Ultrasound supports clinical decision-making in determining the Sanders' skeletal maturity score of the hand.

PURPOSE: The Sanders Scoring System has revolutionized the way we assess the remaining growth potential of the skeleton. However, because it involves radiation exposure, it must be used with caution in children. The purpose of the study was to evaluate whether the Sanders skeletal maturity score (SMS) could be accurately determined using ultrasound (U). METHODS: We took radiographs (R) of the hand and performed U of the thumb and index finger in 115 patients between six and 19 years of age who were undergoing treatment for scoliosis or limb deformities. Paediatric orthopaedic surgeons, a paediatrician, and a paediatric radiologist were evaluated the blinded images. Those classified images are based on the SMS and the Thumb Ossification Composite Index (TOCI). RESULTS: Intrarater reliability was high for SMS and slightly weaker for TOCI, but still significant. Interrater reliability was clear for R and weaker for U in both staging systems. Ultimately, SMS 3 and 7 achieved the highest percentage of concordance (P) of 71.7% and 66.0%, respectively, when U was performed. Combining the clinically relevant groups of SMS 3&4 and SMS 7&8 also significantly increased peak scores (SMS 3 and 4 P = 76.7%; SMS 7 and 8 P = 79.7%). The probabilities of peak scores were significantly weaker when the TOCI score was examined. CONCLUSION: Our study shows that U can be used effectively especially to measure stages 3 and 4 and stages 7 and 8 of SMS. The U method is easy to use and therefore may offer advantages in clinical practice without the need for radiation exposure.

Muscle forces acting on the greater trochanter lead to a dorsal warping of the apophyseal growth plate.

The apophyseal growth plate of the greater trochanter, unlike most other growth plates of the human body, exhibits a curved morphology that results in a divergent pattern resembling an open crocodile mouth on plain antero-posterior radiographs. To quantify the angular alignment of the growth plate and to draw conclusions about the function of the muscles surrounding it, we analyzed 57 MRI images of 51 children and adolescents aged 3-17 years and of six adults aged 18-52 years. We measured the angulation of the plate relative to the horizontal plane (AY angle) and the trajectories of the muscles attaching to the greater trochanter of the proximal femur. From anterior to posterior, the AY angle shows a decrease of 33.44°. In the anterior third, the cartilage is angled at a mean of 51.64°, and in the posterior third, the mean angulation is 18.6°. This indicates that the cartilage in the anterior region of the greater trochanteric apophysis is subject to more vertically oriented force vectors compared to the posterior region, as the growth plates align perpendicular to the force vectors acting on them. Combining the measured muscle trajectories with the physiological cross-sectional areas (PCSA) available from the literature revealed that, in addition to the known internal and external lateral traction ligament systems, a third, dorsally located traction ligament system exists that may be responsible for the dorsal deformation of the AY angle.

Functional adaptation after femoral intertrochanteric valgus osteotomy in Legg-Calvé-Perthes disease.

Legg-Calvé-Perthes disease (LCPD) requires individualized treatment in order to regain a functional hip joint. In severe cases, in which a congruent joint cannot be achieved, other options are necessary in order to improve functionality and prevent early osteoarthritis. Therefore, we analysed the clinical and radiologic outcome of 28 patients after valgus osteotomy of the proximal femur (VOF). We examined the range of hip motion, functionality and health-related quality of life (HRQoL) via modified Harris Hip Score (mHHS) and Kidscreen-10. Radiographic analysis contained quantitative and qualitative measurements of hip morphology. In particular, we correlated the results with the change of the pelvic-femoral angle (PFA). PFA was defined as the angle between the anatomical diaphyseal line of the femur and a vertical line through the pelvis. The mean follow-up was 5.5 years. Patients showed high mHHS and good HRQoL postoperatively. An increase in ROM with an improvement of 30.5° abduction and 10.3° internal rotation was evident. PFA correlated with adduction contracture and improved significantly after surgery. In consideration of careful patient selection, VOF showed a positive effect on ROM, pain, HRQoL, radiographic congruence and outcome. We identified the age at surgery and an increasing adduction contracture-objectified by a decreased PFA-as a prognostic factor.

Femur reconstruction in 3D ultrasound for orthopedic surgery planning.

