Aseptic inflammation is the main factor causing aseptic loosening of artificial joints. Studies have shown that inflammatory cells can activate STING (stimulator of interferon genes, STING) after being stressed. This study aims to explore the specific mechanism of STING in aseptic loosening of artificial joints, and provide new strategies for disease prevention.

Titanium particles with a diameter of 1.2-10 μm were prepared to stimulate macrophages (RAW 264.7) to simulate the periprosthetic microenvironment. A lentiviral vector targeting the STING gene was designed and transfected into macrophages to construct a cell line targeting STING knockdown. The expression and secretion levels of TNF-α were detected by qPCR and ELISA, the activation levels of inflammatory pathways (NF-κB, IRF3, etc.) were detected by western blot, and the nucleus translocation of P65 and IRF3 was observed by cellular immunofluorescence.

After titanium particles stimulated macrophages, qPCR and ELISA showed that the transcription and secretion levels of TNF-α were significantly increased. Western blot showed that titanium particle stimulation could increase the phosphorylation levels of NF-κB and IRF3 pathways. While knockdown of STING can significantly reduce titanium particle-induced TNF production, attenuate the activation levels of NF-κB and IRF3 pathways as well as the nucleus translocation of P65 and IRF3.

Conclusions: STING positively regulates the level of inflammation in macrophages induced by titanium particles, and targeted inhibition of STING can reduce inflammation, which may delay the progression of aseptic loosening of artificial joints.

Osteoarthritis is a common articular cartilage disorder and causes a significant global disease burden. Articular cartilage has a limited capacity of repair and there is increasing interest in the use of cell-based therapies to facilitate repair including the use of Mesenchymal Stromal Cells (MSCs). There is some evidence in the literature that suggests that advancing age is associated with declining MSC function, including reduced proliferation and differentiation potential, and greater cellular apoptosis. In our study, we first performed a systematic review of the literature to determine the effects of chronological age on the in vitro properties of MSCs, and then performed a laboratory study to investigate these properties.

We initially conducted a PRISMA systematic review of the literature to review the evidence base for the effects of chronological age on the in vitro properties of MSCs including cell numbers, expansion, cell surface characterization and differentiation potential. This was followed by laboratory based experiments to assess these properties. Tissue from patients undergoing total knee replacement surgery was used to isolate MSCs from the bone fragments using a method developed in our laboratory. The growth kinetics was determined by calculating the population doublings per day. Following expansion in culture, MSCs at P2 were characterised for a panel of cell surface markers using flow cytometry. The cells were positive for CD73, CD90 and CD105, and negative for CD34 and CD45. The differentiation potential of the MSCs was assessed through tri-lineage differentiation assays. Clear differences between the younger and older patients were indicated.

Chronological age-related changes in MSC function have important implications on the use of these cells in clinical applications for an ageing population. The results from this study will be used to plan further work looking at the effects of chronological age on cellular senescence and identify pathways that could be targeted to potentially reverse any age-related changes.

Successful application of patient derived cells to engineer vascularized bone grafts is often hampered by low cell numbers and lengthy in vitro expansion. With sound induced morphogenesis (SIM), local cell density enhancement was shown to improve microvasculature formation at lower cell concentration than conventional methods [1]. SIM takes advantage of hydrodynamic forces that act on cells to arrange them within a hydrogel. Following, we are evaluating the potential of cell-hydrogel biografts with high local cell density to improve the therapeutic efficacy in clinical scenarios such as anastomosis or bone formation within non-union fractures.

To assess anastomosis, human umbilical vein endothelial cells (HUVEC) and human mesenchymal stromal cells (MSC) were mixed at a 1:1 ratio in PEG-based or Dextran-based hydrogels at a final concentration of 2×10⁶ cells×mL^-1. For ectopic bone formation, MSC were resuspended in PEG-based hydrogels at 2×10⁶ or 5×10⁶ cells×mL^-1, with or without BMP-2. Cells were assembled into distinct patterns at a frequency of 60 Hz. Four biografts of 4 × 9 mm² were implanted at the back of nude mice (total of 7 animals) and harvested after 2 or 8 weeks. Explants were fixed and imaged as whole constructs or embedded in paraffin for histological analysis.

Upon explantation, microscopic evaluation indicated that HUVEC were retained within the PEG-hydrogel after 2 weeks and formed a pre-vascular network. In the second study, ectopic bone formation was more pronounced in areas of higher local cell density based on visual inspection. Ongoing experiments are further characterizing bone formation by micro-CT and histological evaluation.

Our results indicate that local cell density enhancement by sound requires a lower initial cell concentration than conventional, static seeding methods to achieve comparable microvasculature structures or local osteogenesis.

Currently, fibrin glue obtained from fibrinogen and thrombin of human and animal blood are widely investigated to use as injectable hydrogel for tissue engineering which contributes to minimally invasive surgery, superior biodegradability, cell attachment, proliferation and regenerating new tissue. However, most of them fail to achieve to be used for tissue engineering application because of a risk of immune response and poor mechanical properties. To overcome the limitation of fibrin glue and to reduce the usage of products from human and animal blood, the artificial fibrin glue materials were developed. Recently, cellulose nanofiber (CNF) as reinforcing agent has been explored for many tissue engineering applications such as bone and cartilage due to its impressive biological compatibility, biodegradability and mechanical properties. CNF was extracted from cassava pulp. PEO-PPO-PEO diacrylate block copolymer is a biodegradable synthetic polymers which is water insoluble hydrogel after curing by UV light at low intensity. To enhance the cell adhesion abilities, gelatin methacrylate (GelMA), the denature form of collagen was used to incorporate into hydrogel. The aim of this study was to develop the artificial fibrin glue from CNF reinforced PEO-PPO-PEO diacrylate block copolymer/GelMA injectable hydrogel.

CNF/PEO-PPO-PEO diacrylate block copolymer/GelMA injectable hydrogels were prepared with 2-hydroxy-1-(4-(hydroxy ethoxy) phenyl)-2-methyl-1-propanone (Irgacure 2959) as a photoinitiator. The physicochemical properties were investigated by measuring various properties such as thickness, gel fraction, mechanical properties and water uptake.

At optimal preparation condition, CNF reinforced injectable hydrogel was successful prepared after curing with UV light within 7 minutes. This hydrogel showed gel fraction and water uptake of 81 and 85%, respectively. The cytotoxicity, cell adhesion and proliferation of CNF reinforced injectable hydrogel was presented.

Cellulose nanofiber from casava pulp was successfully used to prepare injectable hydrogel as artificial fibrin glue for tissue engineering. The hydrogel showed good physical properties which can be applied to use for tissue engineering application.

Intervertebral disc degeneration (IDD), the main cause of low back pain, is closely related to the inflammatory microenvironment in the nucleus pulposus (NP). Tumor necrosis factor-α (TNF-α) plays an important role in inflammation-related metabolic disturbance of NP cells. Melatonin has been proven to regulate the metabolism of NP cells, but whether it can protect NP cells from TNF-α-induced damage is still unclear. Therefore, this study aims to investigate the role and specific mechanism of melatonin on regulating the metabolism of NP cells in the inflammatory microenvironment.

Human primary NP cells were treated with or without vehicle, TNF-α and melatonin. And the metabolic markers were also detected by western blotting and RT-qPCR. The activity of NF-κB signaling and Hippo/YAP signaling were assessed by western blotting and immunofluorescence. Membrane receptors inhibitors, pathway inhibitors, lentiviral infection, plasmids transfection and immunoprecipitation were used to explore the specific mechanism of melatonin. In vivo, the rat IDD model were constructed and melatonin was injected intraperitoneally to evaluate its therapeutical effect on IDD.

We demonstrated that melatonin could alleviate the development of IDD in a rat model and reverse TNF-α–impaired metabolism of NP cells in vitro. Further investigation revealed that the protective effects of melatonin on NP cells mainly rely on MTNR1B, which subsequently activates Gαi2 protein. The activation of Gαi2 could upregulate the yes-associated protein (YAP) level, resulting in anabolic enhancement of NP cells. In addition, melatonin-mediated YAP upregulation increased the expression of IκBα and suppressed the TNF-α–induced activation of the NF-κB pathway, thereby inhibiting the catabolism of NP cells.

Our results revealed that melatonin can reverse TNF-α–impaired metabolism of NP cells via the MTNR1B/Gαi2/YAP axis and suggested that melatonin can be used as a potential therapeutic drug in the treatment of IDD.

Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor to maintain cellular redox homeostasis, but is also affecting bone metabolism. As the association between Nrf2 and osteoporosis in elderly females is not fully elucidated, our aim was to shed light on the potential contribution of Nrf2 to the development of age-dependent osteoporosis using a mouse model.

Female wild-type (WT, n=18) and Nrf2-knockout (KO, n=12) mice were sacrificed at different ages (12 weeks=young mature adult, and 90 weeks=old), morphological cortical and trabecular properties of femoral bone analyzed by micro-computed tomography (µCT), and compared to histochemistry. Mechanical properties were derived from quasi-static compression tests and digital image correlation (DIC) used to analyze full-field strain distribution. Bone resorbing cells and aromatase expression by osteocytes were evaluated immunohistochemically and empty osteocyte lacunae counted in cortical bone. Wilcoxon rank sum test was used for data comparison and differences considered statistically significant at p<0.05.

