Objectives. We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods. We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results. The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p < 0.05, one-way analysis of variance). The probabilities of a surgeon obtaining a 10 mm surgical margin with a 3 mm tolerance were 90.2% in AR-assisted resections, and 70.7% in conventional resections. Conclusion. We demonstrated that the accuracy of tumour resection was satisfactory with the help of the AR navigation system, with the tumour shown as a virtual template. In addition, this concept made the navigation system simple and available without additional cost or time. Cite this article: H. S. Cho, Y. K. Park, S. Gupta, C. Yoon, I. Han, H-S. Kim, H. Choi, J. Hong. Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143

Introduction. Vascularized fibular grafting following tumor resection is an essential treatment option in limb salvage surgery. This study aimed to assess the surgical and oncological outcomes of patients treated in Denmark between 2010 and 2022. Method. We present a retrospective review of a national cohort comprising 27 patients. The indications were 13 cases of Ewing sarcoma, 12 cases of osteosarcoma, and 2 cases of giant cell tumor. The median age at surgery was 16 years (range: 2-39), and the median follow-up was 82 months (range: 12-138). Patients were analyzed overall and stratified into upper and lower extremity groups based on tumor location. Result. The primary rate of graft union was 63%, and after secondary procedures, the overall rate of graft union was 67%, with a median time to union of 13 months (range: 7-29). The reoperation rate was 74%, while the rate of limb salvage was 93%, with two patients undergoing amputation during follow-up. The 5-year overall survival rate was 81% (95% CI: 61-92). Patients with upper extremity tumors were more likely to attain graft union (92% vs. 47%, p=0.02) and less likely to undergo multiple reoperations (17% vs 60%, p=0.047) compared to patients with lower extremity tumors. Conclusion. Vascularized fibula grafting remains a valuable option in limb salvage surgery with acceptable long-term outcomes. However, especially in lower extremity cases, a low rate of graft union and multiple reoperations are to be expected

Despite considerable legacy issues, Girdlestone's Resection Arthroplasty (GRA) remains a valuable tool in the armoury of the arthroplasty surgeon. When reserved for massive lysis in the context of extensive medical comorbidities which preclude staged or significant surgical interventions, and / or the presence of pelvic discontinuity, GRA as a salvage procedure can have satisfactory outcomes. These outcomes include infection control, pain control and post-op function. We describe a case series of 13 cases of GRA and comment of the indications, peri, and post-operative outcomes. We reviewed all cases of GRA performed in our unit during an 8 year period, reviewing the demographics, indications, and information pertaining to previous surgeries, and post op outcome for each. Satisfaction was based on a binary summation (happy/unhappy) of the patients’ sentiments at the post-operative outpatient consultations. 13 cases were reviewed. They had a mean age of 75. The most common indication was PJI, with 10 cases having this indication. The other three cases were performed for avascular necrosis, pelvic osteonecrosis secondary to radiation therapy and end stage arthritis on a background of profound learning disability in a non-ambulatory patient. The average number of previous operations was 5 (1-10). All 13 patients were still alive post girdlestone. 7 (54%) were satisfied, 6 were not. 3 patients were diabetic. 5 patients developed a sinus tract following surgery. With sufficient pre-op patient education, early intensive physiotherapy, and timely orthotic input, we feel this procedure remains an important and underrated and even compassionate option in the context of massive lysis and / or the presence of pelvic discontinuity / refractory PJI. GRA should be considered not a marker of failure but as a definitive procedure that gives predictability to patients and surgeon in challenging situations

