Background. Simply stated, carbon reinforced carbon (C/C) may be considered as fibre reinforced pyrocarbon. Pyrocarbon is used e.g. in finger joints and artificial heart valves. Aim of the present study was to evaluate if C/C could broaden the field of orthopaedic applications compared to pyrocarbon. Technically, C/C is used e.g. for brakes of F-1 race cars. Methods. The mechanical strength of the C/C material was characterised by a biaxial flexural bending test according ISO 6474-1. Three C/C shoulder heads articulating against vitamin E stabilised, highly cross-linked UHMWPE (E-XLPE) underwent a shoulder simulator study up to 106 cycles. The Coefficient of Friction (CoF) of C/C disks (Ra: 0.045 μm) against cartilage was analysed by a reciprocal cartilage wear tester. The test was conducted in cell culture medium for 4 h and 12 h using bovine cartilage. All test data is compared to the corresponding test results with Al2O3 ceramic. Conclusions. The strength of C/C is 30 % lower than that of Al2O3 ceramic. Its wear rate measured in the shoulder simulator against E-XLPE is in tendency higher than that of ceramic heads. The CoF against cartilage is double compared to the same test with Al2O3. - C/C seems to have limited a potential as material for orthopaedic application. However, more investigations and optimisation of the C/C type and quality are necessary. Level of evidence. Laboratory test on material samples. Study financed by Mathys Ltd Bettlach

Total knee arthroplasty is one of the most common surgeries. About 92% of all implanted knee endorposthesis in 2020 were manufactured from uncoated CoCrMo articulating on ultra-high-molecular-weight polyethylene. All articluations generate wear particles and subsequent emission of metal ions due to the mechanical loading. These wear particles cause diverse negative reactions in the surrounding tissues and can lead to implant loosening. Coating technologies might offer the possibility to reduce this wear. Therefore, we investigated the applicability of tetrahedral amorphous carbon (ta-C) coating on CoCrMo alloy. Polished specimens made of CoCrMo wrought alloy according to ISO 5832-12 were coated with ta-C coatings with different layer structure using pulsed laser deposition (PLD). This process allows the deposition of ta-C coatings with low internal stress using an additional relaxation laser. Surface quality and mechanical properties of the coating were characterised using optical surface measurements (NanoFocus μsurf expert, NanoFocus AG) and a nanoindentation tester NHT. 3. (Anton Paar GmbH). Scratch tests were performed on Micro Scratch Tester MST. 3. (Anton Paar TriTec SA) to define the coating adhesion. Pin-on-plate tribological tests, with a polyethylene ball sliding on the ta-C-coated plate under a defined load according to ISO 14243-1 were performed using a linear tribometer (Anton Paar GmbH) to evaluate the tribological and wear properties. The ta-C coatings showed a mean roughness Ra of 5-20 nm and a hardness up to 60 GPa (n=3). The adhesion of the ta-C coatings (n=3) was comparable to the commercial coatings like TiN and TiNbN. The pin-on-plate tests showed an improvement of tribological properties in comparison with the polished uncoated CoCrMo specimens (n=3). The ta-C coatings applied by DLP technology show increased hardness compared to the base material and sufficient adhesion. Further research will be needed to investigate the optimal coating strategy for implant coating

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)

Background. Due to their tailored porous texture, breathability and flexibility, carbon cloths (CCs) are good scaffolds for biomedical application. However, biocompatibility of CCs depends on their physic-chemical properties. Calcium phosphate ceramics (CaP) are well known for their use in orthopaedic field. So, carbon cloth-reinforced CaP composites are promising bioceramic materials for bone regeneration. Methods. CaP coating are performed using sono-electrochemical deposition method. The electrolyte consisted in an aqueous solution of calcium and phosphates precursors. CC was used as work electrode in three-electrode system. SEM, TEM, XRD, 1H and 31P MAS NMR and FTIR spectroscopies were performed to characterise the deposits. In vitro biocompatibility of CCs with and without coatings is tested with human osteoblasts. Results. The current density influences the morphology and the chemical composition of deposit: it consists mainly in carbonated hydroxyapatite with plate-like shape for lower current densities and needle-like shape for the highest. A hydrophobic surface of CC with due to small amount of oxygenated functions leads to a poor biocompatibility. Conclusion. The wettability of CCs is an important parameter of biocompatibility. Biomimetic CaP deposits obtained by sono-electrodeposition present a microstructure and a chemical composition close to the mineral phase of natural bone. This work was supported by Region Centre project: bioactive hybrid materials for bone reconstruction. 2014–2016

