two adult sheep were subjected to nucleotomy of five lumbar discs for the induction of IDD. After 5 weeks, 3 of the 5 degenerate discs were treated with MEPC at 3 different doses (low, medium and high). One sheep was sacrificed after 7 days and the other after 30 days from the treatment injection procedure. Clinical parameters were collected to evaluate the safety of treatment. Discs were paraffin embedded and analysed using histological techniques. Survival (PKH26), proliferation (PCNA), notocordal cell differentiation (Brachyury, Cytokeratin 8/18/19, Sox9, Foxa2) and endodermal differentiation (Sox17) were evaluated.

After the injection of the cells, both sheep lost about 20% of body weight. The analysis showed that only in discs treated with the highest dose the PKH26 stained cells resulted alive after 30 days from the procedure. These cells turn out to be:

This preliminary study shows that MEPC, derived from iPSC and injected into ovine discs degenerated by nucleotomy, are able to survive 30 days from treatment and differentiate within the disc predominantly towards the notocordal phenotype.

Abstract

Cranial cruciate ligament (CrCL) disease/rupture is a highly prevalent orthopaedic disease in dogs and common cause of pain, lameness, and secondary joint osteoarthritis (OA). Previous experiments investigating the role of glutamate receptors (GluR) in arthritic degeneration and pain revealed that OA biomarkers assessing early bone turnover and inflammation, including osteoprotegerin (OPG) and the receptor activator of nuclear factor kappa-B ligand (RANKL) are more likely to be influenced by glutamate signalling. Moreover, interleukin-6 (IL-6) has a complex and potentially bi directional (beneficial and detrimental) effect, and it is a critical mediator of arthritic pain, OA progression and joint destruction.

Abstract

There is no consensus on how to evaluate and grade pin site infection. A precise, objective and reliable pin site infectious score is warranted. The literature was reviewed for pin site infection classification systems, The Modified Gordon Score (MGS) grade 0-6 was used. The aim was to test the reliability of The Modified Gordon Infection Score. The observed agreement and inter-rater reliability were investigated between nurse and doctors.

MGS was performed in the outpatient clinic at Aalborg University Hospital, Denmark on 1472 pin sites in 119 patients by one nurse and one of three orthopaedic surgeons blinded to each other's judgement. The data was stored in a Red Cap Database for further statistical analysis. The observed agreement between the nurse and the 3 orthopaedic surgeons was evaluated with a one-way random-effect model with interclass correlation with absolute agreement. Furthermore the observed agreement for each of the 3 surgeons with the nurse was calculated.

The distribution of MGS infection grade in the 1472 pin sites was: Grade 0; n=1372, Grade 1; n=32, Grade 2; n=39, Grade 3; n=24, Grade 4; n=5, Grade 5; n=0, Grade 6; n=0.

The observed agreement between the nurse and the surgeons was calculated as 98%. The ICC estimated between nurse and the surgeons was 0,8943 (ICC >0,85 = reliable). The grading was done by three different doctors with an agreement with the nurse as follows. Rater1 (n=416) =99,5 %, Rater2 (n=1440) =97,4%, Rater3 (n=1440) =96,6%.

A limitation to this study is that the dataset represents mostly clean pin sites with MGS 0. Only 100 pin sites had signs of superficial infection MGS 1-4 none above 4. We found that the MGS infection score is highly reliable for low grade infections but we cannot conclude on reliability in severe infections.

To detect early signs of infection infrared thermography has been suggested to provide quantitative information. Our vision is to invent a pin site infection thermographic surveillance tool for patients at home. A preliminary step to this goal is the aim of this study, to automate the process of locating the pin and detecting the pin sites in thermal images efficiently, exactly, and reliably for extracting pin site temperatures.

A total of 1708 pin sites was investigated with Thermography and augmented by 9 different methods in to totally 10.409 images. The dataset was divided into a training set (n=8325), a validation set (n=1040), and a test set (n=1044) of images. The Pin Detection Model (PDM) was developed as follows: A You Only Look Once (YOLOv5) based object detection model with a Complete Detection Intersection over Union (CDIoU), it was pre-trained and finetuned by the through transfer learning. The basic performance of the YOLOv5 with CDIoU model was compared with other conventional models (FCOS and YOLOv4) for deep and transition learning to improve performance and precision. Maximum Temperature Extraction (MTE) Based on Region of Interest (ROI) for all pin sites was generated by the model. Inference of MTE using PDM with infected and un-infected datasets was investigated.

An automatic tool that can identify and annotate pin sites on conventional images using bounding boxes was established. The bounding box was transferred to the infrared image. The PMD algorithm was built on YOLOv5 with CDIoU and has a precision of 0.976. The model offers the pin site detection in 1.8 milliseconds. The thermal data from ROI at the pin site was automatically extracted.

These results enable automatic pin site annotation on thermography. The model tracks the correlation between temperature and infection from the detected pin sites and demonstrates it is a promising tool for automatic pin site detection and maximum temperature extraction for further infection studies. Our work for automatic pin site annotation on thermography paves the way for future research on infection assessment using thermography.

Abstract

Fragility ankles fractures in the geriatric population are challenging to manage, due to fracture instability, soft tissue compromise, patient co-morbidities. Traditional management options include open reduction internal fixation, or conservative treatment, both of which are fraught with high complication rates. We aimed to present functional outcomes of elderly patients with fragility ankle fractures treated with tibiotalocalcaneal nails.

171 patients received a tibiotalocalcaneal nail over a six-year period, but only twenty met the inclusion criteria of being over sixty and having poor bone stock, verified by radiological evidence of osteopenia or history of fragility fractures. Primary outcome was mortality risk from co-morbidities, according to the Charlson co-morbidity index (CCI), and patients’ post-operative mobility status compared to pre-operative mobility. Secondary outcomes include intra-operative and post-operative complications, six-month mortality rate, time to mobilisation and union.

The mean age was 77.82 years old, five of whom are type 2 diabetics. The average CCI was 5.05. Thirteen patients returned to their pre-operative mobility state. Patients with low CCI are more likely to return to pre-operative mobility status (p=0.16; OR=4.00).