PURPOSE: Derotation varisation osteotomy of the proximal femur in pediatric patients usually relies on 2-dimensional X-ray imaging, as CT and MRI still are disadvantageous when applied in small children either due to a high radiation exposure or the need of anesthesia. This work presents a radiation-free non-invasive tool to 3D-reconstruct the femur surface and measure relevant angles for orthopedic diagnosis and surgery planning from 3D ultrasound scans instead. METHODS: Multiple tracked ultrasound recordings are segmented, registered and reconstructed to a 3D femur model allowing for manual measurements of caput-collum-diaphyseal (CCD) and femoral anteversion (FA) angles. Novel contributions include the design of a dedicated phantom model to mimic the application ex vivo, an iterative registration scheme to overcome movements of a relative tracker only attached to the skin, and a technique to obtain the angle measurements. RESULTS: We obtained sub-millimetric surface reconstruction accuracy from 3D ultrasound on a custom 3D-printed phantom model. On a pre-clinical pediatric patient cohort, angular measurement errors were [Formula: see text] and eventually [Formula: see text] for CCD and FA angles, respectively, both within the clinically acceptable range. To obtain these results, multiple refinements of the acquisition protocol were necessary, ultimately reaching success rates of up to 67% for achieving sufficient surface coverage and femur reconstructions that allow for geometric measurements. CONCLUSION: Given sufficient surface coverage of the femur, clinically acceptable characterization of femoral anatomy is feasible from non-invasive 3D ultrasound. The acquisition protocol requires leg repositioning, which can be overcome using the presented algorithm. In the future, improvements of the image processing pipeline and more extensive surface reconstruction error assessments could enable more personalized orthopedic surgery planning using cutting templates.

NGS-Panel Diagnosis Developed for the Differential Diagnosis of Idiopathic Toe Walking and Its Application for the Investigation of Possible Genetic Causes for the Gait Anomaly.

Idiopathic toe walking (ITW) describes a condition affecting approximately 4.5% of children. Toe walking is an accompanying symptom for many hereditary disorders. This retrospective study uses next-generation sequencing-panel-diagnosis to investigate the feasibility of genetic testing to research the possible genetic causes of ITW and for differential diagnosis. Data were taken from our inhouse database, the minimum age for participants was 3 years. Underlying neurological or orthopaedic conditions were tested for and ruled out prior to diagnosing ITW. Patients, who experienced complications before, during or immediately after birth, children with autism, and patients toe walking less than 50% of the time were excluded. Eighty-nine patients were included in the study, in which 66 (74.2%) patients were boys and 23 (25.8%) girls. Mean age at testing was 7.7 years (range: 3-17 years). Fifteen of the 89 patients included in the study (16.9%) had a genetic variant identified as likely pathogenic or pathogenic by the genetics laboratory. Additionally, we found 129 variants of uncertain significance. About 65.2% of patients showed a pes cavus foot deformity, 27% of patients reportedly had at least one relative who also displayed the gait anomaly, and 37.1% had problems with their speech development. Despite the limitations of the sample size and the scope of our genetic testing targets, our results indicate that research into the genetic causes of ITW could better our understanding of the causes of ITW in otherwise healthy children, to help develop novel methods to detect serious conditions early. ITW could be an early onset symptom for further hereditary conditions.

Intrainstitutional Changes of the Treatment of Supracondylar Humerus Fracture in Children over a Period of 9 Years.

To assess changes in treatment modalities for supracondylar humerus fractures (SCHFs) at a large pediatric university hospital, we analyzed patient data from 2014 to 2022. A total of 233 SCHFs treated surgically at our hospital were included. To evaluate postoperative outcome and quality of life, DASH and EuroQol-5D-Y questionnaires were sent to patients. In addition to a significant fluctuation in fracture severity, we found an increase in training interventions (more surgeries were performed by trainees) and a significant decrease in surgery times after 2016. From 2020, there was a significant shift in the type of surgical method away from closed reduction with elastic stable intramedullary nailing (ESIN) and towards closed reduction and crossed K-wire osteosynthesis (CRK). Surgeries performed in the morning and evening hours increased, while those performed in the afternoon and after midnight decreased. After a mean follow-up of 4 years, there was no difference in elbow function between ESIN and open reduction and K-wires (ORK). Treatment with ESIN was equivalent to ORK in terms of function, at least in the medium-term follow-up. In summary, the combination of shifting treatment from SCHF to daytime hours, increasing trainee participation and using cross K-wire fixation instead of ESIN had no negative impact on surgery times. In our setting, these measures have reduced resource utilization and increased efficiency without compromising patient care.