When compared to old WT mice, old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness (Ct.Th), cortical area (Ct.Ar), and cortical bone fraction (Ct.Ar/Tt.Ar). Surprisingly, these parameters were not different in skeletally mature young adult mice. Metaphyseal trabeculae were thin but present in all old WT mice, while no trabecular bone was detectable in 60% of old KO mice. Occurrence of empty osteocyte lacunae did not differ between both groups, but a significantly higher number of osteoclast-like cells and fewer aromatase-positive osteocytes were found in old KO mice. Furthermore, female Nrf2-KO mice showed an age-dependently reduced fracture resilience when compared to age-matched WT mice.

Our results confirmed lower bone quantity and quality as well as an increased number of bone resorbing cells in old female Nrf2-KO mice. Additionally, aromatase expression in osteocytes of old Nrf2-KO mice was compromised, which may indicate a chronic lack of estrogen in bones of old Nrf2-deficient mice. Thus, chronic Nrf2 loss seems to contribute to age-dependent progression of female osteoporosis.

Dual mobility hip arthroplasty utilizes a freely rotating polyethylene liner to protect against dislocation. As liner motion has not been confirmed in vivo, we investigated the liner kinematics in vivo using dynamic radiostereometry.

16 patients with Anatomical Dual Mobility acetabular components were included. Markers were implanted in the liners using a drill guide. Static RSA recordings and patient reported outcome measures were obtained at post-op and 1-year follow-up. Dynamic RSA recordings were obtained at 1-year follow-up during a passive hip movement: abduction/external rotation, adduction/internal rotation (modified FABER-FADIR), to end-range and at 45° hip flexion. Liner- and neck movements were described as anteversion, inclination and rotation.

Liner movement during modified FABER-FADIR was detected in 12 of 16 patients. Median (range) absolute liner movements were: anteversion 10° (5–20), inclination 6° (2–12), and rotation 11° (5–48) relative to the cup. Median absolute changes in the resulting liner/neck angle (small articulation) was 28° (12–46) and liner/cup angle (larger articulation) was 6° (4–21). Static RSA showed changes in median (range) liner anteversion from 7° (-12–23) postoperatively to 10° (-3–16) at 1-year follow-up and inclination from 42 (35–66) postoperatively to 59 (46–80) at 1-year follow-up. Liner/neck contact was associated with high initial liner anteversion (p=0.01).

The polyethylene liner moves over time. One year after surgery the liner can move with or without liner/neck contact. The majority of movement is in the smaller articulation between head and liner.

The aim of this research was to determine biomechanical markers which differentiate medial knee osteoarthritis (OA) patients who do and do not show structural progression over a 2-year period.

A cohort of 36 subjects was selected from a longitudinal study (Meireles et al 2017) using Kellgren-Lawrence (KL) scores at baseline and 2-year follow-up. The cohort consisted of 10 healthy controls (HC) (KL=0 at both time points), 15 medial knee OA non-progressors (NPKOA) (KL≥1 at baseline and no change over 2 years), and 11 medial knee OA progressors (PKOA) (KL≥1 at baseline and increase of ≥1 over 2 years). 3D integrated motion capture data from three walking trials were processed through a musculoskeletal modelling framework (Smith et al 2016) to estimate knee joint loading parameters (i.e., magnitude of mean contact pressure, and centre of pressure (COP)). Parameters at first and second peak were extracted and compared between groups using Kruskal-Wallis and Mann-Whitney tests.

Higher magnitudes were observed in PKOA vs NPKOA, and PKOA vs HC groups at both time points. Additionally, a posterior (1st and 2nd peak), and lateral (2nd peak) shift in medial compartment COP was shown between PKOA and NPKOA, and PKOA and HC subjects. Interestingly, in the studied parameters, no differences were observed between NPKOA and HC groups.

Significantly higher magnitude, and a more posterior and lateral COP was observed between PKOA and NPKOA patients. These differences, combined with an absence of difference between NPKOA and HC suggest structural OA progression is driven by a combination of altered loading magnitude and location. These results may serve as guidelines for targeted gait retraining rehabilitation to slow or stop knee OA progression whereby shifting COP anterior and medial and reducing magnitude by ~22% may shift patients from a PKOA to a NPKOA trajectory.

Osteoarthritis (OA) is a degenerative joint disease affecting millions worldwide. Early detection of OA and monitoring its progression is essential for effective treatment and for preventing irreversible damage. Although sensors have emerged as a promising tool for monitoring analytes in patients, their application for monitoring the state of pathology is currently restricted to specific fields (such as diabetes). In this study, we present the development of an optical sensor system for real-time monitoring of inflammation based on the measurement of nitric oxide (NO), a molecule highly produced in tissues during inflammation.

Single-walled carbon nanotubes (SWCNT) were functionalized with a single-stranded DNA (ssDNA) wrapping designed using an artificial intelligence approach and tested using S-nitroso-N-acetyl penicillamine (SNAP) as a standard released-NO marker. An optical SWIR reader with LED excitation at 650 nm, 730 nm and detecting emission above 1000 nm was developed to read the fluorescence signal from the SWCNTs. Finally, the SWCNT was embedded in GelMa to prove the feasibility of monitoring the release of NO in bovine chondrocyte and osteochondral inflamed cultures (1–10 ng/ml IL1β) monitored over 48 hours. The stability of the inflammation model and NO release was indirectly validated using the Griess and DAF-FM methods. A microfabricated sensor tag was developed to explore the possibility of using ssDNA-SWCNT in an ex vivo anatomic set-up for surgical feasibility, the limit of detection, and the stability under dynamic flexion.

The SWCNT sensor was sensitive to NO in both in silico and in vitro conditions during the inflammatory response from chondrocyte and osteochondral plug cultures. The fluorescence signal decreased in the inflamed group compared to control, indicating increased NO concentration. The micro-tag was suitable and stable in joints showing a readable signal at a depth of up to 6 mm under the skin.

The ssDNA-SWCNT technology showed the possibility of monitoring inflammation continuously in an in vitro set-up and good stability inside the joint. However, further studies in vivo are needed to prove the possibility of monitoring disease progression and treatment efficacy in vivo.

Acknowledgments: The project was co-financed by Innosuisse (grant nr. 56034.1 IP-LS)

Tendon diseases are prevalent health concerns for which current therapies present limited success, in part due to the intrinsically low regenerative ability of tendons. Therefore, tissue engineering presents a potential to improve this outcome. Here, we hypothesize that a concurrent control over both biophysical and biochemical stimuli will boost the tenogenic commitment of stem cells, thus promoting regeneration. To achieve this, we combine molecularly imprinted nanoparticles (MINPs), which act as artificial amplifiers for endogenous growth factor (GF) activity, with bioinspired anisotropic hydrogels² to manufacture 3D tenogenic constructs. MINPs were solid phase-imprinted using a TGF-β3 epitope as template and their affinity for the target was assessed by SPR and dot blot. Magnetically-responsive microfibers were produced by cryosectioning electrospun meshes containing iron oxide nanoparticles. The constructs were prepared by encapsulating adipose tissue-derived stem cells (ASCs), microfibers, and MINPs within gelatin hydrogels, while aligning the microfibers with an external magnetostatic field during gelation. This allows an effective modulation of hydrogel fibrillar topography, mimicking the native tissue's anisotropic architecture. Cell responses were analyzed by multiplex immunoassay, quantitative polymerase chain reaction, and immunocytochemistry. MINPs showed an affinity for the template comparable to monoclonal antibodies. Encapsulated ASCs acquired an elongated shape and predominant orientation along the alignment direction. Cellular studies revealed that combining MINPs with aligned microfibers increased TGF-β signaling via non-canonical Akt/ERK pathways and upregulated tendon-associated gene expression, contrasting with randomly oriented gels. Immunostaining of tendon-related proteins presented analogous outcomes, corroborating our hypothesis.

Our results thus demonstrate that microstructural cues and biological signals synergistically direct stem cell fate commitment, suggesting that this strategy holds potential for improving tendon healing and might be adaptable for other biological tissues. The proposed concept highlights the GF-sequestering ability of MINPs which allows a cost-effective alternative to recombinant GF supplementation, potentially decreasing the translational costs of tissue engineering strategies.

Acknowledgements: The authors acknowledge the funding from the European Union's Horizon 2020 under grant No. 772817; from FCT/MCTES for scholarships PD/BD/143039/2018 & COVID/BD/153025/2022 (S.P.B.T.), and PD/BD/129403/2017 (S.M.B.), co-financed by POCH and NORTE 2020, under the Portugal 2020 partnership agreement through the European Social Fund, for contract 2020.03410.CEECIND (R.M.A.D.) and project 2022.05526.PTDC; and from Xunta de Galicia for grant ED481B2019/025 (A.P.).

Successful anterior cruciate ligament (ACL) reconstructions strive a firm ligament-bone integration. Therefore, the aim of this study was to address in more detail the enthesis as the thriphasic bone attachment of the ACL using a tissue engineering approach. To establish a tissue-engineered enthesis-like construct, triphasic scaffolds embroidered from poly(L-lactide-co-caprolactone) and polylactic acid functionalized with collagen foam were colonized with osteogenically differentiated human mesenchymal stromal cells (hMSCs) and lapine (L) ACL fibroblasts.

These triphasic scaffolds with a bone-, a fibrocartilage transition- and a ligament phase were seeded directly after spheroid assembly or with 14 days precultured LACL fibroblast spheroids and 14 days osteogenically differentiated hMSCs spheroids (=longer preculture) and cultured for further 14 days. Cell survival was tested. Collagen type I and vimentin were immunolabeled and the content of DNA and sulfated glycosaminoglycan (sGAG) was quantified. The relative gene expression of tenascin C, type I and X collagens, Mohawk and Runx2 was analyzed.