Average time to bone union and mobilisation were 92.5 days and 7.63 days, respectively. Mean post-operative AOFAS ankle-hindfoot and Olerud-Molander scores were 53.0 (range 17-88) and 50.9 (range 20-85), respectively. There were four cases of broken distal locking screws, and four cases of superficial infection. Patients with high CCI were more likely to acquire superficial infections (p=0.264, OR=3.857). There were no deep infections, periprosthetic fractures, nail breakages, non-unions.

TTC nailing is an effective treatment methodology for low-demand geriatric patients with fragility ankle fractures. This technique leads to low complication rates and early mobilisation. It is not a life-changing procedure, with many able to return to their pre-operative mobility status, which is important for preventing the loss of socioeconomic independence.

Abstract

Mechanical loading of joints with osteoarthritis (OA) results in pain-related functional impairment, altered joint mechanics and physiological nociceptor interactions leading to an experience of pain. However, the current tools to measure this are largely patient reported subjective impressions of a nociceptive impact. A direct measure of nociception may offer a more objective indicator. Specifically, movement-induced physiological responses to nociception may offer a useful way to monitor knee OA. In this study, we gathered preliminary data on healthy volunteers to analyse whether integrated biomechanical and physiological sensor datasets could display linked and quantifiable information to a nociceptive stimulus.

Following ethical approval, 15 healthy volunteers completed 5 movement and stationary activities in 2 conditions; a control setting and then repeated with an applied quantified thermal pain stimulus to their right knee. An inertial measurement unit (IMU) and an electromyography (EMG) lower body marker set were tested and integrated with ground reaction force (GRF) data collection. Galvanic skin response electrodes for skin temperature and conductivity and photoplethysmography (PPG) sensors were manually timestamped to the integrated system.

Pilot data showed EMG, GRF and IMU fluctuations within 0.5 seconds of each other in response to a thermal trigger. Preliminary analysis on the 15 participants tested has shown skin conductance, PPG, EMG, GRFs, joint angles and kinematics with varying increases and fluctuations during the thermal condition in comparison to the control condition.

Preliminary results suggest physiological and biomechanical data outputs can be linked and identified in response to a defined nociceptive stimulus. Study data is currently founded on healthy volunteers as a proof-of-concept. Further exploratory statistical and sensor readout pattern analysis, alongside early and late-stage OA patient data collection, can provide the information for potential development of wearable nociceptive sensors to measure disease progression and treatment effectiveness.

A major cause of morbidity in lower limb amputees is phantom limb pain (PLP) and residual limb pain (RLP). This study aimed to determine if surgical interposition of nerve endings into adjacent muscle bellies at the time of major lower limb amputation can decrease the incidence and severity of PLP and RLP.

Data was retrospectively collected from January 2015 to January 2021, including eight patients that underwent nerve interposition (NI) and 36 that received standard treatment. Primary outcomes included the 11-point Numerical Rating Scale (NRS) for pain severity, and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behaviour, and interference. Secondary outcome included Neuro-QoL Lower Extremity Function assessing mobility. Cumulative scores were transformed to standardised t scores.

Across all primary and secondary outcomes, NI patients had lower PLP and RLP. Mean ‘worst pain’ score was 3.5 out of 10 for PLP in the NI cohort, compared to 4.89 in the control cohort (p=0.298), and 2.6 out of 10 for RLP in the NI cohort, compared to 4.44 in the control cohort (p=0.035). Mean ‘best pain’ and ‘current pain’ scores were also superior in the NI cohort for PLP (p=0.003, p=0.022), and RLP (p=0.018, p=0.134).

Mean PROMIS t scores were lower for the NI cohort for RLP (40.1 vs 49.4 for pain intensity; p=0.014, 44.4 vs 48.2 for pain interference; p=0.085, 42.5 vs 49.9 for pain behaviour; p=0.025). Mean PROMIS t scores were also lower for the NI cohort for PLP (42.5 vs 52.7 for pain intensity; p=0.018); 45.0 vs 51.5 for pain interference; p=0.015, 46.3 vs 51.1 for pain behaviour; p=0.569). Mean Neuro-QoL t score was lower in NI cohort (45.4 vs 41.9;p=0.03).

Surgical interposition of nerve endings during lower limb amputation is a simple yet effective way of minimising PLP and RLP, improving patients’ subsequent quality of life. Additional comparisons with targeted muscle reinnervation should be performed to determine the optimal treatment option.

Evidence supporting the use of virtual reality (VR) training in orthopaedic procedures is rapidly growing. However, the impact of the timing of delivery of this training is yet to be tested. We aimed to investigate whether spaced VR training is more effective than massed VR training.

24 medical students with no hip arthroplasty experience were randomised to learning the direct anterior approach total hip arthroplasty using the same VR simulation, training either once-weekly or once-daily for four sessions. Participants underwent a baseline physical world assessment on a saw bone pelvis. The VR program recorded procedural errors, time, assistive prompts required and hand path length across four sessions. The VR and physical world assessments were repeated at one-week, one-month, and 3 months after the last training session.

Baseline characteristics between the groups were comparable (p > 0.05). The daily group demonstrated faster skills acquisition, reducing the median ± IQR number of procedural errors from 68 ± 67.05 (session one) to 7 ± 9.75 (session four), compared to the weekly group's improvement from 63 ± 27 (session one) to 13 ± 15.75 (session four), p < 0.001. The weekly group error count plateaued remaining at 14 ± 6.75 at one-week, 16.50 ± 16.25 at one-month and 26.45 ± 22 at 3-months, p < 0.05. However, the daily group showed poorer retention with error counts rising to 16 ± 12.25 at one-week, 17.50 ± 23 at one-month and 41.45 ± 26 at 3-months, p<0.01. A similar effect was noted for the number of assistive prompts required, procedural time and hand path length. In the real-world assessment, both groups significantly improved their acetabular component positioning accuracy, and these improvements were equally maintained (p<0.01).