Minced Cartilage Is a One-Step Cartilage Repair Procedure for Small Defects in the Knee-A Systematic-Review and Meta-Analysis.

Purpose: Approximately 60% of patients undergoing arthroscopy of the knee present with chondral defects. If left untreated, osteochondral lesions can trigger an early onset of osteoarthritis. Many cartilage repair techniques are mainly differentiated in techniques aiming for bone marrow stimulation, or cell-based methods. Cartilage repair can also be categorized in one- and two-stage procedures. Some two-stage procedures come with a high cost for scaffolds, extensive cell-processing, strict regulatory requirements, and limited logistical availability. Minced cartilage, however, is a one-stage procedure delivering promising results in short term follow-up, as noted in recent investigations. However, there is no available literature summarizing or synthesizing clinical data. The purpose of this study was to analyze and synthesize data from the latest literature in a meta-analysis of outcomes after the minced cartilage procedure and to compare its effectiveness to standard repair techniques. Methods: We conducted a systematic review searching the Cochrane, PubMed, and Ovid databases. Inclusion criteria were the modified Coleman methodology Score (mCMS) >60, cartilaginous knee-joint defects, and adult patients. Patient age < 18 years, biomechanical and animal studies were excluded. Relevant articles were reviewed independently by referring to title and abstract. In a systematic review, we compared three studies and 52 patients with a total of 63 lesions. Results: Analysis of Knee Injury and Osteoarthritis Outcome Score (KOOS) sub scores at 12 and 24 months showed a significant score increase in every sub score. Highest mean difference was seen in KOOS sport, lowest in KOOS symptoms (12 month: KOOS sport (Mean difference: 35.35 [28.16, 42.53]; p < 0.0001), lowest in KOOS symptoms (Mean difference: 20.12 [15.43, 24.80]; p < 0.0001)). A comparison of International Knee Documentation Committee (IKDC ) scores visualized a significant score increase for both time points too ((12 month: pooled total mean: 73.00 ± 14.65; Mean difference: 34.33 [26.84, 41.82]; p < 0.00001) (24 month: pooled total mean: 77.64 ± 14.46; mean difference: 35.20 [39.49, 40.92]; p < 0.00001)). Conclusion: Due to no need for separate cell-processing, and thanks to being a one-step procedure, minced cartilage is a promising method for cartilage repair in small defect sizes (mean 2.77 cm2, range 1.3−4.7 cm2). However, the most recent evidence is scarce, and takes only results two years post-surgery into account. Summarized, minced cartilage presents nearly equal short-term improvement of clinical scores (IKDC, KOOS) compared to standard cartilage repair techniques.

Clinical examination and patients' history are not suitable for neonatal hip screening.

Purpose: To assess the percentage of missed developmental dysplasia of the hip, which escape the German criteria for newborn hip high-risk screening, we analyzed our data gained from the general neonatal sonographic hip screening performed at our department. The aim of the study was to determine the number of potentially belatedly treated developmental dysplasia of the hip. Methods: The data from 1145 standardized newborn hip ultrasound examinations according to the Graf technique were analyzed retrospectively comparing findings for general neonatal sonographic hip screening and high-risk screening subgroups. Results: We diagnosed developmental dysplasia of the hip in 18 of the 1145 newborns via ultrasound. A total of 10 out of 18 developmental dysplasia of the hip would have been missed by high-risk screening, which corresponds to a proportion of 55.6% false-negative results. The sensitivity of high-risk screening was only 44.4% and specificity, 78.3%. The positive predictive value was 3.2%. Family history as a screening criterion yielded false-negative results in 77.8% and false-positive results in 16.8%. In all, 83.3% of the children who were born with developmental dysplasia of the hip but not from breech position as a risk factor were false negative. The clinical examination was false negative in 88.9% and false positive in 0.6%. Conclusion: High-risk screening detected less than every second developmental dysplasia of the hip, rendering the first month as the most effective treatment window unavailable for inapparent dysplastic hips, potentially resulting in the need for more invasive treatment. Due to the high sensitivity of ultrasound in the detection of developmental dysplasia of the hip, we recommend to replace the current German high-risk screening guidelines with a general newborn screening for all neonates using Graf ultrasound in the first week of life. Level of evidence: Level II.

