SUMMARY. We report a prospective study of clinical data collected pre, intra and post operation to remove both cup and head components of 118 failed, current generation metal on metal (MOM) hips. Whilst component position was important, the majority were unexplained failures and of these the majority (63%) had cup inclination angles of less than 55 degrees. Poor biocompatibility of the wear debris may explain many of the failures. BACKGROUND. Morlock et al reported a retrospective analysis of 267 MOM hips but only 34 head and cup couples (ie most were femoral neck fractures) and without data necessary to define cause of failure. The commonest cause of failure in the National Joint Registry (NJR) is unexplained. METHODS. We categorised the cause of failure, as defined by the NJR, of all MOM hips received over an 18 month period that had a full set of pre, intra and post op data. A group of 40 patients with unilateral well functioning MOM hips was used for comparison. RESULTS. In the retrieval group, the median age was 61 years (25 to 87) and there were 80 females and 38 males. The median time between primary and revision operation was 35 months (4 to 121). Femoral head size was <50mm in 89 and >=50mm in 29. The causes of failure were: unexplained in 75; aseptic loosening (acetabular) in 12; aseptic loosening (femoral) in 7; dislocation/subluxation in 1; infection in 11; periprosthetic femoral fracture in 2; malalignment in 6; size mismatch in 3; other in 1. 47 (63%) of unexplained failures had cup inclination angles of less than 55 degrees. The unexplained failures had increased blood metal ions (p <0.0001) and cup inclination angle (p <0.005) but a decreased femoral head size (p <0.0001) when compared to well functioning MOM hip patients. CONCLUSION. The commonest cause of failed MOM hips was unexplained. Comparison to well functioning hips revealed that the mechanism may involve high blood metal ions but high cup inclination angle was not found in the majority of cases. Further biological and mechanical investigation into the underlying mechanism of failure is required

There are many methods for analysing wear volume in failed polyethylene acetabular components. We compared a radiological technique with three recognised ex vivo methods of measurement. We tested 18 ultra-high-molecular-weight polyethylene acetabular components revised for wear and aseptic loosening, of which 13 had pre-revision radiographs, from which the wear volume was calculated based upon the linear wear. We used a shadowgraph technique on silicone casts of all of the retrievals and a coordinate measuring method on the components directly. For these techniques, the wear vector was calculated for each component and the wear volume extrapolated using mathematical equations. The volumetric wear was also measured directly using a fluid-displacement method. The results of each technique were compared. The series had high wear volumes (mean 1385 mm. 3. ; 730 to 1850) and high wear rates (mean 205 mm. 3. /year; 92 to 363). There were wide variations in the measurements of wear volume between the radiological and the other techniques. Radiograph-derived wear volume correlated poorly with that of the fluid-displacement method, co-ordinate measuring method and shadowgraph methods, becoming less accurate as the wear increased. The mean overestimation in radiological wear volume was 47.7% of the fluid-displacement method wear volume. Fluid-displacement method, coordinate measuring method and shadowgraph determinations of wear volume were all better than that of the radiograph-derived linear measurements since they took into account the direction of wear. However, only radiological techniques can be used in vivo and remain useful for monitoring linear wear in the clinical setting. Interpretation of radiological measurements of acetabular wear must be done judiciously in the clinical setting. In vitro laboratory techniques, in particular the fluid-displacement method, remain the most accurate and reliable methods of assessing the wear of acetabular polyethylene

Abstract

Locking plates have led to important changes in bone fracture management, allowing flexible biological fracture fixation based on the principle of an internal fixator. The technique of locking plate fixation differs fundamentally from conventional plating and has its indications and limitations. Most of the typical locking plate failure patterns are related to basic technical errors, such as under-sizing of the implant, too short working length, and imperfect application of locking screws. After analysis of the fracture morphology and intrinsic stability following fracture reduction, a meticulous preoperative planning is mandatory under consideration of the principles of the internal fixator technique to avoid technical errors and inaccuracies leading to early implant failure.