Background. In certain clinical situations, complex local anatomy and limitations of surgical exposure can make adequate and bone tumor ablation, resection and reconstruction very challenging. We wished to review our clinical experience and accuracy achieved with entirely virtually planned single stage tumor ablation/resection and reconstructions. Methods. We report 6 cases of bone tumors in which tumor removal (by radio-frequency (RF) ablation and/or resection) and subsequent reconstruction were based entirely on pre-operative virtual analysis and planning. All interventions were accomplished with specifically designed and pre-operatively manufactured 3D-printed drill & resection guides. Immediate subsequent defect reconstruction was either performed with a precisely matching allograft (n=1) or composite metal implant (n=5) consisting of a defect specific titanium scaffold and multiple integrated fixation features to provide optimal immediate stability as well as subsequent opportunity for osseointegration. We reviewed the sequence of all procedural steps as well as the accuracy of each saw blade or drill trajectory by direct intra-operative measurement, post-operative margin status and virtual comparison of pre- and post-operative CT scans. Results. Intra-operative application/assembly of the resection guides could be accomplished with relative ease in all cases, permitting quick and efficient reproduction of the planned osteotomies as well as RF-probe trajectories with a high degree of accuracy. Histologically all resection margins were negative as planned except in one case where one pelvic resection was extended due to intraoperative concern of possible local tumor progression. All implants could be placed as planned, with post-operative imaging demonstrating satisfactory implant position. Virtual analysis of post-operative CT scans confirmeded minimal deviation of final implant position from the pre-operative plan. Conclusion. Reliable, accurate placement of tumor biopsy/ablation tracts and resection planes and their optimal alignment with respect to critical structures, tumor extent and desired preservation of unaffected bone is the most challenging and time consuming step during the analysis and planning phase. However it is also the crucial step with regard to subsequent design and production of clinically and oncologically meaningful case-specific drill/resection guides and implants. If these prerequisites are met, computer assisted virtual planning along with 3Dprinting-technology can afford high intraoperative accuracy, contribute to increased intra-operative surgeon confidence and decreased operative time

The aim of this study was to evaluate the time of return to play of elite basketball and voleyball players (both grouped together as jumper) with Haglund deformity after surgical resection of the prominence in the postero-superolateral aspect of the calcaneum. Haglund deformity is a prominence in the postero superolateral aspect of the calcaneum, causing a painful bursitis, which may be difficult to treat by non-operative techniques. In this study, we evaluated the duration that is needed to reach a level that a player perform regularly in a competition. This study consists of players operated by the same surgeon with same technique from 2011 to 2019. Twenty eight feet of 22 patients underwent resection of Haglund deformity with lateral approach and the outcome was analysed using AOFAS Ankle-Hind Foot Scale for hindfoot and time to restart a full range regular training was reported. All players received one dose (5–6 cc) platelet rich fibrin to attachement site of Achilles tendon peroperatively just after decompression of prominence. The mean AOFAS score at the follow up was 90/100, at the end of first year and the majority of players returned to play at 4th to 8th month of follow-up. Only two players with deformity of three feet could start to perform after one year. We conclude that minimal invasive approach ostectomy is an effective treatment for players suffering from Haglund deformity and the results were from good to excellent. However, the player should be well informed that the recovery and returning to play can take a longer time than they expect

The routine use of a fixed distal femoral resection angle in total knee arthroplasty (TKA) assumes little or no variation in the angle between the anatomical and mechanical femoral axes (FMA angle) in different patients. The aims of this study were threefold, firstly to investigate the distribution of FMA angle in TKA patients, secondly to identify any correlation between the FMA angle and the pre-operative coronal mechanical femoro-tibial (MFT) angle and in addition to assess post-operative MFT angle with fixed or variable distal femoral resection angles. 277 primary TKAs were performed using either fixed or variable distal femoral resection angles (174 and 103 TKAs respectively), with intramedullary femoral and extramedullary tibial jigs. The variable distal femoral resection angles were equal to the FMA angle measured on pre-operative Hip-Knee-Ankle (HKA) digital radiographs for each patient. Outcomes were assessed by measuring the FMA angle and the pre- and post-operative MFT angles on HKA radiographs. The FMA angle ranged from 2° to 9° (mean 5.9°). Both cohorts showed a correlation between FMA and pre-operative MFT angles (fixed: r = -0.499, variable: r = -0.346) with valgus knees having lower FMA angles. Post-operative coronal alignment within ±5° increased from 86% in the fixed angle group to 96% when using a variable angle, p = 0.025. For post-operative limb alignment within ±3°, accuracy improved from 67% (fixed) to 85% (variable), p = 0.002. These results show that the use of a fixed distal femoral resection angle is a source of error regarding post-operative coronal limb malalignment. The correlation between the FMA angle and pre-operative varus-valgus alignment supports the rational of recommending the adjustment of the resection angle according to the pre-operative deformity (3°-5° for valgus, 6°-8° for varus) in cases where HKA radiographs are not available for pre-operative planning