Lag screw osteosynthesis of simple olecranon fractures: A biomechanical comparative study.

Olecranon fractures are most frequently stabilized by tension band wiring (TBW), which unfortunately leads to relevant implant removal rates due to K-wire migration and soft tissue irritation. As lag screw osteosynthesis (LSO) might be a gentle and effective alternative in simple fracture patterns, the goal of the present study was to biomechanically compare LSO with TBW in simple olecranon fractures at a cadaver model. A simple olecranon fracture (Mayo type IIA) was created in eight pairs of human cadaver elbows, which were pairwise fixed by either TBW or two transcortical 4.0 mm lag screws. Biomechanical testing was conducted as a pulling force, applied to the triceps tendon in a 90° position. First, cyclic loading between 10 and 300 N was performed for 50,000 cycles. Afterward, maximum load was raised by 0.02 N/cycle until construct failure, what was defined as displacement >2 mm. Besides fracture displacement, failure cycle and failure load, the modes of failure were analyzed. Within the first five cycles, there was no significant difference in displacement (median TBW: 0.2 mm; LSO: 0.5 mm; p = 0.091). Both after 2000 (median TBW: 0.2 mm; LSO: 0.6 mm; p = 0.042) and after 20,000 cycles (median TBW: 0.4 mm; LSO: 0.9 mm; p = 0.027), the difference was significant. Failure cycle (median TBW: 72,639 cycles; LSO: 43,429 cycles; p = 0.017) and failure load (median TBW: 702 N; LSO: 303 N; p = 0.025) differed significantly as well. TBW mostly (6/8) failed at the lock of the cerclage wire, whereas most LSO constructs (5/8) failed as a pullout of the proximal fragment. In conclusion, to our biomechanical findings at human cadaver specimens, simple olecranon fractures treated by LSO show higher dislocation rates and lower failure loads compared to conventional TBW and mostly fail by pullout of the proximal fragment.

Autologous Minced Cartilage Implantation for Arthroscopic One-Stage Treatment of Osteochondritis Dissecans of the Elbow.

This Technical Note describes the full arthroscopic one-stage treatment of high-grade osteochondritis dissecans of the humeral capitellum of the elbow joint by means of minced cartilage implantation.

Hydrogel-based autologous chondrocyte implantation leads to subjective improvement levels comparable to scaffold based autologous chondrocyte implantation.

PURPOSE: Scaffold-based autologous chondrocyte implantation is a well-established treatment for cartilage defects in the knee joint. Hydrogel-based autologous chondrocyte implantation using an in situ polymerizable biomaterial is a relatively new treatment option for arthroscopic cartilage defects. It is therefore important to determine if there are significant differences in the outcomes. The aim of this study is to compare the outcomes (using subjective parameters) of hydrogel-based autologous chondrocyte implantation (NOVOCART® Inject) with the outcomes of scaffold based autologous chondrocyte Implantation (NOVOCART® 3D) using biphasic collagen scaffold. METHODS: The data of 50 patients, which were paired with 25 patients in each treatment group, was analyzed. The main parameters used for matching were gender, number of defects and localization. Both groups were compared based on Visual Analogue Scale (VAS) and subjective IKDC scores, both of which were examined pre-operatively and after 6, 12 and 24 months. RESULTS: Significant benefits in both VAS and IKDC scores after 2 years of follow-up in both groups were found. Comparing the groups, the results showed that in the hydrogel-based autologous chondrocyte implantation group, significant changes in IKDC scores are measurable after 6 months, while it takes 12 months until they are seen in the scaffold based autologous chondrocyte group. CONCLUSION: Hydrogel-based autologous chondrocyte and scaffold based autologous chondrocyte show comparable improvements and significant benefits to the patients' subjective well-being after a 2-year-follow-up. LEVEL OF EVIDENCE: III.