Abstract. Objective. Short-stem total hip arthroplasty (THA) aims to preserve the proximal bone stock for future revisions, so that the first revision should resemble a primary intervention rather than a revision. This study aimed to compare the clinical and radiological outcomes in revision THA after failed short stem versus after failed conventional stem THA. Methods. This study included forty-five patients with revision THA divided into three groups (15 each); group A: revision after short stem, group B: revision after conventional cementless stem and group C revision after conventional cemented stem. The studied groups were compared regarding 31 variables including demographic data, details of the primary and revision procedures, postoperative radiological subsidence, hospital stay, time for full weight bearing (FWB), preoperative and postoperative clinical scores. Results. Early stem subsidence (40%) was the main indication of revision in group A compared to peri-prosthetic femoral fractures (PFFs) (73.3%) and aseptic loosening (53.3%) in group B and C respectively (P=0.021). The mean time to revision was significantly shorter in group A (15 months) compared to 95.33 and 189.40 months in group B and C respectively. (P=0.005). Sixty % (9 patients) in group A were revised in the first year. The mean operative time, blood loss, postoperative blood transfusion and hospital stay were significantly lower in group A compared to group B and C (P<0.001, <0.001, 0.002 and 0.001 respectively). Revisions in group A were performed using either short stems (13.3%) or conventional stems (86.7%) whilst 80% of patients needed long stems and 20% of patients needed conventional stems in group B and C (P<0.001). The mean postoperative Harris Hip Score (HHS) at the latest follow up was 87.07, 87.53 and 85.47 in group A, B and C respectively. All PFFS had excellent results according to Beal's and Tower's criteria; all fractures healed and the implants were stable. Conclusion. The most common cause of failure of short stems is early stem subsidence. Short stem THA has specific indications and patient selection is very crucial. Preoperative templating for short stems and a detailed analysis of the individual patient anatomy in anteroposterior and lateral views are mandatory to predict the correct implant size more accurately. The use of intraoperative imaging can verify the sizing, implant position, and sufficient contact with the lateral cortex. Revision of short stem THA resembled the primary THA. If a standard implant can be used in a surgical revision instead of a longer revision stem, this can be considered as an advantage for the hip arthroplasty treatment concept. However, this only applies if the longevity of the first treatment with a short stem is comparable with that of a standard stem. 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 and Objective. Osteochondral allograft (OCA) transplants have been used clinically for more than 40 years as a surgical option for joint restoration, particularly for young and active patients. While immediate graft rejection responses have not been documented, it is believed that the host's immunological responses may directly impact OCA viability, incorporation, integrity, and survival, and therefore, it is of the utmost importance to further optimize OCA transplantation outcomes. The influences of sub-rejection immune responses on OCA transplantation failures have not been fully elucidated therefore aimed to further characterize cellular features of OCA failures using immunohistochemistry (IHC) in our continued hopes for the successful optimization of this valuable surgical procedure. Materials and Methods. With IRB approval, osteochondral tissues that were resected from the knee, hip, and ankle of patients undergoing standard-of-care revision surgeries (N=23) to treat OCA failures and tissues from unused portions of OCAs (N=7) that would otherwise be discarded were recovered. Subjective histologic assessments were performed on hematoxylin and eosin-stained and toluidine blue-stained sections by a pathologist who was blinded to patient demographics, outcomes data, and tissue source. IHC for CD3, CD8, and CD20 were performed to further characterize the and allow for subjective assessment of relevant immune responses. Results. Eleven (48%) of the failed OCAs had aggregates of CD3+, CD8+, and CD20+ lymphocytes around small blood vessels in the bone marrow spaces and adipose/collagenous tissue of the allograft, while the non-implanted healthy control OCA tissues did not show any evidence of inflammation. The remaining failed OCAs (52%) did not show a similar pattern of T- and B-cell infiltrates around blood vessels. Other histologic abnormalities associated with failed OCAs included avascular necrosis, subchondral micro and macro fractures, subchondral collapse, bacterial infection, and/or articular cartilage erosion or delamination. Conclusions. The results from the present study support this possibility in that mixed aggregates of CD3+, CD8+, and CD20+ lymphocytes were observed around small blood vessels in approximately half of the failed OCAs. This potentially cytotoxic immune response may have contributed to the lack of functional survival of the OCA noted in these cases, and warrants further investigation as a possible failure mechanism that may be mitigated using post-transplantation management strategies