Compared to the LACL spheroids the hMSC spheroids adhered better to the scaffold surface with faster cell outgrowth on the fibers. Collagen type I and vimentin were mainly detected in the hMSCs colonizing the bone zone. The DNA content was generally higher in the bone (hMSCs) than in the ligament zones and after short spheroid preculture higher than after longer preculture whereas the sGAG content was greater after longer preculture for both cell types. The longer precultivated hMSCs expressed more type I collagen in comparison to those only shortly precultured before scaffold seeding. Type I collagen and tenascin C were higher expressed in scaffolds directly colonized with LACL compared to those seeded after longer spheroid preculture. The gene expression of ECM components and transcription factors depended on cell type and preculturing condition.

Zonal colonization of triphasic scaffolds using the spheroid method is possible offering a novel approach for enthesis tissue engineering.

Lesions in the joint surface are commonly treated with osteoarticular autograft transfer system (OATS), autologous cell implantation (ACI/MACI), or microfracture. Tissue formed buy the latter commonly results in mechanically inferior fibrocartilage that fails to integrate with the surrounding native cartilage, rather than durable hyaline cartilage. Fractional laser treatment to make sub-millimeter (<500 µm) channels has been employed for tissue regeneration in the skin to facilitate rejuvenation without typical scarring. Additionally, we have pioneered a means to generate articular cartilage matrix from chondrocytes—dynamic Self-Regenerating Cartilage (dSRC). Combining these two approaches by performing fractional laser treatment of the joint cartilage and treating with dSRC is a new paradigm for joint surface restoration. This approach was refined in a series of in vitro experiments and tested in swine knee defects during a 6-month study in 12 swine.

dSRC are generated by placing 10⁷ swine knee chondrocytes into sealed 15-mL polypropylene tubes and cultured on a rocker at 40 cycles per minute for 14 days at 37°C. The chondrocytes aggregate and generate new extracellular matrix to form a pellet of dSRC. Channels of approximately 300-500 µm diameter were created by infrared laser ablation in swine cartilage (in vitro) and swine knees (in vivo). The diameter and depth of the ablated channel in the cartilage was controlled by the light delivery parameters (power, spot size, pulse duration) from a fractional 2.94 µm Erbium laser. The specimens were evaluated with histology (H&E, safranin O, toluidine blue) and polarized-sensitive optical coherence tomography for collagen orientation.

We can consistently create laser-ablated channels in the swine knee and successfully implant new cartilage from dSRC to generate typical hyaline cartilage in terms of morphology and biochemical properties. The neocartilage integrates with host cartilage in vivo.

These findings demonstrate our novel combinatorial approach for articular cartilage rejuvenation.

Implant removal after clavicle plating is common. Low-profile dual mini-fragment plate constructs are considered safe for fixation of diaphyseal clavicle fractures. The aim of this study was to investigate: (1) the biomechanical competence of different dual plate designs from stiffness and cycles to failure, and (2) to compare them against 3.5mm single superoanterior plating.

Twelve artificial clavicles were assigned to 2 groups and instrumented with titanium matrix mandible plates as follows: group 1 (G1) (2.5mm anterior+2.0mm superior) and group 2 (G2) (2.0mm anterior+2.0mm superior). An unstable clavicle shaft fracture (AO/OTA15.2C) was simulated. Specimens were cyclically tested to failure under craniocaudal cantilever bending, superimposed with torsion around the shaft axis and compared to previous published data of 6 locked superoanterior plates tested under the same conditions (G3).

Displacement (mm) after 5000 cycles was highest in G3 (10.7±0.8) followed by G2 (8.5±1.0) and G1 (7.5±1.0), respectively. Both outcomes were significantly higher in G3 as compared to both G1 and G2 (p≤0.027). Cycles to failure were highest in G3 (19536±3586) followed by G1 (15834±3492) and G2 (11104±3177), being significantly higher in G3 compared to G2 (p=0.004). Failure was breakage of one or two plates at the level of the osteotomy in all specimens. One G1 specimen demonstrated failure of the anterior plate. Both plates in other G1 specimens. Majority of G2 had fractures in both plates. No screw pullout or additional clavicle fractures were observed among specimens.

Low-profile 2.0/2.0 dual plates demonstrated similar initial stiffness compared to 3.5mm single plates, however, had significantly lower failure endurance. Low-profile 2.5/2.0 dual plates showed significant higher initial stiffness and similar resistance to failure compared to 3.5mm single locked plates and can be considered as a useful alternative for diaphyseal clavicle fracture fixation. These results complement the promising results of several clinical studies.

An increasing elderly population means joint replacement surgery numbers are projected to increase, with associated complications such as periprosthetic joint infections (PJI) also rising. PJI are particularly challenging due to antimicrobial resistant biofilm development on implant surfaces and surrounding tissues, with treatment typically involving invasive surgeries and systemic antibiotic delivery. Consequently, functionalisation of implant surfaces to prevent biofilm formation is a major research focus. This study characterises clinically relevant antimicrobials including gentamicin, clindamycin, daptomycin, vancomycin and caspofungin within a silica-based, biodegradable sol-gel coating for prosthetic devices.

Antimicrobial activity of the coatings against clinically relevant microorganisms was assessed via disc diffusion assays, broth microdilution culture methods and the MBEC assay used to determine anti-biofilm activity. Human and bovine cells were cultured in presence of antimicrobial sol-gel to determine cytotoxicity using Alamar blue and antibiotic release was measured by LC-MS. Biodegradability in physiological conditions was assayed by FT-IR, ICP-MS and measuring mass change. Effect of degradation products on osteogenesis were studied by culturing mesenchymal stem cells in the presence of media in which sol-gel samples had been immersed.

Antimicrobial-loaded coatings showed strong activity against a wide range of clinically relevant bacterial and fungal pathogens with no loss of activity from antibiotic alone. The sol-gel coating demonstrated controlled release of antimicrobials and initial sol-gel coatings showed no loss of viability on MSCs with gentamicin containing coatings. Current work is underway investigating cytotoxicity of sol-gel compositions against MG-63 cells and primary osteoblasts.

This research forms part of an extended study into a promising antimicrobial delivery strategy to prevent PJI. The implant coating has potential to advance PJI infection prevention, reducing future burden upon healthcare costs and patient wellbeing.

Articulating cartilage experiences a multitude of biophysical cues. Due to its primary function in distributing load with near frictionless articulation, it is clear that a major stimulus for cartilage homeostasis and regeneration is the mechanical load it experiences on a daily basis. While these effects are considered when performing in vivo studies, in vitro studies are still largely performed under static conditions. Therefore, an increasing complexity of in vitro culture models is required, with the ultimate aim to recreate the articulating joint as accurately as possible. We have for many years utilized a complex multiaxial load bioreactor capable of applying tightly regulated compression and shear loading protocols. Using this bioreactor, we have been able to demonstrate the mechanical induction of human bone marrow stromal cell (BMSC) chondrogenesis in the absence of exogenous growth factors. Building on previous bioreactor studies that demonstrated the mechanical activation of endogenous TGFβ, and subsequent chondrogenesis of human bone marrow derived MSCs, we have been further increasing the complexity of in vitro models. For example, the addition of high molecular weight hyaluronic acid, a component of synovial fluid, culture medium leads to reduced hypertrophy and increased glycosaminoglycan deposition. The ultimate aim of all of these endeavors is to identify promising materials and therapies during in vitro/ ex vivo studies, therefore reducing the numbers or candidates that are finally tested using in vivo studies. This 3R approach can improve the opportunities for success while leading to more ethically acceptable product development pathways.

Spinal diseases such as unstable fractures, infections, primary or secondary tumors or deformities require surgical stabilization with implants. The long-term success of this treatment is only ensured by a solid bony fusion. The size of the bony defect, the often poor bone quality and metabolic diseases increase the risk of non-union and make the case a great burden for the patient and a challenge for the surgeon. The goal of spinal fusion can only be achieved if the implants used offer sufficient mechanical stability and the local biological regeneration potential is large enough to form sufficient bone. The lecture will present challenging clinical cases. In addition, implant materials and new surgical techniques are discussed. Local therapeutic effects are achieved through the release of osteopromotive or anti-resorbtive drugs, growth factors and antibiotics. By influencing biological pathways, basic orthopedic research has strong potential to further positively change future spinal surgery.

Septic arthritis following anterior cruciate ligament reconstruction (ACLR) is a rare and serious complication. Previous studies have shown that septic arthritis is associated with inferior outcome of ACLR. Despite that, there is no standardized treatment protocol, and the course of the disease has mainly been studied within single institutions with a small number of patients.

The aim of the present study is to describe the course of septic arthritis following ACLR in a large nationwide cohort. The hypothesis was that the clinical presentation of septic arthritis following ACLR varies according to the infectious agent.

The present cohort represents patients with septic arthritis identified in a previous study that analyzed compensation claims reported to the Swedish national insurance company (Löf) in 2005–2014 (1). The diagnosis was confirmed by medical experts at Löf after review of medical records. We conducted a comprehensive analysis of the medical records as well as data available from the Swedish National Knee Ligament Registry (SNKLR) for the study group.

The study involved 158 patients who received compensation due to developing septic arhtirits. 94 (59.9%) patients were infected with Coagulase negative staphylococci (CoNS), and 25 patients by Staphyolococcus Aureus (S.Aureus) (15.9%). There was a significant difference between the groups regarding Maximum CRP (p<0.001), and duration between ACLR and first washout operation (p<0.005). S.aureus group had the higest maximum CRP (281) and the shortest duration between ACLR and first washout operation (12 days).

The Clinical presentation of septic arthritis following ACLR can vary according to the agent causing the infection, and low virulent agents are responsible for the majority of the infections. Clinicians need to be aware of these differences and consider them when making diagnosis or treatment decisions.