Background. Surgical resection of middle facet tarsal coalition is a well documented treatment option in symptomatic individuals that do not respond to conservative treatment. The ability to return to full recreational activity post resection may have implications on foot biomechanics and possibly degenerative changes in the subtalar and adjacent joints. Hypothesis. Open resection of middle facet tarsal coalitions should improve subtalar joint motion and biomechanical function and facilitate return to sports. Aim. The aim of this study was to assess the outcomes of open resection of middle facet tarsal coalitions (MFTCs) with particular emphasis on return to sports. Methods. Retrospective review of clinical and radiographic records of paediatric and adolescent patients who had open resection of middle facet tarsal coalitions. The ankle and hind foot were evaluated according to the American Orthopaedic Foot and Ankle Society Ankle-Hind foot Scale (AOFAS). We also quantified the return-to-activity time after tarsal coalition surgery. Results. We identified thirteen patients (Mean age; 13.7years Range; 7–21 years) with eighteen middle facet tarsal coalitions operated over a seven year period. Ten patients (12 feet) who underwent resection had an average return to recreational activity time of approximately twelve weeks and reported better exercise tolerance post resection. Conclusion. Surgical excision of middle facet tarsal coalitions has a favourable outcome with respect to return to sports

Introduction and Objective. Zone 2 flexor tendon injuries are still one of the challenges for hand surgeons. It is not always possible to achieve perfect results in hand functions after these injuries. There is no consensus in the literature regarding the treatment of zone 2 flexor tendon injuries, tendon repair and surgical technique to be applied to the A2 pulley. The narrow fibro-osseous canal structure in zone 2 can cause adhesions and loss of motion due to the increase in tendon volume due to surgical repair. Different surgical techniques have been defined to prevent this situation. In our study, in the treatment of zone 2 flexor tendon injuries; Among the surgical techniques to be performed in addition to FDP tendon repair; We aimed to compare the biomechanical results of single FDS slip repair, A2 pulley release and two different pulley plasty methods (Kapandji and V-Y pulley plasty). Materials and Methods. In our study, 12 human upper extremity cadavers preserved with modified Larssen solution (MLS) and amputated at the mid ½ level of the arm were used. A total of 36 fingers (second, third and the fourth fingers were used for each cadaver) were divided into four groups and 9 fingers were used for each group. With the finger fully flexed, the FDS and FDP tendons were cut right in the middle of the A2 pulley and repaired with the cruciate four-strand technique. The surgical techniques described above were applied to the groups. Photographs of fingers with different loads (50 – 700 gr) were taken before and after the application. Proximal interphalangeal (PIP) joint angle, PIP joint maximum flexion angle and bowstring distance were measured. The gliding coefficient was calculated by applying the PIP joint angle to the single-phase exponential association equation. Results. Gliding coefficient after repair increased by %21.46 ± 44.41, %62.71 ± 116.9, %26.8 ± 35.35 and %20.39 ± 28.78 in single FDS slip repair, A2 pulley release, V-Y pulley plasty and Kapandji plasty respectively. The gliding coefficient increased significantly in all groups after surgical applications (p<0.05). PIP joint maximum flexion angle decreased by %3.17 ± 7.92, %12.82 ± 10.94, %8.33 ± 3.29 and %7.35 ± 5.02 in single FDS slip repair, A2 pulley release, V-Y pulley plasty and Kapandji plasty respectively. PIP joint maximum flexion angle decreased significantly after surgery in all groups (p<0.05). However, there was no statistically significant difference between surgical techniques for gliding coefficient and PIP joint maximum flexion angle. Bowstring distance between single FDS slip repair, kapandji pulley plasty and V-Y pulley plasty showed no significant difference in most loads (p>0.05). Bowstring distance was significantly increased in the A2 pulley release group compared to the other three groups (p<0.05). Conclusion. Digital motion was negatively affected after flexor tendon repair. Similar results were found in terms of gliding coefficient and maximum flexion angle among different surgical methods. As single FDS slipe repair preserves the anatomical structure of the A2 pulley therefore we prefer it as an ideal method for zone 2 flexor tendon repair. However, resection of FDS slip may jeopardizes nutrition to the flexor digitorum profundus tendon which weakens the repair site. Therefore the results must be confirmed by an in vivo study before a clinical recommendation can be made. Keywords: Flexor tendon; injury; pulley plasty; cadaver;