Introduction and Objective. Posterior and transforaminal lumbar interbody fusion (PLIF, TLIF) represent the most popular techniques in performing an interbody fusion amongst spine surgeons. Pseudarthrosis, cage migration, subsidence or infection can occur, with subsequent failed surgery, persistent pain and patient’ bad quality of life. The goal of revision fusion surgery is to correct any previous technical errors avoiding surgical complications. The most safe and effective way is to choose a naive approach to the disc. Therefore, the anterior approach represents a suitable technique as a salvage operation. The aim of this study is to underline the technical advantages of the anterior retroperitoneal approach as a salvage procedure in failed PLIF/TLIF analyzing a series of 32 consecutive patients. Materials and Methods. We performed a retrospective analysis of patients’ data in patients who underwent ALIF as a salvage procedure after failed PLIF/TLIF between April 2014 to December 2019. We recorded all peri-operative data. In all patients the index level was exposed with a minimally invasive anterior retroperitoneal approach. Results. Thirty-two patients (average age: 46.4 years, median age 46.5, ranging from 21 to 74 years hold- 16 male and 16 female) underwent salvage ALIF procedure after failed PLIF/TLIF were included in the study. A minimally invasive anterior retroperitoneal approach to the lumbar spine was performed in all patients. In 6 cases (18.7%) (2 infection and 4 pseudarthrosis after stand-alone IF) only anterior revision surgery was performed. A posterior approach was necessary in 26 cases (81.3%). In most of cases (26/32, 81%) the posterior instrumentation was overpowered by the anterior cage without a previous revision. Three (9%) intraoperative minor complications after anterior approach were recorded: 1 dural tear, 1 ALIF cage subsidence and 1 small peritoneal tear. None vascular injuries occurred. Most of patients (90.6%) experienced an improvement of their clinical condition and at the last follow-up no mechanical complication occurred. Conclusions. According to our results, we can suggest that a favourable clinical outcome can firstly depend from technical reasons an then from radiological results. The removal of the mobilized cage, the accurate endplate and disc space preparation and the cage implant eliminate the primary source of pain reducing significantly the axial pain, helping to realise an optimal bony surface for fusion and enhancing primary stability. The powerful disc distraction given by the anterior approach allows inserting large and lordotic cages improving the optimal segmental lordosis restoration

Abstract. Background. Tibiotalocalcaneal (TTC) fusion is indicated for severe arthritis, failed ankle arthroplasty, avascular necrosis of talus and as a salvage after failed ankle fixation. Patients in our study had complex deformities with 25 ankles having valgus deformities (range 50–8 degrees mean 27 degrees). 12 had varus deformities (range 50–10 degrees mean 26 degrees) 5 ankles an accurate measurement was not possible on retrospective images. 10 out of 42 procedures were done after failed previous surgeries and 8 out of 42 had talus AVN. Methods. Retrospective case series of patients with hindfoot nails performed in our centre identified using NHS codes. Total of 41 patients with 42 nails identified with mean age of 64 years. Time to union noted from X-rays and any complications noted from the follow-up letters. Patients contacted via telephone to complete MOXFQ and VAS scores and asked if they would recommend the procedure to patients suffering similar conditions. 17 patients unable to fill scores (5 deceased, 4 nails removed, 2 cognitive impairment and 6 uncontactable). Results. In our cohort 33/38 of hindfoot nails achieved both subtalar and ankle fusion in a mean time of 7 months. 25 patients with 26 nails had mean follow up with post op scores of 4 years. Their Mean MOXFQ scores were (Pain: 12.8 Walking: 12 Social: 8) and visual analogue pain score was 3. 85% of patients wound recommend this surgery for a similar condition. 20 complications with 15 requiring surgery(5 screw removals, 1 percutaneous drilling, 1 fusion site injection, 8 nail revisions). Conclusion. In our experience hindfoot nail TTC fusion reliably improves the function of patients with severe symptoms in a variety of pathophysiological conditions and complex deformities. Most of our patients would recommend this procedure. There is a lack of studies with long-term follow-up