Daily VR training facilitates faster skills acquisition; however weekly practice has superior skills retention.

The purpose of the study was to compare the mechanical properties, oxidation and wear resistance of a vitamin E blended and moderately crosslinked polyethylene for total knee arthroplasty (MXE) in comparison with clinically established polyethylene materials.

The following polyethylene materials were tested: CPE (30 kGy e-beam sterilized), XLPE (75 kGy gamma crosslinked @ 100°C), ViXLPE (0.1 % vitamin E blended, 80 kGy e-beam crosslinked @ 100°C), and MXE (0.1 % vitamin E blended polyethylene, 30 kGy gamma sterilized). For the different tests, the polyethylene materials were either unaged or artificially aged for two or six weeks according to ASTM F2003-02.

The oxidation index was measured based on ASTM F2102 at a 1 mm depth. Small punch testing was performed based on ASTM F2977. Mechanical properties were measured on unaged materials according to ASTM D638.

Wear simulation was performed on a load controlled 3 + 1 station knee wear simulator (EndoLab GmbH, Thansau, Germany) capable of reproducing loads and movement of highly demanding activities (HDA) as well as ISO 14243-1 load profiles. The load profiles were applied for 5 million cycles (mc) or delamination of the polyethylene components. Medium size AS e.motion^® PS Pro (Aesculap AG, Tuttlingen, Germany) femoral and tibial components with a ZrN-multilayer surface, as well as Columbus^® CR cobalt-chrome alloy femoral and tibial components were tested. Particle analysis was performed on the serum samples of the ISO 14243-1 wear simulations based on ISO 17853:2011 and ASTM F1877.

The analysis of the mechanical properties show that moderately crosslinked polyethylene (MXE) might be a superior material for total knee arthroplasty applications [Schwiesau et al. 2021]. The addition of vitamin E in a moderately crosslinked polyethylene prevented its oxidation, kept its mechanical characteristics, and maintained a low wear, even under a HDA knee wear simulation.

The objectives of the study were to investigate demographic, injury and surgery/treatment-associated factors that could influence clinical outcome, following Autologous Chondrocyte Implantation (ACI) in a large, “real-world”, 20 year longitudinally collected clinical data set.

Multilevel modelling was conducted using R and 363 ACI procedures were suitable for model inclusion. All longitudinal post-operative Lysholm scores collected after ACI treatment and before a second procedure (such as knee arthroplasty but excluding minor procedures such as arthroscopy) were included. Any patients requiring a bone graft at the time of ACI were excluded. Potential predictors of ACI outcome explored were age at the time of ACI, gender, smoker status, pre-operative Lysholm score, time from surgery, defect location, number of defects, patch type, previous operations, undergoing parallel procedure(s) at the time of ACI, cell count prior to implantation and cell passage number.

The best fit model demonstrated that for every yearly increase in age at the time of surgery, Lysholm scores decreased by 0.2 at 1-year post-surgery. Additionally, for every point increase in pre-operative Lysholm score, post-operative Lysholm score at 1 year increased by 0.5. The number of cells implanted also impacted on Lysholm score at 1-year post-op with every point increase in log cell number resulting in a 5.3 lower score. In addition, those patients with a defect on the lateral femoral condyle (LFC), had on average Lysholm scores that were 6.3 points higher one year after surgery compared to medial femoral condyle (MFC) defects. Defect grade and location was shown to affect long term Lysholm scores, those with grade 3 and patella defects having on average higher scores compared to patients with grade 4 or trochlea defects.

Some of the predictors identified agree with previous reports, particularly that increased age, poorer pre-operative function and worse defect grades predicted poorer outcomes. Other findings were more novel, such as that a lower cell number implanted and that LFC defects were predicted to have higher Lysholm scores at 1 year and that patella lesions are associated with improved long-term outcomes cf. trochlea lesions.

Stem cell therapy is an effective means to address the repair of large segmental bone defects. However, the intense inflammatory response triggered by the implants severely impairs stem cell differentiation and tissue regeneration. High-dose transforming growth factor β1 (TGF-β1), the most locally expressed cytokine in implants, inhibits osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and promotes tissue fibrosis, severely compromising the efficacy of stem cell therapy. Small molecule inhibitors of TGF-β1 can be used to ameliorate the osteogenic disorders caused by high concentrations of TGF-β1, but systemic inhibition of TGF-β1 function will cause strong adverse effects. How to find safe and reliable molecular targets to antagonize TGF-β1 remains to be elucidated. Orphan nuclear receptor Nr4a1, an endogenous inhibitory molecule of TGF-β1, suppresses tissue fibrosis, but its role in BMSC osteogenesis is unclear. We found that TGF-β1 inhibited Nr4a1 expression through HDAC4. Overexpression of Nr4a1 in BMSCs reversed osteogenic differentiation inhibited by high levels of TGF- β1. Mechanistically, RNA sequencing showed that Nr4a1 activated the ECM-receptor interaction and Hippo signaling pathway, which in turn promoted BMSC osteogenesis. In bone defect repair and fracture healing models, transplantation of Nr4a1-overexpressing BMSCs into C57BL/6J mice or treatment with the Nr4a1 agonist Csn-B significantly ameliorated inflammation-induced bone regeneration disorders. In summary, our findings confirm the endogenous inhibitory effect of Nr4a1 on TGF- β1 and uncover the effectiveness of Nr4a1 agonists as a therapeutic tool to improve bone regeneration, which provides a new solution strategy for the treatment of clinical bone defects and inflammatory skeletal diseases.

Osteochondral injuries are a recognised factor in the development of osteoarthritis (OA). Mesenchymal stromal cells (MSCs) represent a promising biological therapeutic option as an OA-modifying treatment, and they also secrete factors that may have an anti-catabolic effect and/or encourage endogenous repair. We aim to study the effects of (i) intra-articular injection of human bone-marrow-derived MSCs and (ii) their secretome on recovery in a murine knee osteochondral injury model.