Summary. This study describes the use of a quasi-static, 6DOF knee loading simulator using cadaveric specimens. Muscle force profiles yield repeatable results. Intra-articular pressure and contact area are dependent on loading condition and ACL integrity. Introduction. Abnormal contact mechanics of the tibiofemoral joint is believed to influence the development and progression of joint derangements. As such, understanding the factors that regulate joint stability may provide insight into the underlying injury mechanisms. Muscle action is believed to be the most important factor since it is the only dynamic regulator of joint stability. Furthermore, abnormal muscle control has been experimentally linked to the development of OA [Herzog, 2007] and in vivo ACL strain [Fleming, 2001]. However, the individual contributions to knee joint contact mechanics remain unclear. Thus, the purpose of this study was to examine the effects of individual muscle contributions on the tibiofemoral contact mechanics using an in-vitro experimental protocol. Methodology. Contact mechanics of 6 fresh frozen cadaver knee specimens were evaluated using the UofO Oxford knee loading device. Various combinations of quadriceps-hamstring co-contraction ratios were applied to the knee while it was “suspended” between the hip and foot components of the device. Loads of six muscle groups were computed using a hill-type musculoskeletal model [Buchanan, 2004]. Simulated ground reaction forces were also applied to the knee to represent force profiles of weight acceptance during gait as it has been shown to produce peak knee joint force in the gait cycle [Shelburne et al., 2006]. For respective medial and lateral joint compartments, the mean contact area (MC-CA and LC-CA), mean contact pressure (MC-CP and LC-CP), peak pressure (MC-PP and LC-PP), and centre of force displacement (MC-COFD and LC-COFD) were determined using a 4011 piezoelectric sensor form Tekscan (Tekscan Inc. Boston, MA). Additionally, the ACL was resected and measurements were repeated. Pearson correlations (r) examined the reliability of measurements as well as the effect an ACL transection on articular loads. Results. Positive correlations were computed for the following: COFD with intact ACL (r=0.99), COFD with resected ACL (r=0.82), MC-COFD pre vs. post ACL- resection (0.91). Furthermore, preliminary results indicated a positive correlation between MC-CA and ACL integrity (r=0.97). Discussion. The repeatability of the measured dependant variables validates the use of the knee-loading device. Interestingly, contact mechanics are more variable post ACL resection for a given muscle loading condition, indicating a decrease in knee joint stability. Also, the COFD is dependent on the different ratios of muscle loads applied to the knee, which demonstrates the importance of muscle action to the modulation of contact forces

Distal femur resection for correction of flexion contractures in total knee arthroplasty (TKA) can lead to joint line elevation, abnormal knee kinematics and patellofemoral problems. The aim of this retrospective study was to establish the contribution of soft tissue releases and bony cuts in the change in maximum knee extension in TKA. Data were available for 211 TKAs performed by a single surgeon using a medial approach. Intra-operatively pre- and post-implant extension angles and the size of bone resection were collected using a commercial navigation system. The thickness of polyethylene insert and the extent of soft tissue release performed (no release, moderate and extensive release) were collected from the patient record. A linear model was used to predict change in maximum extension from pre- to post-implant. The analysis showed that bone cuts (p<0.001), soft tissue release (p=0.001) and insert thickness (p=0.010) were all significant terms in the model (r. 2. adj. =0.170). This model predicted that carrying out a TKA with 19 mm bone cuts, 10 mm insert and no soft tissue release would give 4.2° increase in extension. It predicted that a moderate release would give a further 2.8° increase in extension with an extensive release giving 3.9°. For each mm increase in bone cuts the model predicted an 0.8° increase in extension and for each mm increase in insert size a decrease extension by 1.1°. The modelling results show that in general to increase maximum extension by the same as an extensive soft tissue release that bone cuts would have to be increased by 4–5 mm. However this model only accounted for 17% of the variation in change in extension pre- to post-implant so may not be accurate at predicting outcomes for specific patients