Tendon injuries present a major clinical challenge, as they necessitate surgical intervention and are prone to fibrotic progression. Despite advances in physical therapy and surgical technique, tendons fail to return to full native functioning, underlining the need for a biological therapeutic to improve tendon healing. Myofibroblasts are activated fibroblasts that participate in the proliferative and remodeling phases of wound healing, and while these matrix-producing cells are essential for proper healing, they are also linked to fibrotic initiation. A subset of tenocytes has been shown to give rise to the myofibroblast fate, and potentially contribute to fibrotic tendon healing. A viable anti-fibrotic therapy in other tissues has been reprogramming the fibroblast-myofibroblast differentiation route, avoiding a more pro-fibrotic myofibroblast phenotype. Thus, defining the molecular programs that underlie both physiological and pathological tendon healing is critical for the development of potential pharmacologic treatments. Towards that end, we have taken advantage of spatial transcriptomics, using the tenocyte marker Scleraxis as a tool, and have outlined three major spatiotemporally distinct tenocyte differentiation trajectories (synthetic, proliferative, and reactive) following acute tendon injury in mouse FDL. We have further outlined key transcriptional controls that may be manipulated to alter the differentiation process and influence the resulting myofibroblast phenotype, thereby promoting regenerative tendon healing

Back pain is a leading cause of disability worldwide and it is primarily considered to be triggered by intervertebral disc (IVD) degeneration (IVDD). Current treatments may improve pain and mobility, but carry high costs and fail to address IVD repair or regeneration. As no effective therapeutic approach has been proposed to restore inflamed and degenerated IVDs, there is the urgent need to clarify the key pathomechanism of IVDD, the involvement of inflammation, particularly complement activation in matrix catabolism, and how to target them towards tissue repair/regeneration. Mesenchymal stem cell (MSC)-based therapies have become the focus of several regenerative IVD studies. Although patients in clinical trials reported less pain after cell therapy, the long-term success of cell engraftment is unclear due to the hostile IVD environment. The mechanism-of-action of MSCs is mostly dependent on the secreted soluble factors. Moreover, priming of MSC with interleukin (IL)-1β modulates the secretome content, improving its anti-inflammatory and regenerative effect on IVDD organ culture models. MSC-derived extracellular vesicles (EVs) have also been shown to modulate human IVD cells towards a healthy IVD phenotype in vitro. However, the mechanisms involved in the effect of secretome and EVs, particularly with regard to immunomodulation and matrix metabolism, are not fully understood. Our work investigates the effects of secretome and EVs secreted by IL-1β-primed MSCs to impair IVD matrix degradation and/or improve matrix formation in IVDD

Intervertebral disc degeneration can lead to physical disability and significant pain, while the present therapeutics still fail to biochemically and biomechanically restore the tissue. Stem cell-based therapy in treating intervertebral disc (IVD) degeneration is promising while transplanting cells alone might not be adequate for effective regeneration. Recently, gene modification and 3D-printing strategies represent promising strategies to enhanced therapeutic efficacy of MSC therapy. In this regard, we hypothesized that the combination of thermosensitive chitosan hydrogel and adipose derived stem cells (ADSCs) engineered with modRNA encoding Interleukin − 4 (IL-4) can inhibit inflammation and promote the regeneration of the degenerative IVD. Rat ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IL-4 modRNA engineered ADSCs (named as IL-4-ADSCs) on nucleus pulposus cells. ModRNA transfected mouse ADSCs with high efficiency and the IL-4 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IL-4 protein. In vitro, IL-4-ADSCs induced increased anabolic markers expression of nucleus pulposus cells in inflammation environment compared to untreated ADSCs. These findings collectively supported the therapeutic potential of the combination of thermosensitive chitosan hydrogel and IL-4-ADSCs for intervertebral disc degeneration management. Histological and in vivo validation are now being conducted

Primary implant stability is critical for osseointegration and subsequent implant success. Small displacements on the screw/bone interface are necessary for implant success, however, larger displacements can propagate cracks and break anchorage points which causes the screw to fail. Limited information is available on the progressive degradation of stability of an implanted bone screw since most published research is based on monotonic, quasi-static loading [1]. This study aims to address this gap in knowledge. A total of 100 implanted trabecular screws were tested using multi-axial loading test set-up. Screws were loaded in cycles with the applied force increasing 1N in each load cycle. In every load cycle, Peak forces, displacements, and stiffness degradation (calculated in the unloading half of the cycle) where recorded. 10 different loading configurations where tested. The damage vs displacement shows a total displacement at the point of failure between 0.3 and 0.4 mm while an initial stiffness reduction close to 40%. It is also shown that at a displacement of ~0.1 mm, the initial stiffness of every sample had degraded by 20% (or more) meaning that half of the allowable degradation occurred in the first 25-30% of the total displacement. Other studies on screw overloading [1] suggests similar results to our concerning initial stiffness degradation at the end of the loading cycle. Our results also show that the initial stiffness degrades faster with relatively small deformations suggesting that the failure point of an implanted screw might occur before the common failure definition (pull-out force, for example). These results are of great significance since primary implant stability is better explained by the stiffness of the construct than by its failure point