Background context. Fusion is a fundamental procedure in spine surgery. Although autogenous grafts have ideal bone graft characteristics, their use may remain limited due to various morbidities. Even though ceramic based synthetic bone grafts are used commonly at present, in order to enhance their efficacy, their combined use with other materials has been investigated. The use of carbon nanotubes (CNTs) together with synthetic bone grafts such as hydroxyapatite (HA) has contributed to positive developments in bone tissue engineering. Purpose. The aim of the present study was to investigate the effect of CNTs/ HA- tricalcium phosphate (TCP) composite prepared in posterolateral spinal fusion model. Study Design/Setting. Experimental animal study. Methods. At first, CNTs and CNTs/HA-TCP composites were prepared. Twenty adult male Spraque Dawley rats were randomized into four groups with five rats in each group. Decortication was carried out in standard manner in all animals. Group 1 (only decortication), group 2 (CNTs), group 3 (HA-TCP) and group 4 (CNTs/HA-TCP) were formed. Eight weeks later all animals were sacrificed and obtained fusion segments were evaluated by manual palpation, histomorphometry and micro computed tomography (mCT). Results. In all evaluations, highest fusion values were obtained in Group 4. In mCT investigations, bone volume/ tissue volume (BV/TV) ratio was found to be significantly higher in composite group (group 4) only compared to ceramic group (group 3). Although in Group 2, in which only CNTs were used, the ratio was found to be significantly higher than group 1, the difference was not considered significant in terms of fusion and in addition in group 2, CNTs were completely surrounded by fibrous tissue, i.e. no bone formation was observed. Conclusions. The combined use of carbon nanotubes with ceramic based bone grafts enhances spinal fusion markedly. Although CNTs are inadequate in producing spinal fusion when they are used by themselves, due to especially their high biocompatibillity and unique bicomechanic characteristics compatible with bone tissue, they increase fusion rates significantly, particularly together with ceramic based synthetic grafts. Keywords. Spinal fusion; Rat; Carbon nanotube(s); Ceramic(s); Bone graft subsitutes; Hydroxyapatite

Introduction. Ten explanted pyrolytic carbon components of a number of finger prostheses were obtained at revision surgery for wear analysis. Implants were removed for either dislocation or failure of fixation. Hypothesis Failure of the components was due to wear from the articulating surfaces, as occurs in many hip and knee prostheses. Methods. The articulating surfaces were examined using a ZYGO NewView 5000 non-contact profilometer with a resolution of 1nm, to determine the roughness average (RA) of the surface. A total of 86 RA measurements were taken. Detailed images of the surface displayed as a 3D map of were acquired. The RA values for each component were averaged and compared against the British standard for orthopaedic implants, which states that the articulating surfaces of devices made of metal or ceramic should have RA values lower than 0.050 µm. Results. The low surface roughness demonstrated that the vast majority of the articulating surfaces of the components were relatively unworn with RA values lower than British standard, even following use in vivo. ZYGO images showed light unidirectional scratching on four of the explanted components, but despite the scratching, the RA values of these components were still low (<0.050 µm) showing that this was superficial damage. No other significant damage was observed. Discussion. Due to the lack of damage on the articulating surfaces and the low RA values recorded the failure of these prostheses is not considered to be wear related. Significance This is the first report of ex vivo analysis of pyrolytic carbon finger prostheses