Chordoma of the cervical spine is a rare but life-threatening disease with a relentless tendency towards local recurrence. Wide en bloc resection is recommended, but it is frequently not feasible in the cervical spine. Radiation therapy including high-energy particle therapy is commonly used as adjuvant therapy. The goal of this study was to examine treatment and outcome of patients with chordoma of the cervical spine. Patients affected by cervical spine chordoma who underwent surgery at the Rizzoli Institute and University Hospital of Modena, between 2007 and 2021 were identified. The clinical, pathologic, and radiographic data were reviewed in all cases. Patient outcomes including local recurrence and disease-specific survival (DSS) were analyzed using chi-square test and Kaplan-Meier survival analysis. Characteristics of the 29 patients (10 females; 19 males) included: median age at surgery 52.0 years (IQR 35.5 - 62.5 years), 10 (35%) involved upper cervical spine, 16 (55%) with tumors in the mid cervical spine, and 4 in the lower cervical spine (10%). Median tumor volume was 16 cm. 3. (IQR 8.7 - 20.8). Thirteen patients (45%) were previously treated surgically while 9 patients (31%) had previous radiation therapy. All patients underwent surgery: en bloc resection was passible in 4 patients (14 %), seventeen patients (59%) were treated with gross total resection while 8 patients (27%) underwent subtotal resection. Tumor volume was associated with a significantly higher risk of intraoperative complications (p < 0.01). Nineteen patients (65%) received adjuvant high-energy particle therapy. The median follow-up was 26 months (IQR 11 - 44). Twelve patients (41%) had local recurrence of disease. Patients treated with adjuvant high-energy particle therapy had a significant higher local control than patients who received photons or no adjuvant treatment (p = 0.01). Recurrence was the only factor significantly associated with worse DSS (p = 0.03 – OR 1.7), being the survival of the group of patients with recurrent disease 58.3% while the survival of the group of patients with no recurrent disease was 100%. Post-operative high-energy particle therapy improved local control in patients with cervical chordoma after surgical resection. Increased tumor volume was associated with increased risk of intraoperative complications. Recurrence of the disease was the only factor significantly associated with disease mortality

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence. Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated. The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells. Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection

In the last years, 3d printing has progressively grown and it has reached a solid role in clinical practice. The main applications brought by 3d printing in orthopedic surgery are: preoperative planning, custom-made surgical guides, custom-made im- plants, surgical simulation, and bioprinting. The replica of the patient's anatomy, starting from the elaboration of medical volumetric images (CT, MRI, etc.), allows a progressive extremization of treatment personalization that could be tailored for every single patient. In complex cases, the generation of a 3d model of the patient's anatomy allows the surgeons to better understand the case — they can almost “touch the anatomy” —, to perform a more ac- curate preoperative planning and, in some cases, to perform device positioning before going to the surgical room (i.e. joint arthroplasty). 3d printing is also commonly used to produce surgical cutting guides, these guides are positioned intraoperatively on given landmarks to guide the surgeon to perform a specific surgical act (bone osteotomy, bone resection, implant position, etc.). In total knee arthroplasty, custom-made cutting guides have been developed to help the surgeon align the femoral and tibial components to the pre-arthritic condition with- out the use of the intramedullary femoral guide. 3d printed custom-made implants represent an emerging alternative to biological reconstructions especially after oncologic resection surgery or in case of complex arthroplasty revision surgery. Custom-made implants are designed to re- place the original shape and size of the patient's bone and they allow an extreme personalization of the treatment for every single patient. Patient-specific surgical simulation is a new frontier that promises great benefits for surgical training. a solid 3d model of the patient's anatomy can faithfully reproduce the surgical complexity of the patient and it allows to generate surgical simulators with increasing difficulty to adapt the difficulties of the course with the level of the trainees performing structured training paths: from the “simple” case to the “complex” case

Primary bone tumors are rare, complex and highly heterogeneous. Its diagnostic and treatment are a challenge for the multidisciplinary team. Developments on tumor biomarkers, immunohistochemistry, histology, molecular, bioinformatics, and genetics are fundamental for an early diagnosis and identification of prognostic factors. The personalized medicine allows an effective patient tailored treatment. The bone biopsy is essential for diagnosis. Treatment may include systemic therapy and local therapy. Frequently, a limb salvage surgery includes wide resection and reconstruction with endoprosthesis, biological or composites. The risk for local recurrence and distant metastases depends on the primary tumor and treatment response. Cancer patients are living longer and bone metastases are increasing. Bone is the third most frequently location for distant lesions. Bone metastases are associated to pain, pathological fractures, functional impairment, and neurological deficits. It impacts survival and patient quality of life. The treatment of metastatic disease is a challenge due to its complexity and heterogeneity, vascularization, reduced size and limited access. It requires a multidisciplinary treatment and depending on different factors it is palliative or curative-like treatment. For multiple bone metastases it is important to relief pain and increases function in order to provide the best quality of life and expect to prolong survival. Advances in nanotechnology, bioinformatics, and genomics, will increase biomarkers for early detection, prognosis, and targeted treatment effectiveness. We are taking the leap forward in precision medicine and personalized care