A humanised rat model of osteosarcoma reveals ultrastructural differences between bone and mineralised tumour tissue.

Current xenograft animal models fail to accurately replicate the complexity of human bone disease. To gain translatable and clinically valuable data from animal models, new in vivo models need to be developed that mimic pivotal aspects of human bone physiology as well as its diseased state. Above all, an advanced bone disease model should promote the development of new treatment strategies and facilitate the conduction of common clinical interventional procedures. Here we describe the development and characterisation of an orthotopic humanised tissue-engineered osteosarcoma (OS) model in a recently genetically engineered x-linked severe combined immunodeficient (X-SCID) rat. For the first time in a genetically modified rat, our results show the successful implementation of an orthotopic humanised tissue-engineered bone niche supporting the growth of a human OS cell line including its metastatic spread to the lung. Moreover, we studied the inter- and intraspecies differences in ultrastructural composition of bone and calcified tissue produced by the tumour, pointing to the crucial role of humanised animal models.

A humanized orthotopic tumor microenvironment alters the bone metastatic tropism of prostate cancer cells.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, and bone is the most frequent site of metastasis. The tumor microenvironment (TME) impacts tumor growth and metastasis, yet the role of the TME in PCa metastasis to bone is not fully understood. We used a tissue-engineered xenograft approach in NOD-scid IL2Rγnull (NSG) mice to incorporate two levels of humanization; the primary tumor and TME, and the secondary metastatic bone organ. Bioluminescent imaging, histology, and immunohistochemistry were used to study metastasis of human PC-3 and LNCaP PCa cells from the prostate to tissue-engineered bone. Here we show pre-seeding scaffolds with human osteoblasts increases the human cellular and extracellular matrix content of bone constructs, compared to unseeded scaffolds. The humanized prostate TME showed a trend to decrease metastasis of PC-3 PCa cells to the tissue-engineered bone, but did not affect the metastatic potential of PCa cells to the endogenous murine bones or organs. On the other hand, the humanized TME enhanced LNCaP tumor growth and metastasis to humanized and murine bone. Together this demonstrates the importance of the TME in PCa bone tropism, although further investigations are needed to delineate specific roles of the TME components in this context.

Establishment of a Pediatric Surgical Unit at a University Hospital in Eastern Africa.

INTRODUCTION: Ethiopia is a rapidly developing country in Eastern Africa. In total, 43.2% of the population are younger than 15. In contrast, until a few years ago, pediatric surgery was only available in Addis Ababa. Now, Ethiopia is making great efforts to improve the care of children who require surgery. JimmaChild was established to set up a pediatric surgery in Jimma. MATERIAL AND METHODS: JimmaChild developed from a scientific collaboration between Jimma University (JU) and Ludwig-Maximilians-University. The project was developed and realized by Ethiopian and German colleagues. A curriculum was written for this purpose. The pediatric surgical training of the fellows was carried out on-site by German pediatric surgeons. RESULTS: A new pediatric surgery was established at JU with its own operating room, ward, and staff. After two and a half years, two fellows completed their final examinations as pediatric surgeons. Among others, 850 elective surgeries were performed, 82% assisted by the German colleagues. The German colleagues rated the preparation for the trip, the on-site support, and the professional progress of the fellows mostly as good to very good. Reported problems in the program flow were also recognized and solved in part. CONCLUSIONS: The best possible integration of the project into existing structures was achieved by close cooperation of Ethiopian and German colleagues during the project development. Problems were identified and addressed early on by external monitoring. As the project responsibility was mainly with the Ethiopian colleagues, a department was created that now exists independently of external funding and trains its own fellows.

Low-profile double plating of unstable osteoporotic olecranon fractures: a biomechanical comparative study.