Summary Statement. Innovative nanocomposite carbon coating doped with Si can significantly improve the osseintegration of orthopaedics implants. Additionally, this kind of coating increases the mechanical resistance of the implants, what is especially important on case of joints (frictional pairs). Introduction. Use of layers of carbon-doped silicon, which leads to the synthesis of layers improving mechanical and biological characteristics, let obtain good strength by volume features. Suitable introduction to the structure of amorphous silicon dioxide layer allow for the production of higher adhesion to metallic substrates and consequently the increased thickness and hardness. The increased thickness of the layer leads to a stronger diffusion barrier to harmful metal ions from the implant material and thus consequently improving the biocompatibility of the implant. Moreover, a silicon beneficial effect on stress relaxation layer formed during the synthesis. This allows for improved biocompatibility, also affects other property obtained in the case of silicon carbide layers, the bacteriastability. This further protects the surface of the implant against the risk of bacterial colonization in both the implantation and subsequent use in the body, and preferably suppressing inflammation and faster healing of surgical wounds. The thus obtained product is much better than the biological and mechanical parameters of currently offered. Patients & Methods. In order to evaluate the fabricated coatings conditions examination of the basic physicochemical and mechanical properties were conducted (AFM, Raman, XPS, nanoindentation technique). The in vitro and in vivo tests were also conducted. As a biological material osteoblast Saos-2 cells and endothelial cells line EA. 926 were used. For the evaluation of proliferation and cytotoxicity a “live/dead” test was used. For testing bactericidal activity of the C/Si coatings, an exponential growth phase of E. coli strain DH5 α was used. Test of bacterial immediate toxicity and bacterial colonization were performed. A model of rabbits and guinea pigs were used to obtained results with reference to irritation, intradermal reactivity, sensitization, local effects after implantation with the histopathological examination, cytotoxicity test. Results. XPS results have shown that the silicon content for each group of samples, both steel and titanium alloy is about 3, 4 and 5 percent. Increasing the concentration of silicon above 5% results in the weakening of the mechanical properties of the layer and lead to delamination of the sterilization process. Addition of silicon in the range of 3–5% does not negatively affect the mechanical and structural properties of the modified surface and from this point of view, all the criterion of strength. Performed studies confirmed very good mechanical properties of C/Si coatings. In vitro studies have indicated the optimal concentration of silicon in the coating, where the material is biocompatible and also has good antibacterial properties. Biocompatibility of silicon coatings was also confirmed by irritation and sensitization testing in the in vivo model. Discussion/Conclusion. Final result of the surface modification C/Si coating depends on modification of two effects, i.e. the formation of the transition layer of the substrate material and the synthesis of the outer carbon coating. Results of in vitro and in vivo tests confirmed very good biological properties of coatings which proved the fact that it is possible to improve the parameters of the implant work at the same time adding to the intrinsic the antibactericidal properties

To date there has been no material for endoprosthetics providing excellent resistance to abrasion and corrosion combined with great tensile strength, fracture toughness, and bending strength, as well as adequate biocompatibility. Carbon-fiber-reinforced silicon carbide (C/SiC, C/C-SiC or C/SiSiC) is as a ceramic compound a potentially novel biomaterial offering higher ductility and durability than comparable oxide ceramics.

Aim of this investigation was to test the suitability of C/SiC ceramics as a new material for bearing couples in endoprosthetics. One essential quality that any new material must possess is biocompatibility. For this project the in-vitro biocompatibility was investigated by using cuboid like scaffolds made of CMC. To determine whether the material is suited as a lubricant partner in endoprosthetics, we measured its abrasion coefficient and wear tolerance against various antibodies. The C/SiC samples tested were produced via the Liquid Silicon Infiltration (LSI) of pyrolized porous fiber preforms made by warm-flow pressing free-flowing granulates on a hydraulic downstroking press with a heated die of the type HPS-S, 1000 kN. After preparation of the composites, the tribological characteristics are determined. Flexural strength was determined at room temperature according to DIN685-3 with an universal testing machine Z100 and the Young”s -modulus was carried out via resonant frequency-damping analysis RFDA. The samples”surface as well as cell adhesion and cell morphology were assessed via ESEM. The human osteoblast-like cell line MG-63 and human ostoeblast were used for cel culture ecperiments (WST, Live/dead, Cytotoxicity, cell morphology). Based on the raw data the mean value and the standard deviation were calculated. The Mann-Whitney-U-Test was used to evaluate the differences between experiment and control samples. The flexural strength at room temperature is approx. 180 MPa, while the elongation at break is about 0.13%. The Young”s modulus is detected between 120 and 150 GPa. The density lies between 2.5 and 3.0 g/cm³. We noted a friction coefficient µ between 0.31. The cell lines exhibited no morphological alterations, and adhered well to the C/SiC samples. Vitality was not impaired by contact with the ceramic composite. Cell growth was observed evenly distributed over a 21-day period. In the future, investigators aiming to apply this composite in endoprosthetics will have to focus on its efficacy in conjunction with sudden, strong demands, and long-term performance in bodily fluids within joint simulators, etc. In conclusion: C/SiC can definitely be considered a new material with genuine potential for use in endoprosthetics.