Extensive bone defects, caused by severe trauma or resection of large bone tumors, are difficult to treat. Regenerative medicine, including stem cell transplantation, may provide a novel solution for these intractable problems and improve the quality of life in affected patients. Adipose-derived stromal/stem cells (ASCs) have been extensively studied as cell sources for regenerative medicine due to their excellent proliferative capacity and the ability to obtain a large number of cells with minimal donor morbidity. However, the osteogenic potential of ASCs is lower than that of bone marrow-derived stromal/stem cells. To address this disadvantage, our group has employed various methods to enhance osteogenic differentiation of ASCs, including factors such as bone morphogenetic protein or Vitamin D, coculture with bone marrow stem cells, VEGF transfection, and gene transfer of Runx-2 and osterix. Recently, we mined a marker that can predict the osteogenic potential of ASC clones and also investigated the usefulness of the molecule as the enhancer of osteogenic differentiation of ASCs as well as its mechanism of action. Through RNA-seq gene analysis, we discovered that GSTT1 was the most distinguished gene marker between highly osteogenic and poorly osteogenic ASC clones. Knockdown of GSTT1 in high osteogenic ASCs by siGSTT1 treatment reduced mineralized matrix formation while GSTT1 overexpression by GSTT1 transfection or GSTT1 recombinant protein treatment enhanced osteogenic differentiation of low osteogenic ASCs. Metabolomic analysis confirmed significant changes of metabolites related to bone differentiation in ASCs transfected with GSTT1. A high total antioxidant capacity, low levels of cellular reactive oxygen species and increased GSH/GSSG ratios were also detected in GSTT1- transfected ASCs. GSTT1 can be a useful marker to screen the highly osteogenic ASC clones and also a therapeutic factor to enhance the osteogenic differentiation of poorly osteogenic ASC clones

Bone defects and fractures, caused by injury, trauma or tumour resection require hospital treatment and temporary loss of mobility, representing an important burden for societies and health systems worldwide. Autografts are the gold standard for promoting new bone formation, but these may provide insufficient material and lead to donor site morbidity and pain. We previously showed that Fibrinogen (Fg) scaffolds promote bone regeneration in vivo (1), and that modifying them with 10mM of Magnesium (Mg) ions modulates macrophage response in vitro and in vivo (2). Also, we showed that Extracellular Vesicles (EV) secreted by Dendritic Cells (DC) recruit Mesenchymal Stem/Stromal Cells (MSC)(3). Herein, we aim to functionalize FgMg scaffolds with DC-EV, to promote recruitment and osteogenic differentiation of MSC. Scaffolds were produced by freeze-drying (2). Ethical permission was sought for all studies. Primary human peripheral blood monocyte-derived DC were cultured, their secreted EV were isolated by differential (ultra)-centrifugation and characterised by transmission electron microscopy and nanoparticle tracking analysis (3). Bone marrow MSC were used to determine the impact of EV-functionalized scaffolds through migration assays and their osteogenic differentiation was assessed by Alizarin Red staining. Fg and FgMg scaffolds functionalized with EV were characterized. Fg and FgMg scaffolds functionalized with DC-secreted EV were more efficient at recruiting MSC than scaffolds alone. MSC cultured on FgMg scaffolds showed significantly increased calcium deposits, in comparison with those cultured on Fg scaffolds. Fg scaffold modification by Mg promotes MSC osteogenic differentiation, while their functionalization with DC-secreted EV acts to promote MSC recruitment. This renders the FgMg-EV functionalized scaffolds an attractive material to promote new bone formation. Acknowledgments: Work funded by Orthoregeneration Network (ON Pilot Grant Spine 2021, EVS4Fusion). MCT supported by ERASMUS+ program