The MSC secretome was generated by stimulating human bone-marrow-derived MSCs with tumour necrosis factor alpha (TNFα). Mice (n=48) were injected with i) MSC secretome, ii) MSCs or iii) cell culture medium (control). Pain was assessed by activity monitoring, and cartilage repair, subchondral bone volume and synovial inflammation were evaluated using histology and microCT.

Both MSC- and MSC-secretome-injected mice showed significant pain reduction at day 7 when compared to control mice, but only the MSC-injected mice maintained a significant improvement over the controls at day 28. Cartilage repair was significantly improved in MSC-injected mice. No significant effects were observed with regards to synovial inflammation or subchondral bone volume.

The MSC secretome demonstrates regenerative effects but this does not appear to be as sustained as a MSC cell therapy. Further studies are required to investigate if this can be overcome using different dosing regiments for injection of the MSC secretome. As we further understand the regenerative properties of the MSC secretome, we may be able to enhance the clinical translatability of these therapies. Direct intra-articular injection of MSCs for the treatment of OA also appears promising as a potential future strategy for OA management.

Acknowledgements: MS is supported by a grant from the Wellcome Trust (PhD Programme for Clinicians)

Many age-related diseases affect our skeletal system, but bone health-targeting drug development strategies still largely rely on 2D in vitro screenings. We aimed at developing a scaffold-free progenitor cell-based 3D biomineralization model for more physiological high-throughput screenings.

MC3T3-E1 pre-osteoblast spheroids were cultured in V-shaped plates for 28 days in alpha-MEM (10% FCS, 1% L-Gln, 1X NEAA) with 1% pen/strep, changed every two days, and differentiation was induced by 10mM b-glycerophosphate and 50µg/ml ascorbic-acid. Osteogenic cell differentiation was assessed through profiling mRNA expression of selected osteogenic markers by efficiency corrected normalized 2^DDCq RT-qPCR. Biomineralization in spheroids was evaluated by histochemistry (Alizarin Red/von Kossa staining), Alkaline phosphatase (Alp) activity, Fourier transform infrared spectroscopy (FTIR) analyses, micro-CT analyses, and scanning electron microscopy on critical point-dried samples. GraphPad Prism 9 analyses comprised Shapiro-Wilk and Brown-Forsythe tests as well as 2-way ANOVA with Tukey post-hoc and non-parametric Kruskal-Wallis with Dunn post-hoc tests.

During mineralization, as opposed to non-mineralizing conditions, characteristic mRNA expression profiles of selected early and late osteoblast differentiation markers (e.g., RunX, Alp, Col1a1, Bglap) were observed between day 0 and 28 of culture; Alp was strongly upregulated (p<0.001) from day 7 on, followed by its enzymatic activity (p<0.001). Bglap and Col1a1 expression peaked on (p<0.001) and from day 14 on (p<0.05), respectively. IHC revealed osteocalcin staining in the spheroid core regions at day 14, while type I collagen staining of the cores was most prominent from day 21 on. Alizarin Red and Von Kossa confirmed central and radially outwards expanding mineralization patterns between day 14 and day 28, which was accompanied by a steady increase in extracellular calcium deposition over time (p<0.001). Micro-CT analyses allowed quantitative appreciation of the overall increase in mineral density over time (day21, p<0.05; d28, p<0.001), while SEM-EDX and FTIR ultimately confirmed a bone-like hydroxyapatite mineral deposition in 3D.

A novel and thoroughly characterized versatile bone-like 3D biomineralization in vitro model was established, which allows for studying effects of pharmacological interventions on bone mineralization ex vivo under physiomimetic conditions. Ongoing studies currently aim at elucidating in how far it specifically recapitulates intramembranous ossification.

Surgical debridement for medial epicondylitis (ME) is indicated for patients with refractory ME. The clinical efficacy of simple debridement has not been studied sufficiently. Moreover, authors experienced surgical outcome of ME was not as good as lateral epicondylitis. In this regard, authors have combined the atelocollagen injection in the debridement surgery of ME. The purpose of study was to compare clinical outcomes between simple debridement and debridement combined with atelocollagen injection in the ME.

Twenty-five patients with refractory ME and underwent surgical debridement were included in the study. Group A (n=13) was treated with isolated debridement surgery, and group B (n=12) was treated with debridement combined with 1.0 mL of type I atelocollagen. Pain and functional improvements were assessed using visual analogue scale, Mayo Elbow Performance Score (MEPS) and quick Disabilities of the Arm, Shoulder and Hand (DASH) scale respectively before surgery, at 3, 6 months after surgery and at the final follow-up.

Demographic data did not show significant difference between two groups before surgical procedures. Both groups showed improvement in pain and functional score postoperatively. However, at the 3 months after surgery, group B showed significantly better improvement as compared to group A(VAS 3.1 / 2.0, MEPS 71/82 qDASH 29/23). At the 6 months after surgery and final follow-up, both groups did not show any difference.

Surgical debridement combined with atelocollagen is effective treatment option in refractory ME and showed better short-term outcomes compared to isolated surgery.