Glenohumeral joint injuries frequently result in shoulder instability. However, the biomechanical effect of cartilage loss on shoulder stability remains unknown. The aim of the current study was to investigate biomechanically the effect of two severity stages of cartilage loss in different dislocation directions on shoulder stability. Joint dislocation was provoked for 11 human cadaveric glenoids in seven different dislocation directions between 3 o'clock (anterior) to 9 o'clock (posterior) dislocation. Shoulder stability ratio (SSR) and concavity gradient were assessed in intact condition, and after 3 mm and 6 mm simulated cartilage loss. The influence of cartilage loss on SSR and concavity gradient was statistically evaluated. Between intact state and 6 mm cartilage loss, both SSR and concavity gradient decreased significantly in every dislocation direction (p≤0.038), except the concavity gradient in 4 o'clock dislocation direction (p=0.088). Thereby, anterior-inferior dislocation directions were associated with the highest loss of SSR and concavity gradient of up to 59.0% and 49.4%, respectively, being significantly higher for SSR compared to all other dislocation directions (p≤0.04). The correlations between concavity gradient and SSR for pooled dislocation directions were significant for all three conditions of cartilage loss (p<0.001). From a biomechanical perspective, articular cartilage of the glenoid contributes significantly to the concavity gradient, correlating strongly with the associated loss in glenohumeral joint stability. The highest effect of cartilage loss was observed in anterior-inferior dislocation directions, suggesting that surgical intervention should be considered for recurrent shoulder dislocations in the presence of cartilage loss.

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.

Degenerative disc disease, associated to low back pain, afflicts more than 50% of humans, and represents a major healthcare problem, especially for the pathology initiation. Current treatments range from conservative strategies to more invasive surgical techniques, such as disc removal and vertebral fusion. In the Intervertebral Disease (IVD) the nucleus pulposus (NP) degeneration is a key factor for the pathology initiation. Several tissue engineering approaches aiming to restore the appropriate NP cell (NPCs) and matrix content, were attempted by using adult stromal cells either from bone marrow or adipose tissue, chondrocytes, notochordal cells and more recently also pluripotent stem cells. However, none was fully satisfactory since the NP acid and a-vascularized environment appeared averse to the implanted heterologous cells. Several studies demonstrated the efficacy of platelet derivatives such as platelet rich plasma (PRP) in promoting the regeneration of connective tissues. We investigated the efficacy of PRP on NPCs proliferation and differentiation with the goal to propose the direct stimulation of resident cells (stimulation of endogenous cells – less invasive surgical procedure) or the implantation of NPCs expanded in vitro in the presence of PRP as therapeutic agents in IVD degeneration.

NPCs were isolated from small fragments of NP explants, cultivated in medium supplemented with PRP or FCS (standard condition control) and characterized by FACS analysis for the expression of the typical mesenchymal stem cells markers CD34, CD44, CD45, CD73, CD90 and CD105. NPCs cultured in PL showed a phenotypic profile like the cells cultured in FCS. However, compared to NPCs expanded in the presence of FCS, NPCs expanded in PRP showed a much better proliferation and differentiation capacity. NPCs differentiation was evaluated by the cell ability to produce an organized metachromatic cartilaginous matrix, confirmed by the positive immunohistochemical staining for chondrogenic markers.

Matrix-bound vesicles (MBVs) are embedded within osteoid and function as the site of initial mineral formation. However, they remain insufficiently characterised in terms of biogenesis, composition and function while their relationship with secreted culture medium EVs (sEVs) such as exosomes remains debated. We aimed to define the biogenesis and pro-mineralisation capacity of MBVs and sEVs to understand their potential in regenerative orthopaedics.

sEVs and MBVs isolated from conditioned medium (differential ultracentrifugation) and ECM (collagenase digestion and differential ultracentrifugation) of mineralising MC3T3 pre-osteoblast and human bone marrow MSC cultures were characterised by nanoparticle tracking analysis, western blotting, nano-flow cytometry, super resolution microscopy (ONI) and TEM. Immunoprecipitated populations positive for alkaline phosphatase (ALP), a putative marker of mineralisation capacity, were also characterised. Collagen binding efficiency was evaluated using MemGlow staining.

Results reported were comparative across both cell lines. Western blots indicated MBV fractions were positive for markers of endosomal biogenesis (CD9, CD81, ALIX, TSG101) and pro-mineralising proteins (ALP, Pit1, Annexin II, Annexin V), with Annexin V and CD9 present in immunoprecipitated ALP-positive fractions. MBVs were significantly larger than sEVs (p<0.05) and contained a higher amount of ALP (p<0.05) with a significant increase from day 7 to day 14 of cellular mineralisation (p<0.05). This mirrored the pattern of electron-dense vesicles seen via TEM. Super resolution single vesicle analysis revealed for the first-time co-expression of ALP with markers of endosomal biogenesis (CD9, CD63, CD81, ALIX) and Annexin II in both vesicle types, with higher co-expression percentage in MBVs than sEVs. MBVs also exhibited preferential collagen binding.

Advanced imaging methods demonstrated that contrary to opinions in the field, MBVs appear to possess exosomal markers and may arise via endosomal biogenesis. However, it was evident that a higher proportion of MBVs possessed machinery to induce mineralisation and were enriched in mineral-dense material.

Freehand distal interlocking of intramedullary nails remains a challenging task. If not performed correctly it can be a time consuming and radiation expensive procedure. Recently, the AO Research Institute developed a new training device for Digitally Enhanced Hands-on Surgical Training (DEHST) that features practical skills training augmented with digital technologies, potentially improving surgical skills needed for distal interlocking. Aim of the study: To evaluate weather training with DEHST enhances the performance of novices without surgical experience in free-hand distal nail interlocking compared to a non-trained group of novices.

20 novices were assigned in two groups and performed distal interlocking of a tibia nail in an artificial bone model. Group 1: DEHST trained novices (virtual locking of five nail holes during one hour of training). Group 2: untrained novices without DEHST training. Time, number of x-rays, nail hole roundness, critical events and success rates were compared between the groups.

Time to complete the task (sec.) and x-ray exposure (µGcm2) were significantly lower in Group1 414.7 (290–615) and 17.8 (9.8–26.4) compared to Group2 623.4 (339–1215) and 32.6 (16.1–55.3); p=0.041 and 0.003. Perfect circle roundness (%) was 95.0 (91.1–98.0) in Group 1 and 80.8 (70.1–88.9) in Group 2; p<0.001. In Group 1 90% of the participants achieved successful completion of the task (hit the nail with the drill), whereas only 60% of the participants in group 2 achieved this; p=0.121.

Training with DEHST significantly enhances the performance of novices without surgical experience in distal interlocking of intramedullary nails. Besides radiation exposure and operation time the com-plication rate during the operation can be significantly reduced.

The most important outcome predictor of Legg-Calvé-Perthes disease (LCPD) is the shape of the healed femoral head. However, the deformity of the femoral head is currently evaluated by non-reproducible, categorical, and qualitative classifications. In this regard, recent advances in computer vision might provide the opportunity to automatically detect and delineate the outlines of bone in radiographic images for calculating a continuous measure of femoral head deformity. This study aimed to construct a pipeline for accurately detecting and delineating the proximal femur in radiographs of LCPD patients employing existing algorithms. To detect the proximal femur, the pretrained stateof-the-art object detection model, YOLOv5, was trained on 1580 manually annotated radiographs, validated on 338 radiographs, and tested on 338 radiographs. Additionally, 200 radiographs of shoulders and chests were added to the dataset to make the model more robust to false positives and increase generalizability. The convolutional neural network architecture, U-Net, was then employed to segment the detected proximal femur. The network was trained on 80 manually annotated radiographs using real-time data augmentation to increase the number of training images and enhance the generalizability of the segmentation model. The network was validated on 60 radiographs and tested on 60 radiographs. The object detection model achieved a mean Average Precision (mAP) of 0.998 using an Intersection over Union (IoU) threshold of 0.5, and a mAP of 0.712 over IoU thresholds of 0.5 to 0.95 on the test set. The segmentation model achieved an accuracy score of 0.912, a Dice Coefficient of 0.937, and a binary IoU score of 0.854 on the test set. The proposed fully automatic proximal femur detection and segmentation system provides a promising method for accurately detecting and delineating the proximal femoral bone contour in radiographic images, which is necessary for further image analysis.

Osteosarcoma and other types of bone cancers often require bone resection, and backfill with cement. A novel silorane-based cement without PMMA's drawbacks, previously developed for dental applications, has been reformulated for orthopedic use. The aim of this study is to assess each cement's ability to elute doxorubicin, maintain its potency, and maintain suitable weight-bearing strength.

The silorane-based epoxy cement was synthesized using a platinum-based Lamoreaux's catalyst. Four groups of cement were prepared. Two PMMA groups, one without any additives, one with 200 mg of doxorubicin. Two silorane groups: one without any additive, one with doxorubicin, added so that the w% of drug into both cements were equal. Pellets 6 × 12 mm were used for testing (ASTM F451). n=10. Ten pellets from each group were kept dry. All others were placed into tubes containing 2.5 mL of PBS and stored at 37 °C. Elution from doxorubicin-containing groups were collected every day for 7 days, with daily PBS changeout. Antibiotic concentrations were determined via HPLC. Compressive strength and compressive modulus of all groups were determined for unsoaked specimens, and those soaked for 7 and 14 days. MTT assays were done using an MG63 osteosarcoma cell line.