Knee arthroplasty with a rotating hinge knee (RHK) prosthesis has become an important clinical treatment option for knee revisions and primary patients with severe varus or valgus deformities and instable ligaments. The rotational axle constraints the anterior-posterior shear and varus-valgus moments, but currently used polyethylene bushings may fail in the mid-term due to insufficient creep and wear resistance of the material. Due to that carbon-fibre-reinforced (CFR) PEEK as an alternativ bushing material with enhanced creep, wear and fatigue behaviour has been introduced in a RHK design [Grupp 2011, Giurea 2014]. The objective of our study was to compare results from the pre-clinical biotribological characterisation to ex vivo findings on a series of retrieved implants.

In vitro wear simulation according to ISO 14243-1 was performed on rotating hinge knee devices (EnduRo® Aesculap, Germany) made out of cobalt-chromium and of a ZrN multi-layer ceramic coating for 5 million cycles. The mobile gliding surfaces were made out of polyethylene (GUR 1020, β-irradiated 30 ± 2 kGy). For the bushings of the rotational and flexion axles and the flanges a new bearing material based on CFR-PEEK with 30% PAN fiber content was used.

Analysis of 12 retrieved EnduRo^® RHK systems in cobalt-chromium and ZrN multi-layer in regard to

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loosening torques in comparison with initial fastening torques

with a focus on the four CFR-PEEK components integrated in the EnduRo^® RHK design.

For the rotating hinge knee design with flexion bushing and flanges out of CFR-PEEK the volumetric wear rates were 2.3 ± 0.48 mm³/million cycles (cobalt-chromium) and 0.21 ± 0.02 mm³/million cycles (ZrN multi-layer), a 10.9-fold reduction (p = 0.0016). The UHMWPE and CFR-PEEK particles were comparable in size and morphology and predominantly in submicron size [5]. The biological response to representative sub-micron sized CFR-PEEK particles has been demonstrated in vivo based on the leucoyte-endothelian-cell interactions in the synovia of a murine intra-articular knee model by Utzschneider 2010. Schwiesau 2013 extracted the frequency of daily activities in hip and knee replacement patients from literature and estimated an average of 1.76 million gait cycles per year. Thus, the 5 million cycles of in vitro wear testing reflect a mean in vivo service life of 2.9 years, which fits to the time in vivo of 12–60 months of the retrieved RHK devices. The in vitro surface articulation pattern of the wear simulation tests are comparable to findings on retrieved CFR-PEEK components for both types of articulations – cobalt-chromium and ZrN multi-layer coating.

For the rotating hinge knee design the findings on retrieved implants demonstrate the high suitability of CFR-PEEK as a biomaterial for highly loaded bearings, such as RHK bushings and flanges in articulation to cobalt-chromium and to a ZrN multi-layer coating.

The inability to replace human muscle in surgical practice is a significant challenge. An artificial muscle controlled by the nervous system is considered a potential solution for this. We defined it as neuromuscular prosthesis. Muscle loss and dysfunction related to musculoskeletal oncological impairments, neuromuscular diseases, trauma or spinal cord injuries can be treated through artificial muscle implantation. At present, the use of dielectric elastomer actuators working as capacitors appears a promising option. Acrylic or silicone elastomers with carbon nanotubes functioning as the electrode achieve mechanical performances similar to human muscle in vitro. However, mechanical, electrical, and biological issues have prevented clinical application to date. In this study, materials and mechatronic solutions are presented which can tackle current clinical problems associated with implanting an artificial muscle controlled by the nervous system. Progress depends on the improvement of the actuation properties of the elastomer, seamless or wireless integration between the nervous system and the artificial muscle, and on reducing the foreign body response. It is believed that by combining the mechanical, electrical, and biological solutions proposed here, an artificial neuromuscular prosthesis may be a reality in surgical practice in the near future

Serial section electron microscopy (SSEM) was initially developed to map the neural connections in the brain. SSEM eventually led to the term ‘Connectomics’ to be coined to describe process of following a cell or structure through a volume of tissue. This permits the true three-dimensionality to be appreciated and relationships between cells and structures. The purpose of this study was to utilize this methodology to interrogate S. aureus infected bone. Bone samples were harvested from mice tibia infected with S. aureus and were fixed, decalcified, and osmicated. The samples were paraffin embedded and 5-micron sections were cut to identify regions of bacterial invasion into the osteocyte-lacuna-canalicular-network (OLCN). This area was cut from the paraffin block, deparaffinized, post-fixed and reprocessed into epoxy resin. Serial sections were cut at 60nm and collected onto Kapton tape utilizing the Automated Tape-collecting Ultramicrotome (ATUMtome) system. Samples were mounted onto 4” silicon wafers and post-stained with 2% uranyl acetate followed by 0.3% lead citrate and carbon coated. A ZEISS GeminiSEM 450 scanning electron microscope fitted with an electron backscatter diffusion detector was used to image the sections. The image stack was aligned and segmented using the open-source software, VASTlite. 264 serial sections were imaged, representing approximately 40 × 45 × 15-micron (x, y, z) volume of tissue. 70% of the canaliculi demonstrated infiltration by S. aureus. This study demonstrates that SSEM can be applied to the skeletal system and provide a new solution to investigate the OLCN system. It is feasible that this methodology could be implemented to investigate why some canaliculi are resistant to colonization and potentially opens up a new direction for the prevention of chronic osteomyelitis. In order to make this a realistic target, automated segmentation methodologies utilizing machine learning must be developed and applied to the bone tissue datasets