BACKGROUND: In the treatment of unstable olecranon fractures, anatomically preshaped locking plates exhibit superior biomechanical results compared with tension band wiring. However, posterior plating (PP) still is accompanied by high rates of plate removal because of soft-tissue irritation and discomfort. Meanwhile, low-profile plates precontoured for collateral double plating (DP) are available and enable muscular soft-tissue coverage combined with angular-stable fixation. The goal of this study was to biomechanically compare PP with collateral DP for osteosynthesis of unstable osteoporotic fractures. METHODS: A comminuted displaced Mayo type IIB fracture was created in 8 osteoporotic pairs of fresh-frozen human cadaveric elbows. Pair-wise angular stable fixation was performed by either collateral DP or PP. Biomechanical testing was conducted as a pulling force to the triceps tendon in 90° of elbow flexion. Cyclical load changes between 10 and 300 N were applied at 4 Hz for 50,000 cycles. Afterward, the maximum load was raised by 0.02 N/cycle until construct failure, which was defined as displacement > 2 mm. Besides failure cycles and failure loads, modes of failure were analyzed. RESULTS: Following DP, a median endurance of 65,370 cycles (range, 2-83,121 cycles) was recorded, which showed no significant difference compared with PP, with 69,311 cycles (range, 150-81,938 cycles) (P = .263). Failure load showed comparable results as well, with 601 N (range, 300-949 N) after DP and 663 N (range, 300-933 N) after PP (P = .237). All PP constructs and 3 of 8 DP constructs failed by proximal fragment cutout, whereas 5 of 8 DP constructs failed by bony triceps avulsion. CONCLUSION: Angular-stable DP showed comparable biomechanical stability to PP in unstable osteoporotic olecranon fractures under high-cycle loading conditions. Failure due to bony triceps avulsion following DP requires further clinical and biomechanical investigation, for example, on suture augmentation or different screw configurations.

Injury patterns following simple elbow dislocation: radiological analysis implies existence of a pure valgus dislocation mechanism.

INTRODUCTION: The aim of the present study was to analyze the injury pattern and thus the dislocation mechanism after simple elbow dislocation using radiographs and magnetic resonance imaging (MRI) data sets. MATERIALS AND METHODS: The MRI data sets of 64 patients with a mean age of 44 years (18-77 years) were analyzed retrospectively. The inclusion criteria for the study were (1) radiograph with confirmed simple elbow dislocation, (2) low-energy trauma, (3) MRI of the affected elbow ≤ 3 weeks after trauma. The dislocation direction was determined using radiographs. The integrity of the lateral collateral ligament complex (LCLC), common extensor origin (CEO), anterior capsule (AC), medial collateral ligament (MCL), and common flexor origin (CFO) as well as the joint congruity were assessed based on MRI. RESULTS: 34 patients (53%) had a posterolateral, 26 patients (41%) a posterior, and 4 patients (6%) a posteromedial dislocation. LCLC and AC were affected in 64 out of 64 patients (100%). MCL was affected in 58 patients (91%). CEO were affected in 25 patients (39%) and the CFO in 20 patients (31%). In 11 patients (17%) the injury pattern was more pronounced medially than laterally (MCL, CFO, LCLC), with 2 of these patients exhibiting only a partial LCLC tear. All cases with joint incongruency (n = 12, 19%) showed CEO and/or CFO involvement. CONCLUSIONS: Simple elbow dislocation leads to a very heterogeneous spectrum of soft tissue injury pattern. A small proportion of patients showed medially pronounced injury patterns. These findings strongly indicate existence of a "reversed Horii circle" with an underlying valgus mechanism (medial force induction) originating and continuing from medial to anterior.

Biodegradable magnesium vs. polylactide pins for radial head fracture stabilization: a biomechanical study.