Both cements were able to elute doxorubicin over 7 days in clinically-favorable quantities. For PMMA samples, the incorporation of doxorubicin was shown to significantly affect the compressive strength and modulus of the samples (p<0.01). Incorporation of doxorubicin into silorane had no significant effect on either (p>.05). MTT assays indicated that doxorubicin incorporated into the silorane cement maintained its effectiveness whereas that into PMMA did not. At the dosing used, both cements remained above the 70 MPa.

Both PMMA and silorane-based cements can deliver doxorubicin. Doxorubicin, however, interacts chemically with PMMA, inhibiting polymerization and lowering the chemotherapeutic's effectiveness.

It is known that the gait dynamics of elderly substantially differs from that of young people. However, it has not been well studied how this age-related gait dynamics affects the knee biomechanics, e.g., cartilage mechanical response. In this study, we investigated how aging affects knee biomechanics in a female population using subject-specific computational models.

Two female subjects (ages of 23 and 69) with no musculoskeletal disorders were recruited. Korea National Institute for Bioethics Policy Review Board approved the study. Participants walked at a self-selected speed (SWS), 110% of SWS, and 120% of SWS on 10 m flat ground. Three-dimensional marker trajectories and ground reaction forces (Motion Analysis, USA), and lower limbs’ muscle activities were measured (EMG, Noraxon USA). Knee cartilage and menisci geometries were obtained from subjects’ magnetic resonance images (3T, GE Health Care). An EMG-assisted musculoskeletal finite element modeling workflow was used to estimate knee cartilage tissue mechanics in walking trials. Knee cartilage and menisci were modeled using a transversely isotropic poroviscoelastic material model.

Walking speed in SWS, 110%, and 120% of SWS were 1.38 m/s, 1.51 m/s, and 1.65 m/s for the young, and 1.21 m/s, 1.34 m/s and 1.46 m/s for the elderly, respectively. The maximum tensile stress in the elderly tibial cartilage was ~25%, ~33%, and ~32% lower than the young at SWS, 110%, and 120% of SWS, respectively. These preliminary results suggest that the cartilage in the elderly may not have enough stimulation even at 20% increases in walking speed, which may be one reason for tissue degeneration. To enhance these findings, further study with more subjects and different genders will investigate how age-related gait dynamics affects knee biomechanics.

Acknowledgments: Australian NHMRC Ideas Grant (APP2001734), KITECH (JE220006)

The computational modelling and 3D technology are finding more and more applications in the medical field. Orthopedic surgery is one of the specialties that can benefit the most from this solution. Three case reports drawn from the experience of the authors’ Orthopedic Clinic are illustraded to highlight the benefits of applying this technology.

Drawing on the extensive experience gained within the authors’ Operating Unit, three cases regarding different body segments have been selected to prove the importance of 3D technology in preoperative planning and during the surgery. A sternal transplant by allograft from a cryopreserved cadaver, the realization of a custom made implant of the glenoid component in a two-stage revision of a reverse shoulder arthroplasty, and a case of revision on a hip prosthesis with acetabular bone loss (Paprosky 3B) treated with custom system. In all cases the surgery was planned using 3D processing software and models of the affected bone segments, printed by 3D printer, and based on CT scans of the patients. The surgical implant was managed with dedicated instruments.

The use of 3D technology can improve the results of orthopedic surgery in many ways: by optimizing the outcomes of the operation as it allows a preliminary study of the bone loss and an evalutation of feasibility of the surgery, it improves the precision of the positioning of the implant, especially in the context of severe deformity and bone loss, and it reduces the operating time; by improving surgeon training; by increasing patient involvement in decision making and informed consent.

3D technology, by offering targeted and customized solutions, is a valid tool to obtain the tailored care that every patient needs and deserves, also providing the surgeon with an important help in cases of great complexity.

Infection of implanted medical devices (biomaterials), like titanium orthopaedic implants, can have disastrous consequences, including removal of the device. These so-called biomaterial-associated infections (BAI) are mainly caused by Staphylococcus aureus and Staphylococcus epidermidis. To prevent biofilm formation using a non-antibiotic based strategy, we aimed to develop a novel permanently fixed antimicrobial coating for titanium devices based on stable immobilized quaternary ammonium compounds (QACs).

Medical grade titanium implants were dip-coated in subsequent solutions of hyperbranched polymer, polyethyleneimine and 10 mM sodium iodide, and ethanol. The QAC-coating was characterized using water contact angle measurements, scanning electron microscopy, FTIR, AFM and XPS. The antimicrobial activity of the coating was evaluated against S. aureus strain JAR060131 and S. epidermidis strain ATCC 12228 using the JIS Z 2801:2000 surface microbicidal assay. Lastly, we assessed the in vivo antimicrobial activity in a mouse subcutaneous implant infection model with S. aureus administered locally on the QAC-coated implants prior to implantation to mimic contamination during surgery.

Detailed material characterization of the titanium samples showed the presence of a homogenous and stable coating layer at the titanium surface. Moreover, the coating successfully killed S. aureus and S. epidermidis in vitro. The QAC-coating strongly reduced S. aureus colonization of the implant surface as well as of the surrounding tissue, with no apparent macroscopic signs of toxicity or inflammation in the peri-implant tissue at 1 and 4 days after implantation.

An antimicrobial coating with stable quaternary ammonium compounds on titanium has been developed which holds promise to prevent BAI. Non-antibiotic-based antimicrobial coatings have great significance in guiding the design of novel antimicrobial coatings in the present, post-antibiotic era.

Acknowledgements: This research was financially supported by the Health∼Holland/LSH-TKI call 2021–2022, project 25687, NACQAC: ‘Novel antimicrobial coatings with stable non-antibiotic Quaternary Ammonium Compounds and photosensitizer technology'.

3D Printed polyether-ether-ketone (PEEK) has gained widespread use in clinical practice due to its excellent biocompatibility, biomechanical compatibility, and personalization. However, pre-printed PEEK implants are not without their flaws, including bioinert, optimization distortion of 3D printing digital model and prosthetic mismatching. Recent advancements in mechanical processing technology have made it possible to print bone implants with PEEK fused deposition, allowing for the construction of mechanically adaptable implants. In this study, we aimed to synthesize silanized polycitrate (PCS) via thermal polymerization and in situ graft it to PEEK surface to construct an elastomer coating for 3D printed PEEK implants (PEEK-PCS). This incorporation of PCS allows the implant to exhibit adaptive space filling ability and stress dispersal. In vivo and in vitro results, PEEK-PCS exhibited exceptional osseointegration and osteogenesis properties along with macrophage M2 phenotypic polarization, inflammatory factors reducing, promotion of osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). Additionally, PEEK-PCS displays good autofluorescence properties in vitro and in vivo, with stable fluorescence for 14 days, suggesting potential bioimaging applications. The study confirms that PEEK in situ grafting with thermo-polymerized PCS elastomers is a viable approach for creating multifunctional (bone defect adaptation, bioimaging, immune regulation, and osseointegration) implants for bone tissue engineering.

Aneurysmal bone cyst (ABC) of the spine is a locally aggressive benign lesion which can be treated by en bloc resection with wide margin to reduce the risk of local recurrence. To avoid morbidity associated with surgery, selective arterial embolization (SAE) can be considered the first-line treatment for ABCs of the spine. We previously introduced the use of autologous bone marrow concentrate (BMC) injection therapy to stimulate bone healing and regeneration in ABC of the spine. In this prospective study we described the clinical and radiological outcomes of percutaneous injection of autologous BMC in a series of patients affected by ABCs of the spine.

Fourteen patients (6 male, 8 female) were treated between June 2014 and December 2019 with BMC injection for ABC of the spine. The mean age was 17.85 years. The mean follow up was 37.4 months (range 12–60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits.

Six patients received a single dose of BMC, five patients received two doses and in three patients three doses of BMC were administered. The mean ossification of the cyst (expressed in Hounsfield units) increased statistically from 43.48±2.36 HU to 161.71±23.48 HU during follow-up time and the ossification was associated to an improvement of the clinical outcomes. The mean ossification over time was significantly higher in patients treated with a single injection compared to patients treated with multiple injections. No significant difference in ossification was found between cervical and non-cervical localization of the cyst. Moreover, the initial size of the cyst was not statistically associated with the degree of ossification during follow-up.

The results of this study reinforce our previous evidence on the use of BMC as a valid alternative for spinal ABC management when SAE is contraindicated or ineffective.

The initial size of the cyst and its localization does not influence the efficacy of the treatment. However, data suggest that BMC injection could be indicated as treatment of choice for spinal ABC in young adolescent women.

Intra-articular cartilage pressure distribution in the knee joint is critical in the understanding of osteoarthritis. Combining personalized statistical modeling of the morphological characteristics with discrete element modeling enables patient-specific predictions of the pressure on the tibial plateau. However, modeling of the meniscus during gait is complicated by the dynamic nature of the structure. Nevertheless, the position of the meniscus has a substantial impact on intra-articular stress distribution. Therefore, the focus of this presentation will be on how modeling of meniscal movement during knee flexion improves insight in general meniscal kinematics for the use in tibiofemoral stress distribution calculations.

Hop tests are used to determine return to sports after ACL reconstruction. They mostly measure distance and symmetry but do not assess kinematics and kinetics. Recently, biomechanical evaluations have been incorporated into these functional jump tests for the better assessment of return to sport. We assessed the sagittal plane range of motion (ROM) of the knee, the deviation axis of rotation (DAOR), and the vertical ground reaction force (vGRF) normalized to body weight in nine healthy participants during the single leg (SLH) and crossover hop tests (COHT).