The periclavicular space is a conduit for the brachial plexus and subclavian-axillary vascular system. Changes in its shape/form generated by alteration in the anatomy of its bounding structures, e.g. clavicle malunion, cause distortion of the containing structures, particularly during arm motion, leading to syndromes of thoracic outlet stenosis etc., or alterations of scapular posture with potential reduction in shoulder function. Aim of this study was developing an in vitro methodology for systematic and repeatable measurements of the clinically poorly characterized periclavicular space during arm motion using CT-imaging and computer-aided 3D-methodologies. A radiolucent frame, mountable to the CT-table, was constructed to fix an upper torso in an upright position with the shoulder joint lying in the isocentre. The centrally osteotomized humerus is fixed to a semi-circular bracket mounted centrally at the end of the frame. All arm movements (ante-/retroversion, abduction/elevation, in-/external rotation) can be set and scanned in a defined and reproducible manner. Clavicle fractures healed in malposition can be simulated by osteotomy and fixation using a titanium/carbon external fixator. During image processing the first rib served as fixed reference in space. Clavicle, scapula and humerus were registered, segmented, and triangulated. The different positions were displayed as superimposed surface meshes and measurements performed automatically. Initial results of an intact shoulder girdle demonstrated that different arm positions including ante-/retroversion and abduction/elevation resulted solely in a transverse movement of the clavicle along/parallel to the first rib maintaining the periclavicular space. A radiolucent frame enabling systematic and reproducible CT scanning of upper torsos in various arm movements was developed and utilized to characterize the effect on the 3D volume of the periclavicular space. Initial results demonstrated exclusively transverse movement of the clavicle along/parallel to the first rib maintaining the periclavicular space during arm positions within a physiological range of motion

Introduction. Pedicle screw loosening in posterior instrumentation of thoracolumbar spine occurs up to 60% in osteoporotic patients. These complications may be alleviated using more flexible implant materials and novel designs that could be optimized with reliable computational modeling. This study aimed to develop and validate non-linear homogenized finite element (hFE) simulations to predict pedicle screw toggling. Method. Ten cadaveric vertebral bodies (L1-L5) from two female and three male elderly donors were scanned with high-resolution peripheral quantitative computed tomography (HR-pQCT, Scanco Medical) and instrumented with pedicle screws made of carbon fiber-reinforced polyether-etherketone (CF/PEEK). Sample-specific 3D-printed guides ensured standardized instrumentation, embedding, and loading procedures. The samples were biomechanically tested to failure in a toggling setup using an electrodynamic testing machine (Acumen, MTS) applying a quasi-static cyclic testing protocol of three ramps with exponentially increasing peak (1, 2 and 4 mm) and constant valley displacements. Implant-bone kinematics were assessed with a stereographic 3D motion tracking camera system (Aramis SRX, GOM). hFE models with non-linear, homogenized bone material properties including a strain-based damage criterion were developed based on intact HR-pQCT and instrumented 3D C-arm scans. The experimental loading conditions were imposed, the maximum load per cycle was calculated and compared to the experimental results. HR-pQCT-based bone volume fraction (BV/TV) around the screws was correlated with the experimental peak forces at each displacement level. Result. The nonlinear hFE models accurately (slope = 1.07, intercept = 0.2 N) and precisely (R. 2. = 0.84) predicted the experimental peak forces at each displacement level. BV/TV alone was a weak predictor (R. 2. <0.31). Conclusion. The hFE models enable fast design iterations aiming to reduce the risk of screw loosening in low-density vertebrae. Improved flexible implant designs are expected to contribute to reduced complication rates in osteoporotic patients