Total hip replacement (THR) is indicated for patients with osteoarthritis where conservative treatment has failed. Metal alloys used in THR implants such as cobalt-chromium (CoCr) have been known to cause pro-inflammatory reactions in patients, therefore leading to the need for costly revision surgery. This study therefore aimed to investigate the role of TLR4 in the activation of a human osteoblast model in response to CoCr particles in vitro. Human osteoblasts (MG-63 cell line) were seeded at a density of 100,000 cells and treated with 0.5, 5, 50mm3 CoCr particles per cell for 24-hours. Trypan blue and the XTT Cell Proliferation Kit II were then used in conjunction with the cells to assess CoCr-induced cytotoxicity. Cells were pre-treated with a commercially available TLR4-specific small molecule inhibitor (CLI-095) for 6 hours. Untreated cells were used as a negative control and lipopolysaccharide (LPS) was used as a positive control. Following treatment the cell supernatant was collected and used for enzyme-linked immunosorbant assay (ELISA) to measure the secretion of interleukin-8 (IL-8), CXCL10, and interleukin-6 (IL-6). Trypan blue and XTT analysis showed that there was no significant changes to cell viability or proliferation at any dose used of CoCr after 24 hours. There was a significant increase in protein secretion of IL-8 (p<0.001), CXCL10 (p<0.001), and IL-6 (p<0.001) in the cells which received the highest dosage of CoCr. This pro-inflammatory secretory response was ameliorated by TLR4 blockade (p<0.001). CoCr particles are not cytotoxic to osteoblasts but they do induce pro-inflammatory changes as characterised by increased secretion of chemokines IL-8, CXCL10, and IL-6. These responses occur via a TLR4-mediated pathway and upon inhibition they can be effectively ameliorated. This is particularly important as TLR4 could be a potential target for pharmacological intervention used in patients experiencing immunological reactions to metal implant debris

A comprehensive understanding of the self-repair abilities of menisci and their overall function in the knee joint requires three-dimensional information. However, previous investigations of the meniscal blood supply have been limited to two-dimensional imaging methods, which fail to accurately capture tissue complexity. In this study, micro-CT was used to analyse the 3D microvascular structure of the meniscus, providing a detailed visualization and precise quantification of the vascular network. A contrast agent (μAngiofil®) was injected directly into the femoral artery of cadaver legs to provide the proper contrast enhancement. First, the entire knee joint was analysed with micro-CT, then to increase the applicable resolution the lateral and medial menisci were excised and investigated with a maximum resolution of up to 4 μm. The resulting micro-CT datasets were analysed both qualitatively and quantitatively. Key parameters of the vascular network, such as vascular volume fraction, vessel radius, vessel length density, and tortuosity, were separately determined for the lateral and medial meniscus, and their four circumferential zones defined by Cooper. In accordance with previous literature, the quantitative micro-CT data confirm a decrease in vascular volume fraction along the meniscal zones. The highest concentration of blood vessels was measured in the meniscocapsular region 0, which is characterized by vascular segments with a significantly larger average radius. Furthermore, the highest vessel length density observed in zone 0 suggests a more rapid delivery of oxygen and nutrients compared to other regions. Vascular tortuosity was detected in all circumferential regions, indicating the occurrence of vascular remodelling in all tissue areas. In conclusion, micro-CT is a non-invasive imaging technique that allows for the visualization of the internal structure of an object in three dimensions. These advanced 3D vascular analyses have the potential to establish new surgical approaches that rely on the healing potential of specific areas of the meniscus. Acknowledgements: The authors acknowledge R. Hlushchuk, S. Halm, and O. Khoma from the University of Bern for their help with contrast agent perfusions