Participants' leg lengths were measured. Jumping distances were marked in the test area as being 4/5 of the leg length. Four sensors were placed on the thighs, the legs and the feet. These body parts were handled as a single rigid body. Eight 480 Hz cameras were used to capture the movements of these rigid bodies. vGRF at landing were measured using a force plate (Bertec, Inc, USA). The ROM of the knee joint and the DAOR were obtained from kinematic data.

Participants' joint kinematics metrics were similar in within-subjects statistical tests for SLH and COHT. We therefore asked whether the repeated vGRF normalized to body weight will be similar in both legs during these jumps. Joint kinematics metrics however were different in between subjects indicating the existence of a personalized jumping strategy. These hop tests can be recorded at the beginning of the training season for each individual, which can establish a comparative evaluation database for prospective lower extremity injury recovery and return to sport after ACL injury.

7–20 % of the patients with a total knee arthroplasty (TKA) are dissatisfied without an indication for revision. Therapeutic options for this patient population with mostly a lack of quadriceps strength are limited. The purpose of this study is to evaluate the effect of six weeks low load resistance training with blood flow restriction (BFR) on the clinical outcome in these unhappy TKA patients.

Thirty-one unhappy TKA patients (of the scheduled fifty patients) without mechanical failure were included in this prospective study since 2022. The patients participate in a supervised resistance training combined with BFR, two times a week during nine weeks. Patients were evaluated by the Knee Osteoarthritis Outcome Score (KOOS), Knee Society Score: satisfaction (KSSs) and the Pain Catastrophizing Scale (PCS). Functionality was tested using the Six Minute Walk Test (6MWT) and the 30-Second Chair Stand Test (30CST). Follow-up took place at six weeks, three months and six months after the start.

Six weeks training with BFR provided statistically significant improvements in all the KOOS subscales compared to the baseline, especially for symptoms (55.1 (±15.4) versus 48.0 (±16.5); p<0.001), activities in daily living (50.3 (±21.1) versus 43.7 (±17.2); p<0.00) and quality of life (24.6 (±18.5) versus 17.3 (±13.0); p<0.001). The PCS reduced from 27.4 (±11.0) to 23.2 (±11.4) at six weeks (p<0.01), whereas the KSSs increased from 11.8 (±6.5) to 14.9 (±7.6) (p=0.021). Both the 6MWT and the 30CST improved statistically significant from respectively 319.7 (±15.0) to 341.6m (±106.5) (p<0.01) and 8.6 (±3.9) to 9.3 times (±4.5) (p<0.01).

Blood flow restriction appears to enhance the quality of life and functional performance of unhappy TKA patients. Based on these preliminary results, BFR seems to be a promising and valuable alternative for these TKA patients with limited therapeutic options.

Treatment of both simple and complex patella fractures is a challenging clinical problem. The aim of this study was to investigate the biomechanical performance of recently developed lateral rim variable angle locking plates versus tension band wiring used for fixation of simple and complex patella fractures.

Twelve pairs of human anatomical knees were used to simulate either two-part transverse simple AO/OTA 34C1 or five-part complex AO/OTA 34C3 patella fractures by means of osteotomies, with each fracture model created in six pairs. The complex fracture pattern was characterized by a medial and a lateral proximal fragment, together with an inferomedial, an inferolateral, and an inferior fragment mimicking comminution around the distal patellar pole. The specimens with simple fractures were pairwise assigned for fixation with either tension band wiring through two parallel cannulated screws, or a lateral rim variable angle locking plate. The knees with complex fractures were pairwise treated with either tension band wiring through two parallel cannulated screws plus circumferential cerclage wiring, or a lateral rim variable angle locking plate.

Each specimen was tested over 5000 cycles by pulling on the quadriceps tendon, simulating active knee extension and passive knee flexion within the range of 90° flexion to full knee extension. Interfragmentary movements were captured via motion tracking.

For both fracture types, the longitudinal and shear articular displacements measured between the proximal and distal fragments at the central patella aspect between 1000 and 5000 cycles, together with the relative rotations of these fragments around the mediolateral axis were all significantly smaller following the lateral rim variable angle locked plating compared with tension band wiring, p<0.01.

Lateral rim locked plating of both simple and complex patella fractures provides superior construct stability versus tension band wiring under dynamic loading.

Intervertebral disc (IVD) degeneration is inadequately understood due to the lack of in vitro systems that fully mimic the mechanical and biological complexity of this organ. We have recently made an advancement by developing a bioreactor able to simulate physiological, multiaxial IVD loading and maintain the biological environment in ex vivo IVD models [1].

To validate this new bioreactor system, we simulated natural spine movement by loading 12 bovine IVDs under a combination of static compression (0.1 MPa), cyclic flexion/extension (±3˚, ±6˚ or 0-6˚) and cyclic torsion (±2˚, ±4˚ or 0-4˚) for more than 10’000 (0.2 Hz) or 100’000 (1 Hz) cycles over 14 days. A higher number of cycles increased the release of glycosaminoglycans and nitric oxide, as an inflammation marker, whereas fewer cycles maintained these two factors at physiological levels. All applied protocols upregulated the expression of MMP13 in the outermost annulus fibrosus (AF), indicating a collagen degradation response. This was supported by fissures observed in the AF after a longer loading duration. Increasing loading cycles induced high cell death in the nucleus pulposus and inner AF, while with fewer cycles, high cell viability was maintained in all IVD regions, irrespective of the magnitude of rotation.

Less frequent multiaxial loading maintains IVD homeostasis while more frequent loading initiates an IVD degenerative profile. Specifically, the morphological and molecular changes were localized in the AF, which can be associated with combined flexion/extension and torsion. More loading cycles induced region-specific cell death and a higher release of extracellular matrix molecules from the innermost IVD regions, likely associated with longer exposure to static compression. Altogether, we demonstrated the advantages of the multiaxial bioreactor to study region-specific response in the IVD, which will allow a more profound investigation of IVD degeneration under different combinations of motions.

Intervertebral disc (IVD) degeneration is responsible for severe clinical symptoms including chronic back pain. Galectins are a family of carbohydrate-binding proteins, some of which can induce functional disease markers in IVD cells and other musculoskeletal diseases. Galectins −4 and −8 were shown to trigger disease-promoting activity in chondrocytes but their effects on IVD cells have not been investigated yet. This study elucidates the role of galectin-4 and −8 in IVD degeneration.

Immunohistochemical evidence for the presence of galectin-4 and −8 in the IVD was comparatively provided in specimens of 36 patients with spondylochondrosis, spondylolisthesis, or spinal deformity. Confocal microscopy revealed co-localization of galectin-4 and −8 in chondrocyte clusters of degenerated cartilage. The immunohistochemical presence of galectin-4 correlated with histopathological and clinical degeneration scores of patients, whereas galectin-8 did not show significant correlations. The specimens were separated into annulus fibrosus (AF), nucleus pulposus (NP) and endplate, which was confirmed histologically. Separate cell cultures of AF and NP (n=20) were established and characterized using cell type-specific markers. Potential binding sites for galectins including sialylated N-glycans and LacdiNAc structures were determined in AF and NP cells using LC/ESI-MS-MS. To assess galectin functions, cell cultures were treated with recombinant galectin-4 or −8, in comparison to IL-1β, and analyzed using RT-qPCR and In-cell Western blot. In vitro, both galectins triggered the induction of functional disease markers (CXCL8 and MMP3) on mRNA level and activated the nuclear factor-kB pathway. NP cells were significantly more responsive to galectin-8 and Il-1β than AF cells. Phosphorylation of p-65 was time-dependently induced by both galectins in both cell types to a comparable extent.

Taken together, this study provides evidence for a functional role of glycobiological processes in IVD degeneration and highlights galectin-4 and −8 as regulators of pro-inflammatory and degrative processes in AF and NP cells.

Patients with bone and muscle weakness from disuse have higher risk of fracture and worse post-injury mortality rates. The goal of this current study was to better inform post-fracture rehabilitation strategies by investigating if physical remobilization following disuse by hindlimb unloading improves osteochondral callus formation compared to continued disuse by hindlimb suspension (HLS). We hypothesized that continued HLS would impair callus bone and cartilage formation and that physical rehabilitation after HLS would increase callus properties.

All animal procedures were approved by the VCU IACUC. Skeletally mature, male and female C57BL/6J mice (18 weeks) underwent HLS for 3 weeks. Mice then had their right femur fractured by open surgical dissection (stabilized with 24-gauge pin). Mice were then either randomly assigned to continued HLS or allow normal physical weight-bearing remobilization (HLS + R). Mice allowed normal cage activity throughout the experiment served as controls (GC). All mice were sacrificed 14-days following fracture with 4-8 mice (male and female) per treatment. Data analyzed by respective ANOVA with Tukey post-hoc (*p< 0.05; # p < 0.10)

Male and female mice showed conserved and significant decreases in hindlimb callus bone formation from continued HLS versus HLS + R. Combining treatment groups regardless of mouse sex, histological analyses using staining on these same calluses demonstrated that HLS resulted in trends toward decreased cartilage cross-sectional area and increased osteoclast density in woven bone versus physically rehabilitated mice.

In support of our hypothesis, physical remobilization increases callus bone formation following fracture compared to continued disuse potentially due to increased endochondral ossification and decreased bone resorption. In all, partial weight-bearing exercise immediately following fracture may improve callus healing compared to delayed rehabilitation regimens that are frequently used.