Abstract. OBJECTIVES. Staphylococcus aureus is one of the most common pathogens in orthopaedic biomaterial-associated infections. The transition of planktonic S. aureus to its biofilm phenotype is critical in the pathogenesis of biomaterial-associated infections and the development of antimicrobial tolerance, which leads to ineffective eradication in clinical practice. This study sought to elucidate the effect of non-lethal dispersion on antimicrobial tolerance in S. aureus biofilms. METHODS. Using a methicillin-sensitive S. aureus reference strain, the effect of non-lethal dispersion on gentamicin tolerance, cellular activity, and the intracellular metabolome of biofilm-associated bacteria were examined. Gentamicin tolerance was estimated using the dissolvable bead biofilm assay. Cellular activity was estimated using the triphenyltetrazolium chloride assay. Metabolome analysis was performed using tandem high-performance liquid chromatography and mass spectrometry. RESULTS. Non-lethal dispersion of biofilm-associated S. aureus was associated with a four-fold reduction in gentamicin tolerance and a 25% increase in cellular respiration of both dispersed and adherent cells. Metabolome analysis found non-lethal dispersion reduced intracellular levels of L-ornithine and L-proline, with increased levels of cyclic nucleotides (p<0.05) in both liberated cells and the remaining biofilm-associated bacteria. These metabolomic changes have previously been shown to be associated with inactivation of the carbon catabolite repression mechanism, which is a key regulatory gatekeeper in the cellular resuscitation of dormant S. aureus cells. CONCLUSION. The metabolomic pipeline described in this study presents a valuable tool in the elucidation of molecular mechanistic pathways in biofilm pathogenesis. Kreb's cycle reactivation, through the carbon catabolite repression regulatory mechanism, has been shown to be associated with the reversal of biofilm-associated gentamicin tolerance. Understanding of the biosynthetic changes associated with the biofilm state will assist in the discovery of novel therapeutic targets in the management of biomaterial-related infections. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction. Congenital scoliosis is a prevalent congenital spinal deformity, more frequently encountered than congenital lordosis or kyphosis. The prevailing belief is that most instances of congenital scoliosis are not hereditary but rather stem from issues in fetal spine development occurring between the 5th and 8th weeks of pregnancy. However, it has been linked to several genes in current literature. Our goal was to explore potential pathways through an exhaustive bioinformatics analysis of genes related to congenital scoliosis. Method. The literature from the 1970s to February 2024 was surveyed for genes associated with CS, and 63 genes were found to be associated with AIS out of 1743 results. These genes were analyzed using DAVID Bioinformatics. Result. Our pathway analysis has unveiled several significant associations with congenital scoliosis. Notably, “Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate” (P-Value:8.8E-3, Fold Enrichment: 20.6), “Central carbon metabolism in cancer” (P-Value:1.3E-3, Fold Enrichment: 10.3), and “Lysine degradation” (P-Value: 9.0E-3, Fold Enrichment: 9.1) emerge as statistically significant pathways. Additionally, “Endocrine resistance” (P-Value:4.4E-3, Fold Enrichment:7.4) and”EGFR tyrosine kinase inhibitor resistance” (P-Value: 1.7E-2, Fold Enrichment:7.3) pathways are noteworthy. These findings suggest a potential involvement of these pathways in the biological processes underlying congenital scoliosis. Furthermore, “Signaling pathways regulating pluripotency of stem cells” (P-Value:4.0E-4, Fold Enrichment:7.1), “Notch signaling pathway” (P-Value:6.7E-2, Fold Enrichment: 7.0), and “TGF-beta signaling pathway” (P-Value:6.2E-3, Fold Enrichment: 6.7) exhibit a less pronounced yet intriguing association that may warrant further investigation. Conclusion. In conclusion, our comprehensive analysis of the genetic etiology of congenital scoliosis has revealed significant associations with various pathways, shedding light on potential underlying biological mechanisms. While further research is needed to fully understand these associations and their implications, our findings provide a valuable starting point for future investigations into the management and treatment of congenital scoliosis