Introduction and Objective. Curative resection of proximal humerus tumours is now possible in this era of limb salvage with endoprosthetic replacement considered as the preferred reconstructive option. However, it has also been linked with mechanical and non-mechanical failures such as stem fracture and aseptic loosening. One of the challenges is to ensure that implants will endure the mechanical strain under physiological loading conditions, especially crucial in long surviving patients. The objective is to investigate the effect of varying prosthesis length on the bone and implant stresses in a reconstructed humerus-prosthesis assembly after tumour resection using finite element (FE) modelling. Methods. Computed tomography (CT) scans of 10 humeri were processed in Mimics 17 to create three-dimensional (3D) cortical and cancellous solid bone models. Endoprostheses of different lengths manufactured by Stryker were modelled using Solidworks 2020. The FE models were divided into four groups namely group A consisting of the intact humerus and groups B, C and D composed of humerus-prosthesis assemblies with a body length of 40, 100 and 120 mm respectively and were meshed using linear 4-noded tetrahedral elements in 3matic 13. The models were then imported into Abaqus CAE 6.14. Isotropic linear elastic behaviour with an elastic modulus of 13400, 2000 and 208 000 MPa were assigned to the cortical bone, cancellous bone and prosthesis respectively and a Poisson's ratio of 0.3 was assumed for each material. To represent the lifting of heavy objects and twisting motion, a tensile load of 200 N for axial loading and a 5 Nm torsional load for torsional loading was applied separately to the elbow joint surface with the glenohumeral joint fixed and with all contact interfaces defined as fully bonded. A comparative analysis against literature was performed to validate the intact model. Statistical analysis of the peak von Mises stress values collected from predicted stress contour plots was performed using a one-way repeated measure of analysis of variance (with a Bonferroni post hoc test) using SPSS Statistics 26. The average change in stress of the resected models from the intact state were then determined. Results. The validation of the intact humerus displayed a good agreement with literature values. The peak bone stress occurred distally above the coronoid and olecranon fossa closer to the load application region in the intact and resected bone models with a significant amount of loading borne by the cortical bone, while the peak implant stress occurred at the bone-prosthesis contact interface under both loading conditions. Based on the results obtained, a statistically significant difference (p =.013) in implant stress was only seen to occur between groups B and C under tension. Results illustrate initiation of stress shielding with the bone bearing lesser stress with increasing resection length which may eventually lead to implant failure by causing bone resorption according to Wolff's law. The peak implant stress under torsion was 3–5 times the stress under tension. The best biomechanical behaviour was exhibited in Group D, having the least average change in stress from the intact model, 5% and 3.8% under tension and torsion respectively. It can be deduced that the shorter the prosthesis length, the more pronounced the effect on cortical bone remodelling. With the maximum bone and implant stresses obtained being less than their yield strength, it can be concluded that the bone-implant construct is safe from failure. Conclusions. The developed FE models verified the influence of varying the prosthesis length on the bone and implant stresses and predicted signs of stress shielding in longer endoprostheses. By allowing for 2 cm shortening in the upper extremity and post-surgical scarring, it is beneficial to err towards a shorter endoprosthesis

Critical-sized bone defects can result from trauma, inflammation, and tumor resection. Such bone defects, often have irregular shapes, resulting in the need for new technologies to produce suitable implants. Bioprinting is an additive manufacturing method to create complex and individualised bone constructs, which can already include vital cells. In this study, we established an extrusion-based printing technology to produce osteoinductive scaffolds based on polycaprolactone (PCL) combined with calcium phosphate, which is known to induce osteogenic differentiation of stem cells. The model was created in python based on the signed distance functions. The shape of the 3D model is a ring with a diameter of 20 mm and a height of 10 mm with a spongiosa-like structure. The interconnected irregular pores have a diameter of 2 mm +/− 0.2 mm standard deviation. Extrusion-based printing was performed using the BIO X6. To produce the bioink, PCL (80 kDa) was combined with calcium phosphate nanopowder (> 150 nm particle size) under heating. After printing, 5 × 10. 6. hMSC were seeded on the construct using a rotating incubator. We were able to print a highly accurate ring construct with an interconnected pore structure. The PCL combined with calcium phosphate particles resulted in a precise printed construct, which corresponded to the 3D model. The bioink containing calcium phosphate nanoparticles had a higher printing accuracy compared to PCL alone. We found that hMSC cultured on the construct settled in close proximity to the calcium phosphate particles. The hMSC were vital for 22 days on the construct as demonstrated by life/dead staining. The extrusion printing technology enables to print a mechanically stable construct with a spongiosa-like structure. The porous PCL ring could serve as an outer matrix for implants, providing the construct the stability of natural bone. To extend this technology and to improve the implant properties, a biologised inner structure will be integrated into the scaffold in the future

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

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