Over the last decades, biodegradable metals emerged as promising materials for various biomedical implant applications, aiming to reduce the use of permanent metallic implants and, therefore, to avoid additional surgeries for implant removal. However, among the important issue to be solved is their fast corrosion - too high to match the healing rate of the bone tissue. The most effective way to improve this characteristic is to coat biodegradable metals with substituted calcium phosphates. Tricalcium phosphate (β-TCP) is a resorbable bioceramic widely used as synthetic bone graft. In order to modulate and enhance its biological performance, the substitution of Ca2+ by various metal ions, such as strontium (Sr2+), magnesium (Mg2+), iron (Fe2+) etc., can be carried out. Among them, copper (Cu2+), manganese (Mn2+), zinc (Zn2+) etc. could add antimicrobial properties against implant-related infections. Double substitutions of TCP containing couples of Cu2+/Sr2+ or Mn2+/Sr2+ ions are considered to be the most perspective based on the results of our study. We established that single phase Ca3−2x(MˊMˊˊ)x(PO4)2 solid solutions are formed only at x ≤ 0.286, where Mˊ and Mˊˊ—divalent metal ions, such as Zn2+, Mg2+, Cu2+, Mn2+, and that in case of double substitutions, the incorporation of Sr2+ ions allows one to extend the limit of solid solution due to the enlargement of the unit cell structure. We also reported that antimicrobial properties depend on the substitution ion occupation of Ca2+ crystal sites in the β-TCP structure. The combination of two different ions in the Ca5 position, on one side, and in the Ca1, Ca2, Ca3, and Ca4 positions, on another side, significantly boosts antimicrobial properties. In the present work, zinc-lithium (Zn-Li) biodegradable alloys were coated with double substituted Mn2+/Sr2+ β-TCP and double substituted Cu2+/ Sr2+ β-TCP, with the scope to promote osteoinductive effect (due to the Sr2+ presence) and to impart antimicrobial properties (thanks to Cu2+ or Mn2+ ions). The Pulsed Laser Deposition (PLD) method was applied as the coating's preparation technique. It was shown that films deposited using PLD present good adhesion strength and hardness and are characterized by a nanostructured background with random microparticles on the surface. For coatings characterization, Fourier Transform Infrared Spectroscopy, X-ray Diffraction, and Scanning Electron Microscopy coupled with Energy Dispersive X-ray and X-ray Photoelectron Spectroscopy were applied. The microbiology tests on the prepared coated Zn-Li alloys were performed with the Gram-positive (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative (Salmonella typhimurium, Escherichia coli) bacteria strains and Candida albicans fungus. The antimicrobial activity tests showed that Mn2+/Sr2+ β-TCP -coated and Cu2+/Sr2+ β-TCP coated Zn-Li alloys were able to inhibit the growth of all five microorganisms. The prepared coatings are promising in improving the degradation behavior and biological properties of Zn-Li alloys, and further studies are necessary before a possible clinical translation.

Decreasing the chance of local relapse or infection after surgical excision of bone metastases is a main goals in orthopedic oncology. Indeed, bone metastases have high incidence rate (up to 75%) and important cross-relations with infection and bone regeneration. Even in patients with advanced cancer, bone gaps resulting from tumor excision must be filled with bone substitutes. Functionalization of these substitutes with antitumor and antibacterial compounds could constitute a promising approach to overcome infection and tumor at one same time. Here, for the first time, we propose the use of nanostructured zinc-bone apatite coatings having antitumor and antimicrobial efficacy. The coatings are obtained by Ionized Jet Deposition from composite targets of zinc and bovine-derived bone apatite. Antibacterial and antibiofilm efficacy of the coatings is demonstrated in vitro against S. Aureus and E. Coli. Anti-tumor efficacy is investigated against MDA- MB-231 cells and biocompatibility is assessed on L929 and MSCs.

A microfluidic based approach is used to select the optimal concentration of zinc to be used to obtain antitumor efficacy and avoid cytotoxicity, exploiting a custom gradient generator microfluidic device, specifically designed for the experiments. Then, coatings capable of releasing the desired amount of active compounds are manufactured. Films morphology, composition and ion-release are studies by FEG- SEM/EDS, XRD and ICP. Efficacy and biocompatibility of the coatings are verified by investigating MDA, MSCs and L929 viability and morphology by Alamar Blue, Live/Dead Assay and FEG-SEM at different timepoints. Statistical analysis is performed by SPSS/PC + Statistics TM 25.0 software, one-way ANOVA and post-hoc Sheffe? test. Data are reported as Mean ± standard Deviation at a significance level of p <0.05.

Results and Discussion. Coatings have a nanostructured surface morphology and a composition mimicking the target. They permit sustained zinc release for over 14 days in medium. Thanks to these characteristics, they show high antibacterial ability (inhibition of bacteria viability and adhesion to substrate) against both the gram + and gram – strain.

The gradient generator microfluidic device permits a fine selection of the concentration of zinc to be used, with many potential perspectives for the design of biomaterials. For the first time, we show that zinc and zinc-based coatings have a selective efficacy against MDA cells. Upon mixing with bone apatite, the efficacy is maintained and cytotoxicity is avoided. For the first time, new antibacterial metal-based films are proposed for addressing bone metastases and infection at one same time. At the same time, a new approach is proposed for the design of the coatings, based on a microfluidic approach. We demonstrated the efficacy of Zn against the MDA-MB-231 cells, characterized for their ability to form bone metastases in vivo, and the possibility to use nanostructured metallic coatings against bone tumors. At the same time, we show that the gradient-generator approach is promising for the design of antitumor biomaterials. Efficacy of Zn films must be verified in vivo, but the dual-efficacy coatings appear promising for orthopedic applications.

Miniscrew implants (MSIs) are widely used to provide absolute anchorage for the orthodontic treatment. However, the application of MSIs is limited by the relatively high failure rate (22.86%). In this study, we wished to investigate the effects of amorphous and crystalline biomimetic calcium phosphate coating on the surfaces of MSIs with or without the incorporated BSA for the osteointegration process with an aim to facilitate the early loading of MSIs.

Amorphous and crystalline coatings were prepared on titanium mini-pin implants. Characterizations of coatings were examined by Scanning electron microscopy (SEM), Confocal laser-scanning dual-channel-fluorescence microscopy (CLSM) and Fourier-transform infrared spectroscopy (FTIR). The loading and release kinetics of bovine serum albumin (BSA) were evaluated by Enzyme linked immunosorbent assay (ELISA). Activity of alkaline phosphate (ALP) was measured by using the primary osteoblasts. In vivo, a model of metaphyseal tibial implantation in rats was used (n=6 rats per group). We had 6 different groups: no coating no BSA, no coating but with surface adsorption of BSA and incorporation of BSA in the biomimetic coating in the amorphous and crystalline coatings. Time points were 3 days, 1, 2 and 4 weeks. Histological and histomorphometric analysis were performed and the bone to implant contact (BIC) of each group was compared.