Menisci are crucial structures for knee homeostasis: they provide increase of congruence between the articular surfaces of the distal femur and tibial plateau, bear loading, shock absorption, lubrication, and proprioception. After a meniscal lesion, the golden rule, now, is to save as much meniscus as possible: only the meniscus tissue which is identified as unrepairable should be excised and meniscal sutures find more and more indications. Several different methods have been proposed to improve meniscal healing. They include very basic techniques, such as needling, abrasion, trephination and gluing, or more complex methods, such as synovial flaps, meniscal wrapping, or the application of fibrin clots. Basic research of meniscal substitutes has also become very active in the last decades. The features needed for a meniscal scaffold are: promotion of cell migration, it should be biomimetic and biocompatible, it should resist forces applied and transmitted by the knee, it should slowly biodegrade and should be easy to handle and implant. Several materials have been tested, that can be divided into synthetic and biological. The first have the advantage to be manufactured with the desired shapes and sizes and with precise porosity dimension and biomechanical characteristics. To date, the most common polymers are polylactic acid (PGA); poly-(L)-lactic acid (PLLA); poly- (lactic-co-glycolic acid) (PLGA); polyurethane (PU); polyester carbon and polycaprolactone (PCL). The possible complications, more common in synthetic than natural polymers are poor cell adhesion and the possibility of developing a foreign body reaction or aseptic inflammation, leading to alter the joint architecture and consequently to worsen the functional outcomes. The biological materials that have been used over time are the periosteal tissue, the perichondrium, the small intestine submucosa (SIS), acellular porcine meniscal tissue, bacterial cellulose. Although these have a very high biocompatibility, some components are not suitable for tissue engineering as their conformation and mechanical properties cannot be modified. Collagen or proteoglycans are excellent candidates for meniscal engineering, as they maintain a high biocompatibility, they allow for the modification of the porosity texture and size and the adaptation to the patient meniscus shape. On the other hand, they have poor biomechanical characteristics and a more rapid degradation rate, compared to others, which could interfere with the complete replacement by the host tissue. An interesting alternative is represented by hydrogel scaffolds. Their semi-liquid nature allows for the generation of scaffolds with very precise geometries obtained from diagnostic images (i.e. MRI). Promising results have been reported with alginate and polyvinyl alcohol (PVA). Furthermore, hydrogel scaffolds can be enriched with growth factors, platelet-rich plasma (PRP) and Bone Marrow Aspirate Concentrate (BMAC). In recent years, several researchers have developed meniscal scaffolds combining different biomaterials, to optimize the mechanical and biological characteristics of each polymer. For example, biological polymers such as chitosan, collagen and gelatin allow for excellent cellular interactions, on the contrary synthetic polymers guarantee better biomechanical properties and greater reliability in the degradation time. Three-dimensional (3D) printing is a very interesting method for meniscus repair because it allows for a patient-specific customization of the scaffolds. The optimal scaffold should be characterized by many biophysical and biochemical properties as well as bioactivity to ensure an ECM-like microenvironment for cell survival and differentiation and restoration of the anatomical and mechanical properties of the native meniscus. The new technological advances in recent years, such as 3D bioprinting and mesenchymal stem cells management will probably lead to an acceleration in the design, development, and validation of new and effective meniscal substitutes

In case of spine tumors, when en bloc vertebral column resection (VCR) is indicated and feasible, the segmental defect should be reconstructed in order to obtain an immediate stability and stimulate a solid fusion. The aim of this study is to share our experience on patients who underwent spinal tumor en bloc VCR and reconstruction consecutively. En bloc VCR and reconstruction was performed in 138 patients. Oncological and surgical staging were performed for all patients using Enneking and Weinstein-Boriani-Biagini systems accordingly. Following en bloc VCR of one or more vertebral bodies, a 360° reconstruction was made by applying posterior instrumentation and anterior implant insertion. Modular carbon fiber implants were applied in 111 patients, titanium mesh cage implants in 21 patients and titanium expandable cages in 3 patients; very recently in 3 cases we started to use custom made titanium implants. The latter were prepared according to preoperative planning of en bloc VCR based on CT-scan of the patient, using three dimensional printer. The use of modular carbon fiber implant has not leaded to any mechanical complications in the short and long term follow-up. In addition, due to radiolucent nature of this implant and less artifact production on CT and MRI, tumor relapse may be diagnosed and addressed earlier in compare with other implants, which has a paramount importance in these group of patients. We did not observe any implant failure using titanium cages. However, tumor relapse identification may be delayed due to metal artifacts on imaging modalities. Custom- made implants are economically more affordable and may be a good alternative choice for modular carbon fiber implants. The biocompatibility of the titanium make it a good choice for reconstruction of the defect when combined with bone graft allograft or autograft. Custom made cages theoretically can reproduce patients own biomechanics but should be studied with longer follow-up