BACKGROUND: Biodegradable implants have gained increasing importance for the fixation of simple displaced radial head fractures to supersede implant removal and to minimize cartilage destruction. Commonly used polylactide pins still lead to higher rates of secondary loss of reduction compared with metal implants. Alternatively, implants made from a magnesium alloy meanwhile are available in a pin design that hypothetically could perform better than polylactide pins. Because biomechanical data of clinical applications are lacking, the goal of the present study was to biomechanically compare magnesium pins to polylactide pins using a Mason type II radial head fracture model. METHODS: Fourteen pairs of fresh-frozen human cadaver radii with a standardized Mason type II radial head fracture were stabilized either by two 2.0-mm polylactide pins (PPs) or two 2.0-mm magnesium pins (MPs). Biomechanical in vitro testing was conducted as 10 cycles of static loading at 0.1 Hz axially and transversally between 10 and 50 N. Afterward, loosening was tested by dynamic load changes at 4 Hz up to 100,000 cycles. Early fracture displacement was measured after 10,000 cycles. Afterward, maximum loads were raised every 10,000 cycles by 15 N until construct failure, which was defined as fracture displacement ≥2 mm. RESULTS: MP osteosynthesis showed a tendency toward higher primary stability on both axial (MP: 0.19 kN/mm, PP: 0.11 kN/mm; P = .068) and transversal loading (MP: 0.11 kN/mm, PP: 0.10 kN/mm; P = .068). Early fracture displacement was significantly higher following PP osteosynthesis (MP: 0.3 mm, PP: 0.7 mm; P = .030). The superiority of MP was also significant during cyclic loading, represented in a higher failure cycle (MP: 30,684, PP: 5113; P = .009) and in higher failure loads (MP: 95 N, PP: 50 N; P = .024). CONCLUSION: According to our findings, in simple radial head fractures, osteosynthesis with magnesium pins show superior biomechanical properties compared with fractures treated by polylactide pins. Prospective investigations should follow to evaluate clinical outcomes and resorption behavior.

SOX9 Knockout Induces Polyploidy and Changes Sensitivity to Tumor Treatment Strategies in a Chondrosarcoma Cell Line.

As most chemotherapeutic drugs are ineffective in the treatment of chondrosarcoma, we studied the expression pattern and function of SOX9, the master transcription factor for chondrogenesis, in chondrosarcoma, to understand the basic molecular principles needed for engineering new targeted therapies. Our study shows an increase in SOX9 expression in chondrosarcoma compared to normal cartilage, but a decrease when the tumors are finally defined as dedifferentiated chondrosarcoma (DDCS). In DDCS, SOX9 is almost completely absent in the non-chondroid, dedifferentiated compartments. CRISPR/Cas9-mediated knockout of SOX9 in a human chondrosarcoma cell line (HTB94) results in reduced proliferation, clonogenicity and migration, accompanied by an inability to activate MMP13. In contrast, adhesion, apoptosis and polyploidy formation are favored after SOX9 deletion, probably involving BCL2 and survivin. The siRNA-mediated SOX9 knockdown partially confirmed these results, suggesting the need for a certain SOX9 threshold for particular cancer-related events. To increase the efficacy of chondrosarcoma therapies, potential therapeutic approaches were analyzed in SOX9 knockout cells. Here, we found an increased impact of doxorubicin, but a reduced sensitivity for oncolytic virus treatment. Our observations present novel insight into the role of SOX9 in chondrosarcoma biology and could thereby help to overcome the obstacle of drug resistance and limited therapy options.

A 3D-printed biomaterials-based platform to advance established therapy avenues against primary bone cancers.

In this study we developed and validated a 3D-printed drug delivery system (3DPDDS) to 1) improve local treatment efficacy of commonly applied chemotherapeutic agents in bone cancers to ultimately decrease their systemic side effects and 2) explore its concomitant diagnostic potential. Thus, we locally applied 3D-printed medical-grade polycaprolactone (mPCL) scaffolds loaded with Doxorubicin (DOX) and measured its effect in a humanized primary bone cancer model. A bioengineered species-sensitive orthotopic humanized bone niche was established at the femur of NOD-SCID IL2Rγnull (NSG) mice. After 6 weeks of in vivo maturation into a humanized ossicle, Luc-SAOS-2 cells were injected orthotopically to induce local growth of osteosarcoma (OS). After 16 weeks of OS development, a biopsy-like defect was created within the tumor tissue to locally implant the 3DPDDS with 3 different DOX loading doses into the defect zone. Histo- and morphological analysis demonstrated a typical invasive OS growth pattern inside a functionally intact humanized ossicle as well as metastatic spread to the murine lung parenchyma. Analysis of the 3DPDDS revealed the implants' ability to inhibit tumor infiltration and showed local tumor cell death adjacent to the scaffolds without any systemic side effects. Together these results indicate a therapeutic and diagnostic capacity of 3DPDDS in an orthotopic humanized OS tumor model.