The interleukin-6/gp130-associated Janus Kinases/STAT3 axis is known to play an important role in mediating inflammatory signals, resulting in production of matrix metalloproteinase-3 (MMP-3). The hip joints with rapidly destructive coxopathy (RDC) demonstrate rapid chondrolysis, probably by increased production of MMP-3 observed in the early stage of RDC. In the recent study, no apparent activation of STAT3 has been shown in the synovial tissues obtained from the osteoarthritic joint at operation. However, no data are currently available on STAT3 activation in the synovial tissues in the early stage of RDC. This study aimed to elucidate STAT3 activation in the synovial tissues in the early stage of RDC. Synovial tissues within 7 months from the disease onset were obtained from four RDC patients with femoral head destruction and high serum levels of MMP-3. RDC synovial tissues showed the synovial lining hyperplasia with an increase of CD68-positive macrophages and CD3-positive T lymphocytes. STAT3 phosphorylation was found in the synovial tissues by immunohistochemistry using anti-phospho-STAT3 antibody. The majority of phospho-STAT3-positive cells were the synovial lining cells and exhibited negative expression of macrophage or T cell marker. Treatment with tofacitinib, a Janus Kinase inhibitor, resulted in a decrease in phospho-STAT3-positive cells, especially with high intensity, indicating effective suppression of STAT3 activation in RDC synovial tissues. Inhibitory effect of tofacitinib could act through the Janus Kinase/STAT3 axis in the synovial tissues in the early stage of RDC. Therefore, STAT3 may be a potential therapeutic target for prevention of joint structural damage in RDC.

Acknowledgements: This study was supported by Katakami Foundation for Clinical Research.

The National Hip Fracture Database (NHFD) is a clinically led web based audit used to inform national policy guidelines. The aim of this audit was to establish the accuracy of completion of NHFD v13.0 theatre collection sheets, identify common pitfalls and areas of good practice, whilst raising awareness of the importance of accuracy of this data and the manner in which it reflects performance of CAH Trauma & Orthopaedic unit in relation to national guidelines. Our aim was to improve completion up to >80% by the operating surgeon and improve overall accuracy.

The methodology within both cycles of the audit were identical. It involved reviewing the NHFD V13.0 completed by the operating surgeon and cross-checking their accuracy against clinical notes, operation notes, imaging, anaesthetic charts and A&E admission assessment.

Following completion of cycle 1 these results were presented, and education surrounding V13.0 was provided, at the monthly trust audit meeting. At this point we introduced a sticker onto the pre-operative checklist for Hip fractures. This included time of admission and reason for delay. We then completed a re-audit.

Cycle-1 included 25 operations, 56% (n=14) had a completed V13.0 form. Of these 21% (n=3) were deemed to be 100% accurate. Cycle-2 included 31 operations (between April – June 21) 81% (n=25) had a completed intra-operative from and showed an increase in accuracy to 56% (n=14)

Through raising awareness, education and our interventions we have seen a significant improvement in the completion and accuracy of v13.0. Although 100% accuracy was not achieved its clear that education and intervention will improve compliance over time.

Through the interventions that we have implemented we have shown that it is possible to improve completion and accuracy of the NHFD V13.0 theatre collection sheet locally and feel this could be implemented nationally.

Mincing cartilage with commercially available shavers is increasingly used for treating focal cartilage defects. This study aimed to compare the impact of mincing bovine articular cartilage using different shaver blades on chondrocyte viability.

Bovine articular cartilage was harvested using a scalpel or three different shaver blades (2.5 mm, 3.5 mm, or 4.2 mm) from a commercially available shaver. The cartilage obtained with a scalpel was minced into fragments smaller than 1 mm³. All four conditions were cultivated in a culture medium for seven days. After Day 1 and Day 7, metabolic activity, RNA isolation, and gene expression of anabolic (COL2A1, ACAN) and catabolic genes (MMP1, MMP13), Live/Dead staining and visualization using confocal microscopy, and flow cytometric characterization of minced cartilage chondrocytes were measured.

The study found that mincing cartilage with shavers significantly reduced metabolic activity after one and seven days compared to scalpel mincing (p<0.001). Gene expression of anabolic genes was reduced, while catabolic genes were increased after day 7 in all shaver conditions. The MMP13/COL2A1 ratio was also increased in all shaver conditions. Confocal microscopy revealed a thin line of dead cells at the lesion site with viable cells below for the scalpel mincing and a higher number of dead cells diffusely distributed in the shaver conditions. After seven days, there was a significant decrease in viable cells in the shaver conditions compared to scalpel mincing (p<0.05). Flow cytometric characterization revealed fewer intact cells and proportionally more dead cells in all shaver conditions compared to the scalpel mincing.

Mincing bovine articular cartilage with commercially available shavers reduces the viability of chondrocytes compared to scalpel mincing. This indicates that mincing cartilage with a shaver should be considered a matrix rather than a cell therapy. Further experimental and clinical studies are required to standardize the mincing process with a shaver.

Acknowledgements: This study received unrestricted funding from KARL STORZ SE & Co. KG.

This study aimed to characterise the microarchitecture of bone in different species of animal leading to the development of a physiologically relevant 3D printed cellular model of trabecular (Tb) and cortical bone (CB). Using high resolution micro-computed tomography (μ-CT) bone samples from multiple species were scanned and analysed before creating in silico models for 3D printing. Biologically relevant printing materials with physical characteristics similar to that of in vivo bone will be selected and tested for printability.

Porcine and murine bone samples were scanned using μ-CT, with a resolution of 4.60 μM for murine and 11 μM for porcine and reconstructed to determine the architectural properties of both Tb and CB independently. A region of interest, 1 mm in height, will be used to generate an in-silico 3D model with dimensions (10 mm³) and suitable resolution before being translated into printable G code using CAD assisted software.

A 1 mm section of each bone was analysed, to determine the differences in the microarchitecture with the intent of setting a benchmark for the developmental 3D in vitro model to be comparable against. In contrast, porcine caudal vertebrae (PCV) have an increased volume due to the size of the bone sample. Interestingly, BV/TR for Tb is similar between species in all samples except murine femur. Murine tibia and PCV have a similar Tb. number and thickness, however different SMI shape and separation.

μ-CT scanning and analysis permits tessellation of the 3D output which will lead to the generation of an in silico printable model. Biomaterials are currently under optimisation to allow printability and shape integrity to reflect the morphological and physiological properties of bone.

Macrophages (Mφ) are immune cells that play a crucial role in both innate and adaptive immunity as they are involved in a wide range of physiological and pathological processes. Depending on the microenvironment and signals present, Mφ can polarize into either M1 or M2 phenotypes, with M1 macrophages exhibiting pro-inflammatory and cytotoxic effects, while M2 macrophages having immunosuppressive and tissue repair properties. Macrophages have been shown to play key roles in the development and progression or inhibition of various diseases, including cancer. For example, macrophages can stimulate tumor progression by promoting immunosuppression, angiogenesis, invasion, and metastasis. This work aimed to investigate the effect of extracellular vesicles (EVs)-derived from polarized macrophages on an osteosarcoma cell line. Monocytes were extracted from buffy coats and cultured in RPMI medium with platelet lysate or M-CSF. After 6 days of seeding, Mφ were differentiated into M1 and M2 with INF-γ/LPS and IL-4/IL-13, respectively. The medium with M1 or M2 derived EVs was collected and EVs were isolated by differential centrifugation and size exclusion chromatography and its morphology and size were characterized with SEM and NTA, respectively. The presence of typical EVs markers (CD9, CD63) was assessed by Western Blot. Finally, EVs from M1 or M2-polarized Mφ were added onto osteosarcoma cell cultures and their effect on cell viability and cell cycle, proliferation, and gene expression was assessed. The EVs showed the typical shape, size and surface markers of EVs. Overall, we observed that osteosarcoma cells responded differentially to EVs isolated from the M1 and M2-polarized Mφ. In summary, the use of Mφ-derived EVs for the treatment of osteosarcoma and other cancers deserves further study as it could benefit from interesting traits of EVs such as low immunogenicity, nontoxicity, and ability to pass through tissue barriers.

Acknowledgements: Carlos III Health Institute and the European Social Fund for contract CP21/00136 and project PI22/01686.

Elective orthopaedic procedures, and particularly total hip arthroplasty (THA), in octogenarians and nonagenarians patients are burdened of several implications. Besides the comorbidities and the anesthesiological issues, legal and ethical implications are present. Some literature data show the clinical improvement of THA in elderly patient but the psychological aspects are not yet evaluated. Aim of this study is to evaluate the clinical aspects and the psychological impact in daily living in octogenarians and nonagenarians patients addressing THA.

We conducted a retrospective evaluation of 81 THA in 81 patients of age more than 85 years with a minimum follow-up of 6 months. Clinical aspects were evaluated using the Hip disability and Osteoarthritis Outcome Score (HOOS). The psychological issues were evaluated with the Short Form 12 (SF-12) using both the Physical Component Summary (PCS) and the Mental Component Summary (MCS). From the starter cohort of 81 patients, 8 patients were died for causes unrelated to surgery, 13 were lost to follow-up, 1 patient was revised for periprosthetic fracture; 59 patients composed the final cohort. Mean HOOS rased from 18,07 ± 17,81 to 92,36 ± 5,74 with statistically significant distribution both in the global score than in all of the different subscales. The PCS raised from 26,81 ± 10,81 to 51,86 ± 4,45 and The MCS raised from 34,84 ± 10,81 to 56,70 ± 5,04, but none of them showed a statistically significant distribution. THA in octogenarians and nonagenarians patients could be a safe procedure with positive results for clinical and psychological aspects.

Robotic assistance in knee arthroplasty has become increasingly popular due to improved accuracy of prosthetic implantation. However, literature on the mid-term outcomes is limited especially that of hand-held robotic-assisted devices. We present one of the longest follow-up series to date using this novel technology and discuss the learning curve for introducing robotic technology into our practice.