As a part of the European Union BIOMED I study “Assessment of Bone Quality in Osteoporosis,” Sixty-nine second lumbar vertebral body specimens (L2) were obtained post mortem from 32 women and 37 men (age 24–92 years). Our initial remit was to study variations in density of the calcified tissues by quantitative backscattered electron imaging (BSE-SEM). To this end, the para-sagittal bone slices were embedded in PMMA and block surfaces micro-milled and carbon coated. Many samples were re-polished to remove the carbon coat and stained with iodine vapour to permit simultaneous BSE imaging of non-mineralised tissues - especially disc, annulus, cartilage and ligament - uncoated, at 50Pa chamber pressure. We have now studied most of these samples by 30-μm resolution high contrast resolution X-ray microtomography (XMT), typically 72 hours scanning time, thus giving exact correlation between high resolution BSE-SEM and XMT. The 3D XMT data sets were rendered using Drishti software to produce static and movie images for visualisation and edification. We have now selected a set of the female samples for reconstruction by 3D printing - taking as examples the youngest, post-menopausal, oldest, best, worst, and anterior and central compression fractures and anterior collapse with fusion to L3 - which will be attached to the poster display. The most porotic cases were also the most difficult to reconstruct. A surprising proportion of elderly samples showed excellent bone architecture, though with retention of fewer, but more massive, load-bearing trabeculae

Objectives. Ultraviolet (UV) light-mediated photofunctionalisation is known to improve osseointegration of pure titanium (Ti). However, histological examination of titanium alloy (Ti6Al4V), which is frequently applied in orthopaedic and dental surgery, has not yet been performed. This study examined the osseointegration of photofunctionalised Ti6Al4V implants. Methods. Ti and Ti6Al4V implants were treated with UV light, and the chemical composition and contact angle on the surfaces were evaluated to confirm photofunctionalisation. The implants were inserted into femurs in rats, and the rats were killed two or four weeks after the surgery. For histomorphometric analysis, both the bone–implant contact (BIC) ratio and the bone volume (BV) ratio were calculated from histological analysis and microcomputed tomography data. Results. The amount of carbon and the contact angle on both implants were significantly reduced after UV irradiation. The BIC ratios for both UV light-treated implants significantly increased at two weeks, but there was no significant difference at four weeks. There was no significant difference in the BV ratios between the UV light-treated and control implants at two or four weeks. Conclusions. This study suggests that photofunctionalisation of Ti6Al4V implants, similar to that of Ti implants, may promotes osseointegration in early but not in the late phase of osseointegration. Cite this article: R. Yamauchi, T. Itabashi, K. Wada, T. Tanaka, G. Kumagai, Y. Ishibashi. Photofunctionalised Ti6Al4V implants enhance early phase osseointegration. Bone Joint Res 2017;6:331–336. DOI: 10.1302/2046-3758.65.BJR-2016-0221.R1

The use of stem cells transplanted into the intervertebral disc (IVD) is a promising regenerative approach to treat intervertebral disc degeneration (IDD). The aim of this study was to assess the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) loaded with human mesenchymal stem cells (hMSCs), on IVD extracellular matrix synthesis and nucleus pulposus (NP) marker expression in a whole IVD culture model. HA was blended with batroxobin (BTX), a gelling agent activated in presence of PRP to construct a hydrogel. Bovine IVDs (n=25) were nucleotomised and filled with 1×10. 6. or 2×10. 6. hMSCs suspended in ∼150 mL of the PRP/HA/BTX hydrogel. IVDs harvested at day 0 and nucleotomised IVDs with no hMSCs and/or hydrogel were used as controls. hMSCs alone or encapsulated in the hydrogel were also cultured in well plates to examine the effect of the IVD microenvironment on hMSCs. After 1 week, tissue structure, scaffold integration and gene expression of anabolic (collagen type I, collagen type II and aggrecan), catabolic (matrix metalloproteinase 3 – MMP-3 –, MMP-13 and a disintegrin and metalloproteinase with thrombospondin motifs 4) and NP cell (cytokeratin 19, carbonic anhydrase 12, cluster of differentiation 24) markers were assessed. Histological analysis showed a good integration of the scaffold within the NP area with cell repopulation. At the gene expression level, the hMSC-loaded hydrogels demonstrated to increase disc cell anabolic and catabolic marker expression and promoted hMSC differentiation towards a NP cell phenotype. This study demonstrated that the HA/PRP/BTX may represent a valid carrier for hMSCs being capable of stimulating cell activity and NP marker expression as well as achieving a good integration with the surrounding tissues