Introduction. Distal triceps tendon rupture is related to high complication rates with up to 25% failures. Elbow stiffness is another severe complication, as the traditional approach considers prolonged immobilization to ensure tendon healing. Recently a dynamic high-strength suture tape was designed, implementing a silicone-infused core for braid shortening and preventing repair elongation during mobilization, thus maintaining constant tissue approximation. The aim of this study was to biomechanically compare the novel dynamic tape versus a conventional high-strength suture tape in a human cadaveric distal triceps tendon rupture repair model. Method. Sixteen paired arms from eight donors were used. Distal triceps tendon rupture tenotomies and repairs were performed via the crossed transosseous locking Krackow stitch technique for anatomic footprint repair using either conventional suture tape (ST) or novel dynamic tape (DT). A postoperative protocol mimicking intense early rehabilitation was simulated, by a 9-day, 300-cycle daily mobilization under 120N pulling force followed by a final destructive test. Result. Significant differences were identified between the groups regarding the temporal progression of the displacement in the distal, intermediate, and proximal tendon aspects, p<0.001. DT demonstrated significantly less displacement compared to ST (4.6±1.2mm versus 7.8±2.1mm) and higher load to failure (637±113N versus 341±230N), p≤0.037. DT retracted 0.95±1.95mm after each 24-hour rest period and withstood the whole cyclic loading sequence without failure. In contrast, ST failed early in three specimens. Conclusion. From a biomechanical perspective, DT revealed lower tendon displacement and greater resistance in load to failure over ST during simulated daily mobilization, suggesting its potential for earlier elbow mobilization and prevention of postoperative elbow stiffness

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 10. 7. 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

Wear debris from implant interfaces is the major factor leading to periprosthetic osteolysis. Fibroblast-like synoviocytes (FLSs) populate the intimal lining of the synovium and are in direct contact with wear debris. This study aimed to elucidate the effect of Ti particles as wear debris on human FLSs and the mechanism by which they might participate in the bone remodeling process during periprosthetic osteolysis. FLSs were isolated from synovial tissue from patients, and the condition medium (CM) was collected after treating FLSs with sterilized Ti particles. The effect of CM was analyzed for the induction of osteoclastogenesis or any effect on osteogenesis and signaling pathways. The results demonstrated that Ti particles could induce activation of the NFκB signaling pathway and induction of COX-2 and inflammatory cytokines in FLSs. The amount of RANL in the conditioned medium collected from Ti particle-stimulated FLSs (Ti CM) showed the ability to stimulate osteoclast formation. The Ti CM also suppressed the osteogenic initial and terminal differentiation markers for osteoprogenitors, such as alkaline phosphate activity, matrix mineralization, collagen synthesis, and expression levels of Osterix, Runx2, collagen 1α, and bone sialoprotein. Inhibition of the WNT and BMP signaling pathways was observed in osteoprogenitors after the treatment with the Ti CM. In the presence of the Ti CM, exogenous stimulation by WNT and BMP signaling pathways failed to stimulate osteogenic activity in osteoprogenitors. Induced expression of sclerostin (SOST: an antagonist of WNT and BMP signaling) in Ti particletreated FLSs and secretion of SOST in the Ti CM were detected. Neutralization of SOST in the Ti CM partially restored the suppressed WNT and BMP signaling activity as well as the osteogenic activity in osteoprogenitors. Our results reveal that wear debris-stimulated FLSs might affect bone loss by not only stimulating osteoclastogenesis but also suppressing the bone-forming ability of osteoprogenitors. In the clinical setting, targeting FLSs for the secretion of antagonists like SOST might be a novel therapeutic approach for preventing bone loss during inflammatory osteolysis