In vitro, the incorporation of BSA changed the crystalline coating from sharp plates into curly plates, and the crystalline coating showed slow-release profile. The incorporation of BSA in crystalline coating significantly decreased the activity of ALP in vitro. In vivo study, the earliest significant increase of BIC appeared in crystalline coating group at one week.

The crystalline coating can serve as a carrier and slow release system for the bioactive agent and accelerate osteoconductivity at early stage in vivo. The presence of BSA is not favorable for the early establishment of osteointegration.

Hip precautions are currently practiced in three-quarters of trauma hospitals in the UK, despite national recommendations from the ‘Blue Book’ not stating it as a requirement. Valuable therapist time is utilised alongside the need for specialised equipment, which can potentially delay discharge whilst it is being arranged. Objective of this study was to explore the current practice of the use of hip precautions on discharge following hemiarthroplasty for hip fractures. To also explore whether they are necessary and to identify areas for improvement to benefit patient care overall.

Online survey distributed to various Trauma and Orthopaedic Departments across the UK. Survey was available over a 4-month period, collecting 55 responses overall.

Majority of responses were from trauma and orthopaedic consultants who were aware of the ‘Blue Book’ recommendations. The majority of trusts who responded did not practice hip precautions and did not feel this increased the risk of dislocations on discharge. Recommendations included integration of hip precautions in the post-op advice in coordination with the physiotherapist and information leaflets on discharge regarding hip precautions. Hip precautions were not commonly practiced, for reasons including patient compliance and the inherently stable procedure of a hemiarthroplasty compared to a THR, reducing the need for hip precautions.

Hip precautions are not widely regarded as a useful practice for post-hip hemiarthroplasty, viewed as utilising more resources and increasing costs and risk due to increased hospital stay. Thus, this potentially delays discharge overall. A consistent approach should be implemented in treating patients post-hip hemiarthroplasty.

Bone healing outcome is highly dependent on the initial mechanical fracture environment [1]. In vivo, direct bone healing requires absolute stability and an interfragmentary strain (IFS) below 2% [2]. In the majority of cases, however, endochondral ossification is engaged where frequency and amplitude of IFS are key factors. Still, at the cellular level, the influence of those parameters remains unknown. Understanding the regulation of naïve hMSC differentiation is essential for developing effective bone healing strategies.

Human bone-marrow-derived MSC (KEK-ZH-NR: 2010–0444/0) were embedded in 8% gelatin methacryol. Samples (5mm Ø x 4mm) were subjected to 0, 10 and 30% compressive strain (5sec compression, 2hrs pause sequence for 14 days) using a multi-well uniaxial bioreactor (RISystem) and in presence of chondro-permissive medium (CP, DMEM HG, 1% NEAA, 10 µM ITS, 50 µg/mL ascorbic acid, and 100 mM Dex). Cell differentiation was assessed by qRT-PCR and histo-/immunohistology staining. Experiments were repeated 5 times with cells from 5 donors in duplicate. ANOVA with Tukey post-hoc correction or Kurskal-Wallis test with Dunn's correction was used.

Data showed a strong upregulation of hypertrophic related genes COMP, MMP13 and Type 10 collagen upon stimulation when compared to chondrogenic SOX9, ACAN, Type 2 collagen or to osteoblastic related genes Type 1 Collagen, Runx2. When compared to chondrogenic control medium, cells in CP with or without stimulation showed low proteoglycan synthesis as shown by Safranine-O-green staining. In addition, the cells were significantly larger in 10% and 30% strain compared to control medium with 0% strain. Type 1 and 10 collagens immunostaining showed stronger Coll 10 expression in the samples subjected to strain compared to control.

Uniaxial deformation seems to mainly promote hypertrophic-like chondrocyte differentiation of MSC. Osteogenic or potentially late hypertrophic related genes are also induced by strain.

Acknowledgments: Funded by the AO Foundation, StrainBot sponsored by RISystemAG & PERRENS 101 GmbH

Prosthetic Joint Infection (PJI) is a devastating complication that can occur after total joint replacement surgery. With increasing antimicrobial resistance, there is a need for non-antibiotic approaches to treat and prevent PJI. Doping calcium phosphates with antimicrobial ions shows promise for these purposes. This systematic review aims to search and summarise the evidence-base for the potential of calcium phosphates doped with different antimicrobial ions.

A systematic review was conducted on PubMed, Embase, Web-Of-Science, Cochrane Library and Emcare of in vitro and animal studies on the antimicrobial activity of (co)substituted calcium phosphates according to PRIMSA guidelines.. The research protocol, listing search terms and in/exclusion criteria, was registered a priori at https://doi.org/10.7910/DVN/HEP18U. Data was extracted regarding ions, micro-organisms and antimicrobial activity.

The search retrieved 1017 hits of which 148 papers were included. The substitution of 33 different ions was reported. Silver (n= 46), zinc (n=39), copper (n=18) and magnesium (n=14) were the most commonly doped ions. 36 different micro-organisms were studied of which E. coli (n=109), S. aureus (n=99), and C. albicans (n=22) were the most common. 6 different outcomes were reported, most commonly the K-ratio (n=53), the log CFU (n=41) and the bacterial inhibition zone (n=39). A validated outcome for the evaluation of biofilm prevention was lacking.

There was considerable heterogeneity in studied ions, micro-organisms and reported outcomes. A lack of clearly defined reporting guidelines in the field of antimicrobial materials has led to the use of clinically irrelevant micro-organisms and a general lack of consistency of the methods used and the reported results. Currently, there is no universally accepted measure for the effectiveness required from biomaterials for treatment and prevention of PJI.

Cartilage degeneration and loss are key events in the initiation and progression of osteoarthritis (OA). Changes to chondrocyte volume and morphology (in the form of cytoplasmic processes) and thus cell phenotype are implicated, as they lead to the production of a mechanically-weakened extracellular matrix. The chondrocyte cytoskeleton is intimately linked to cell volume and morphology and hence we have investigated alterations to levels and distribution of chondrocyte F-actin that occur during early OA.