The purpose of this single-surgeon study is to evaluate the survival, patient-reported outcomes and learning curve for handheld boundary-controlled robotic-assisted unicompartmental knee arthroplasties (HBRUKAs) at our hospital.

This retrospective study evaluates 100 cases (94 Medial, 6 Lateral) performed by a single surgeon between October 2012 and July 2018. 52% were males, mean age was 64.5y (range 47.3y-85.2y) and mean BMI was 31.3 (range 21.8–43). Both inlay (40%) and onlay (60%) designs were implanted. Patients were followed up routinely at 1 and 5 years with Oxford Knee Scores (OKS) recorded. The learning curve was determined by tourniquet times.

At a mean follow-up of 4.3 years (range 1.6y–7.3y), survivorship was 97%. There were three revisions: One case of aseptic loosening (1.5y), one case of deep-infection (3.8y) and one case of contralateral compartment osteoarthritis progression (5y). Mean 5-year OKS was 39.8. A 14.3% reduction in mean tourniquet times between the first 25 cases (105.5minutes) and subsequent cases (90.4minutes) was seen.

This single-surgeon study showed good survivorship and patient-reported outcomes for HBRUKAs at our hospital. A learning curve of approximately 25 cases was shown, with significant decreases in tourniquet times with respect to increased surgeon experience.

Determine the prevalence, etiologies, and risk factors of unplanned return to the OR (UROR) in adult orthopaedic trauma patients.

Retrospective review of a trauma prospective registry from 2014 – 2019 at a Level 1 academic hospital. An UROR was defined as a patient returning to OR unexpectedly following a planned definitive surgery to either readdress the presenting diagnosis or address a complication arising from the index procedure. Univariate and multivariate logistic regression was performed comparing those patients with an UROR versus those without.

A total of 1568 patients were reviewed. The rate of UROR was 9.8% (153 patients). Symptomatic implant was the leading cause of UROR (60%). Other significant UROR causes were infection (15%) and implant failure (9%). The median time between index procedure and UROR was 301 days.

For the univariate and multivariate analysis, open fracture (p< 0.05), fracture complexity (p<0.01), and weekend procedure (p< 0.01) were all associated with increased risk of UROR. All other variables were not statistically significant for any associations.

Those patients with an UROR for reasons other than symptomatic implants were more likely to have polyorthopaedic injuries (p < 0.05), ISS > 15 (p < 0.05), osteoporosis (p < 0.01), ICU status (p < 0.05), psychiatric history (p < 0.05), compartment syndrome (p < 0.05), neurovascular injury (p < 0.01), open fracture (p < 0.05), and fracture complexity (p < 0.05).

The rate of UROR in the orthopaedic trauma patient population is 10%. Most of these cases are due to implant-related issues. UROR for reasons other than symptomatic implants tend to be polytraumatized patients with higher-energy injuries, multiple complex fractures, and associated soft tissue injuries. Future focus on improved implant development and treatments for polytraumatized patients with complex fractures is warranted to decrease a relatively high UROR rate in orthopaedic trauma.

Due to the presence of megakaryocytes, platelets and clotting factors, bone marrow aspirate (BMA) tends to coagulate. For the first time, starting from our previous studies on mesenchymal vertebral stem cells, it has been hypothesized that coagulated BMA represents a safe and effective autologous biological scaffold for bone regeneration in spinal surgery. The present research involved advanced preclinical in vitro models and the execution of a pilot clinical study.

Evaluation of cell morphology, growth kinetics, immunophenotyping, clonogenicity, trilineage-differentiation, growth-factors and HOX and TALE gene expression were analyzed on clotted- and un-clotted human V-BMA. In parallel, a pilot clinical study on ten patients with degenerative spine diseases submitted to instrumented posterior arthrodesis, is ongoing to assess the ability of clotted-V-BMA to improve spinal fusion at 6- and 12-months follow-up.

Results demonstrated that clotted-V-BMA have significantly higher growth-factor expression and mesenchymal stem cell (MSCs) viability, homogeneity, clonogenicity, and ability to differentiate towards the osteogenic phenotype than un-clotted-V-BMA. Clotted-V-BMA also highlighted significant reduced expression of PBX1 and of MEIS3 genes negatively involved in osteoblast maturation and differentiation. From December 2020, eight patients have already been enrolled with first promising results that will be finally evaluated in the next two months.

The application of V-BMA-clot as carrier of progenitors and cytokines and as natural scaffold with a structural texture represents a point-of-care orthobiologic product to improve spinal fusion. Clinical application seems to be efficacy, and we will confirm and strengthen these data with the final results of the pilot clinical study.

Variations in pelvic anatomy are a major risk factor for misplaced percutaneous sacroiliac screws used to treat unstable posterior pelvic ring injuries. A better understanding of pelvic morphology improves preoperative planning and therefore minimises the risk of malpositioned screws, neurological or vascular injuries, failed fixation or malreduction. Hence a classification system which identifies the clinically important anatomical variations of the sacrum would improve communication among pelvic surgeons and inform treatment strategy.

300 Pelvic CT scans from skeletally mature trauma patients that did not have pre-existing posterior pelvic pathology were identified. Axial and coronal transosseous corridor widths at both S1 and S2 were recorded. Additionally, the S1 lateral mass angle were also calculated. Pelvises were classified based upon the sacroiliac joint (SIJ) height using the midpoint of the anterior cortex of L5 as a reference point. Four distinct types could be identified:

Differences in transosseous corridor widths and lateral mass angles between classification types were assessed using two-way ANOVAs.

Type-B was the most common pelvic type followed by Type-A, Type-C, and Type-D. Significant differences in the axial and coronal corridors was observed for all pelvic types at each level. Lateral mass angles increased from Types-A to C, but were smaller in Type-D.

This classification system offers a guide to surgeons navigating variable pelvic anatomy and understanding how it is associated with the differences in transosseous sacral corridors. It can assist surgeons’ preoperative planning of screw position, choice of fixation or the need for technological assistance.

AM specifically allows for cost-efficient production of patient-specific Orthopaedic medical devices with unusual designs and properties. A porous design allows to adjust the stiffness of metallic implants to that of the host bone. Beyond traditional metals, like titanium alloys, this talk will review the present state-of-the-art of directly printed absorbable metal families. Physicochemical, mechanical and biological properties of standardized design prototypes from all currently available metal families will be compared and their clinical application potential discussed. The impact of in vitro test environments on comparative corrosion behavior, post manufacturing aspects, and the recent status quo in biocompatibility testing and present knowledge gaps will be addressed.

The aim of this work was to develop a novel, accessible and low-cost method, which is sufficient to measure changes in meniscal position in a whole-knee joint model performing dynamic motion in a knee simulator.

An optical tracking method using motion markers, MATLAB (MATLAB, The MathWorks Inc.) and a miniature camera system (Raspberry Pi, UK) was developed. Method feasibility was assessed on porcine whole joint knee samples (n = 4) dissected and cemented to be used in the simulator (1). Markers were placed on three regions (medial, posterior, anterior) of the medial meniscus with corresponding reference markers on the tibial plateau, so the relative meniscal position could be calculated. The Leeds high kinematics gait profile scaled to the parameters of a pig (1, 2) was driven in displacement control at 0.5 Hz. Videos were recorded at cycle-3 and cycle-50. Conditions tested were the capsule retained (intact), capsule removed and a medial posterior root tear. Mean relative displacement values were taken at time-points relating to the peaks of the axial force and flexion-extension gait inputs, as well as the range between the maximum and minimum values. A one-way ANOVA followed by Tukey post hoc analysis were used to assess differences (p = 0.05).

The method was able to measure relative meniscal displacement for all three meniscal regions. The medial region showed the greatest difference between the conditions. A significant increase (p < 0.05) for the root tear condition was found at 0.28s and 0.90s (axial load peaks) during cycle-3. Mean relative displacement for the root tear condition decreased by 0.29 mm between cycle-3 and cycle-50 at the 0.28s time-point. No statistically significant differences were found when ranges were compared at cycle-3 and cycle-50.

The method was sensitive to measure a substantial difference in medial-lateral relative displacement between an intact and a torn state. Meniscus extrusion was detected for the root tear condition throughout test duration. Further work will progress onto human specimens and apply an intervention condition.

Fractures of the prosthetic components after total knee arthroplasty (TKA) are rare but dangerous complications, sometimes difficult to diagnose and to manage. Aim of this study is to evaluate the incidence of component breakage and its treatment in our single institution's experience. We retrospectively review our institution registry. From 605 revision knee arthroplasties since 2000 to 2018, we found 8 cases of component breakage, of these 3 belonged to UKA, and 5 belonged to TKA. The UKA fractures were all on the metal tibial component; while 4 TKA fractures were ascribed to the liner (2 Posterior-Stabilized designs and 2 constrained designs) and only one case was on the femoral component. For every patient a revision procedure was performed, in two cases a tibial tubercle osteotomy was performed, while in one case (where the fracture was of the post cam) an arthroscopy was performed prior to the arthrotomy. All of the UKA fractures were treated with a standard revision implant. As regard the TKA, 2 liner fractures were treated with the only liner exchange, while the other 2 liner fractures and the fracture of the metallic component were treated with total knee revision. No intra- and post-operative complications were found. Component breakage after TKA is a serious complication. Its treatment, always surgical, can hide pitfalls, especially if the timing is not correct; indeed apart from the revision of one or more components, the surgeons must address any issues of management of bone defect and ligamentous stability.