Intervertebral disc (IVD) degeneration is the most frequent cause of Low Back Pain (LBP) affecting nearly 80% of the population [1]. Current treatments fail to restore a functional IVD or to provide a long-term solution, so, there is an urgent need for novel therapeutic strategies. We have defined the IVD extracellular matrix (ECM) profile, showing that the pro-regenerative molecules Collagen type XII and XIV, are uniquely expressed during fetal stages [2]. Now we propose the first fetal injectable biomaterial to regenerate the IVD. Fetal decellularized IVD scaffolds were recellularized with adult IVD cells and further implanted in vivo to evaluate their anti-angiogenic potential. Young decellularized IVD scaffolds were used as controls. Finally, a large scale protocol to produce a stable, biocompatible and easily injectable fetal IVD-based hydrogel was developed. Fetal scaffolds were more effective at promoting Aggrecan and Collagen type II expression by IVD cells. In a Chorioallantoid membrane assay, only fetal matrices showed an anti-angiogenic potential. The same was observed in vivo when the angiogenesis was induced by human NP cells. In this context, human NP cells were more effective in GAG synthesis within a fetal microenvironment. Vaccum-assisted perfusion decellularized IVDs were obtained, with high DNA removal and sGAG retention. Hydrogel pre-solution passed through 21-30G needles. IVD cells seeded on the hydrogels initially decreased metabolic activity, but increased up to 70% at day 7, while LDH assay revealed cytotoxicity always below 30%. This study will open new avenues for the establishment of a disruptive treatment for IVD degeneration with a positive impact on the angiogenesis associated with LBP, and on the improvement of patients’ quality of life. Acknowledgements: Financial support was obtained from EUROSPINE, ON Foundation and FCT (Fundação para a Ciência e a Tecnologia)

Chronic low back pain (CLBP) is the most common cause of disability worldwide, and lumbar spine fusion (LSF) is often chosen to treat pain caused by advanced degenerative disease when clinical treatment failed certain cases, the post-surgical outcomes are not what was expected. Several studies highlight how important are. In psychological variables during the postoperative spine surgery period. The aim of this study is to assess the role of preoperative depression on postoperative clinical outcomes. We included patients who underwent LSF since December 2021. Preoperative depression was assessed administering Beck Depression Inventory questionnaire (BDI). And pain and disability were evaluated at 1, 3, and 6 months, administering respectively Visual Analogic Scale (VAS) and Oswestry Disability Index (ODI). As statistical analysis Mann-Whitney test was performed. We included 46 patients, 20 female (43,5%) and 26 male (56,5%) with an average age of 64,2. The population was divided in two groups, fixing the BDI cut-off point at 10. Patients with BDI < 10 points (N=28) had normal mental health status, instead patients with BDI > 10 points (N=16) had depressive disorders. At 3 months patients with healthy mental status reported statistically significant reduction of pain (U = 372,5, p = .006) and improvement of disability but without statistical significancy (U = 318, p = 0,137). At 6 months patients without psychological disease reported statistically significant reduction of pain (U = 342, p = 0,039) and disability (U = 372,5, p = 0,006). This study demonstrates the correlation between pre-existing depressive state and poorer clinical outcomes after spine surgery. These results are consistent with the literature. Therefore, during the surgical decision making it is crucial to take psychological variables into account in order to predict the results after surgery and inform patients on the potential influence of mental status

Introduction. When designing a new osteosynthesis device, the biomechanical competence must be evaluated with respect to the acting loads. In a previous study, the loads on the proximal phalanx during rehabilitation exercises were calculated. This study aimed to assess the safety of a novel customizable osteosynthesis device compared to those loads to determine when failure would occur. Method. Forty proximal phalanges were dissected from skeletally mature female sheep and divided into four testing groups. A custom 3D printed cutting and drilling guide was used to create a reduced osteotomy and pilot holes to insert four 1.5 mm cortical screws. A novel light-curable polymer composite was used to fixate the bones with an in situ fixation patch. The constructs were tested in cyclic four-point bending in a bioreactor with ringer solution at 37°C with a valley load of 2 N. Four groups (N = 10) had increasing peak loads based on varying safety factors relative to the physiological loading (G1:100x, G2:150x, G3:175x, G4:250x). Each specimen was tested for 12,600 cycles (6 weeks of rehabilitation) or until failure occurred. After the test the thickness of the patch was measured with digital calipers and data analysis was performed in Python and R. Result. All samples survived in G1, and all failed in G4. G2 and G3 had 1 and 8 failures, respectively. There was no significant difference in patch thickness in all survivor samples against failures (p = 0.131), however, there was a significant difference in the displacement amplitude in the final cycle (0.072 mm vs. 0.15 mm; p < 0.001). Conclusion. This study found the survival and failure limits of a novel osteosynthesis device as a function of physiological loading. These results indicate that such fixations could withstand 100x the loading for typical non-weightbearing rehabilitation. Further studies are needed to confirm the safety for other conditions