The femoral heads (FH) from hip joints (N=16) were obtained with ethical permission and patient consent following femoral neck fracture. Cartilage was assessed as grade 0 (non-degenerate) and grade 1 (superficial fibrillation) using OARSI criteria. In situ chondrocyte volume and F-actin distribution were assessed using the fluorescent indicators (5-chloromethyl fluorescein diacetate (CMFDA)) and phalloidin, and imaged and quantified by confocal microscopy, Imaris^TM and ImageJ software.

There were no differences between the volume or total F-actin levels of in situ chondrocytes within the superficial zone of grade 0 (n=164 cells) compared to grade 1 (n=145) cartilage (P>0.05). However, a more detailed analysis of phalloidin labelling was performed, which demonstrated significant increases in both intense punctuate (IP) or intense areas (IA) (P<0.0001; P=0.0175 respectively). A preliminary analysis of IP and IA F-actin labelling suggested that while the former did not appear to be associated with changes to chondrocyte morphology, most of the cytoplasmic processes were associated with the presence of IA at the starting point of the protrusion.

These results demonstrate marked changes to F-actin distribution in chondrocytes in the very early stages of cartilage degeneration as occurs in OA. These subtle changes are probably an early indication of a change to the chondrocyte phenotype and thus worthy of further study as they may lead to deleterious alterations to matrix metabolism and ultimately cartilage weakening.

The Nottingham Hip Fracture Score (NHFS) was developed in 2007 as a predictor of 30-day mortality after hip fracture surgery following a neck of femur fracture. The National Hip Fracture Database is the standard used which calculated their own score using national data.

The NHF score for 30-day mortality was calculated for 50 patients presenting with a fractured neck femur injury between January 2020 to March 2020. A score <5 was classified as low risk and >/=5 as high risk. Aim was to assess the accuracy in calculating the Nottingham Hip Fracture Score against the National Hip Fracture Database. To explore whether it should it be routinely included during initial assessment to aid clinical management?

There was an increase in the number of mortalities observed in patients who belonged to the high-risk group (>=5) compared to the low risk group. COVID-19 positive patients had worse outcomes with average 30-day mortality of 6.78 compared to the average of 6.06. GEH NHF score per month showed significant accuracy against the NHFD scores.

The identification of high-risk groups from their NHF score can allow for targeted optimisations and elucidation of risk factors easily gathered at the point of hospitalisation. The NHFS is a valuable tool and useful predictor to stratify the risk of 30-day mortality and 1-year mortality after hip fracture surgery. Inclusion of the score should be considered as mandatory Trust policy for neck of femur fracture patients to aid clinical management and improve patient safety overall.

Proximal humeral shaft fractures are commonly treated with long straight plates or intramedullary nails. Helical plates might overcome the downsides of these techniques as they are able to avoid the radial nerve distally. The aim of this study was to investigate in an artificial bone model: (1) the biomechanical competence of different plate designs and (2) to compare them against the alternative treatment option of intramedullary nails.

Twenty-four artificial humeri were assigned in 4 groups and instrumented as follows: group1 (straight 10-hole-PHILOS), group2 (MULTILOCK-nail), group3 (45°-helical-PHILOS) and group4 (90°-helical-PHILOS). An unstable proximal humeral shaft fracture was simulated. Specimens were tested under quasi-static loading in axial compression, internal/external rotation and bending in 4 directions monitored by optical motion tracking.

Axial displacement (mm) was significantly lower in group2 (0.1±0.1) compared to all other groups (1: 3.7±0.6; 3: 3.8±0.8; 4: 3.5±0.4), p<0.001. Varus stiffness in group2 (0.8±0.1) was significantly higher compared to groups1+3, p≤0.013 (1: 0.7±0.1; 3: 0.7±0.1; 4: 0.8±0.1). Varus bending (°) was significantly lower in group2 compared to all other groups (p<0.001) and group4 to group1, p=0.022. Flexion stiffness in group1 was significantly higher compared to groups2+4 (p≤0,03) and group4 to group1, p≤0,029 (1: 0.8±0.1; 2: 0.7±0.1; 3: 0.7±0.1; 4: 0.6±0.1). Flexion bending (°) in group4 was higher compared to all other groups (p≤0.024) and lower in group2 compared to groups1+4, p≤0.024. Torsional stiffness remained non significantly different, p≥0.086. Torsional deformation in group2 was significantly higher compared to all other groups, p≤0.017. Shear displacement remained non significantly different, p≥0.112.

From a biomechanical perspective, helical plating with 45° and 90° may be considered as a valid alternative fixation technique to standard straight plating of proximal third humeral fractures. Intramedullary nails demonstrated higher axial and bending stiffness as well as lower fracture gap movements during axial loading compared to all plate designs. However, despite similar torsional stiffness they were associated with higher torsional movements during internal/external rotation as compared to all investigated plate designs.

Despite the major advances in osteosynthesis after trauma, there remains a small proportion of patients (<10%) who exhibit delayed healing and/or eventual progression to non-union. While known risk factors exist, e.g. advanced age or diabetes, the exact molecular mechanism underlying the impaired healing is largely unknown and identifying which specific patient will develop healing complications is still not possible in clinical practice. The talk will cover our novel multimodal approaches in small animals, which have the potential to precisely capture and understand biological changes during fracture healing on an individual basis. Via combining emerging omics technologies with our recently developed femur defect loading equipment in mice, we provide a platform to precisely link mechanical and molecular analyses during fracture healing.

Solid organ transplant (SOT) recipients present an increased medical risk; however, few studies analyze the outcomes of these patients undergoing hip fracture surgery. This study aimes to determine the incidence of hip fracture in SOT patients and to compare the outcomes of SOT patients with matched non-SOT controls after hip fracture fixation.

A retrospective review identified 20 SOT patients with hip fracture at a single center from 2016 to 2021 and were matched (1:1) with a cohort of 20 patients with hip fracture without SOT. Patient outcomes, mortality/survival and clinical outcomes were compared between two groups.

The incidence of hip fracture in SOT patients was 20/1787, 1.1%. There were significant differences in mortality rate (73.3% SOT group vs. 26.7% non-SOT group; p<0.05). There were no differences in survival time (p=0.746). There were no differences in time to surgery (5.0 days SOT group vs. 3.1 days non-SOT group; p=0.109), however, there were significant differences in the hospital length of stay (14 days SOT group vs. 8.6 days non-SOT group; p=0.018). There were no differences regarding the complication rate between the two groups (9/20, 45% vs. 6/20, 30% in the SOT and non-SOT groups, respectively).

SOT patients with associated hip fracture required longer hospital length of stay than non-SOT patients. SOT patients did not show greater clinical complications; however, they presented higher mortality rate compared to non-SOT patients.

Bone regeneration is an area of acute medical need, but its clinical success is hampered by the need to ensure rapid vascularization of osteogenic grafts. Vascular Endothelial Growth Factor (VEGF) is the master regulator of vascular growth and during bone development angiogenesis and osteogenesis are physiologically coupled through so-called angiocrine factors produced by blood vessels. However, how to exploit this process for therapeutic bone regeneration remains a challenge (1).

Here we will describe recent work aiming at understanding the cross-talk between vascular growth and osteogenesis under conditions relevant for therapeutic bone regeneration. To this end we take advantage of a unique platform to generate controlled signalling microenvironments, by the covalent decoration of fibrin matrices with tunable doses and combinations of engineered growth factors. The combination of human osteoprogenitors and hydroxyapatite in these engineered fibrin matrices provides a controlled model to investigate how specific molecular signals regulate vascular invasion and bone formation in vivo. In particular, we found that:

In conclusion, vascularization of osteogenic grafts is not simply necessary in order to enable progenitor survival. Rather, blood vessels can actively stimulate bone regeneration in engineered grafts through specific molecular signals that can be harnessed for therapeutic purposes.

Acknowledgements: This work was supported in part by the European Union Horizon 2020 Program (Grant agreement 874790 – cmRNAbone).

For any figures and tables, please contact the authors directly.

COVID-19 was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The initial response to the pandemic included the cessation of routine services including elective orthopaedic surgery. There was apprehension among both surgeons and patients about restarting elective surgical services. The high mortality rate in perioperative patients who contract COVID-19 was of particular concern. The aim of this study was to identify the perioperative viral transmission rate in orthopaedic patients at our institution following the restart of elective surgery between August 2020 and November 2020 after the first wave of Covid in the UK.

All patients who had their elective Orthopaedic surgeries at our institution from 1st August 2020 to 30th November 2020 were checked whether they were Covid positive or experienced COVID symptoms within 2 weeks after the operation. All patients were advised a 14-day period of comprehensive social distancing, 3 days of self-isolation and had a negative COVID-19 test within 72 hours of surgery and underwent surgery at a COVID free site. The patients were contacted and the hospital database was searched to identify those patients who were Covid positive or had Covid symptoms after the surgery. Baseline patient characteristics were recorded including age, gender, procedure, the subspeciality and admission type. Patients who underwent emergency procedures and trauma operations were excluded.

Out of the 499 patients, 315 were contacted over telephone and hospital database was searched for the rest of the patients. We found that none of the patients were positive for COVID or had symptoms of COVID within two weeks of surgery. 5 patients were COVID positive with symptoms few months after the procedure and all of them recovered. There were 144 inpatient admissions and 353 day cases.

The development of a COVID-free pathway for elective orthopaedic patients results in very low viral transmission rates. Findings of our study confirms that COVID-free elective pathway is an efficient process, and this could be implemented in future elective Orthopaedic surgeries during COVID times. Elective surgery can be safely resumed using dedicated pathways and procedures -Surgeons, hospital staff and patients should remain vigilant.

In the last decades, the use of artificial intelligence (AI) has been increasingly investigated in intervertebral disc degeneration (IDD) and chronic low back pain (LBP) research. To date, several AI-based cutting-edge technologies, such as computer vision, computer-assisted diagnosis, decision support system and natural language processing have been utilized to optimize LBP prevention, diagnosis, and treatment. This talk will provide an outline on contemporary AI applications to IDD and LBP research, with a particular attention towards actual knowledge gaps and promising innovative tools.

Cartilage lesions often undergo irreversible progression due to low self-repair capability of this tissue. Tissue engineered approaches based in extrusion bioprinting of constructs loaded with stem cell spheroids may offer valuable alternatives for the treatment of cartilage lesions. Human mesenchymal stromal cell (hMSC) spheroids can be chondrogenically differentiated faster and more efficiently than single cells. This approach allows obtaining larger tissues in a rapid, controlled and reproducible way. However, it is challenging to control tissue architecture, construct stability, and cell viability during maturation. In this study we aimed at the development of a reproducible bioprinting process followed by post-bioprinting chondrogenic differentiation procedure using large quantities of hMSC spheroids encapsulated in a xanthan gum-alginate hydrogel. Multi-layered constructs were bioprinted, ionically crosslinked, and chondrogenically differentiated for 28 days. The expression of glycosaminoglycan, collagen II and IV were observed. After 56 days in culture, the bioprinted constructs were still stable and show satisfactory cell metabolic activity with profuse extracellular matrix production. These results showed a promising procedure to obtain 3D cartilage-like constructs that could be potential use as stable chondral tissue implants for future therapies.

Acknowledgments: The National Council for Scientific and Technological Development (CNPq, Brazil – Grants # 314 724/2021-4, 307 829/2018-9, 430 860/2018-8, 142 050/2018-0 and 465 656/2014-5), the Coordination for the Improvement of Higher Educational Personnel (CAPES, Brazil – PrInt 88 887.364849/2019-00 and PrInt 88 887.310405/2018-00), the Fund for Support to Teaching, Research and Extension from the University of Campinas (FAEPEX/UNICAMP, Brazil – Grants # 2921/18, 2324/21), and the European Union's Horizon 2020 JointPromise project – Precision manufacturing of microengineered complex joint implants, under grant agreement 874 837 are acknowledged for the financial support of this study.