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.

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.

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.

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.

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.

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.

The acromioclavicular ligament shows an early and dynamic healing response following acute traumatic rupture.

PURPOSE: Symptomatic horizontal instability is clinically relevant following acute acromioclavicular joint dislocations. However, the intrinsic healing response is poorly understood. The present study sought to investigate time-dependent healing responses of the human acromioclavicular ligament following acute traumatic rupture. METHODS: Biopsies of the acromioclavicular ligament were obtained from patients undergoing surgical treatment for acute acromioclavicular joint dislocations. Specimens were stratified by time between trauma and surgery: group 1, 0-7 days (n = 5); group 2, 8-14 days (n = 6); and group 3, 15-21 days (n = 4). Time-dependent changes in cellularity, collagen (type 1 and 3) concentration, and histomorphological appearance were evaluated for the rupture and intact zone of the acromioclavicular ligament. RESULTS: Group 1 was characterized by cellular activation and early inflammatory response. The rupture zone exhibited a significantly higher count of CD68-positive cells than the intact zone (15.2 vs 7.4; P ≤ 0.05). Consistently, synovialization of the rupture end was observed. Within the second week, the rupture zone was subject to proliferation showing more fibroblast-like cells than the intact zone (66.8 vs 43.8; P ≤ 0.05) and a peak of collagen type 3 expression (group 1: 2.2 ± 0.38, group 2: 3.2 ± 0.18, group 3: 2.8 ± 0.57; P ≤ 0.05). Signs of consolidation and early remodeling were seen in the third week. CONCLUSIONS: The acromioclavicular ligament exhibits early and dynamic healing responses following acute traumatic rupture. Our histological findings suggest that surgical treatment of acute ACJ dislocations should be performed as early as possible within a timeframe of 1 week after trauma to exploit the utmost biological healing potential. Prospective clinical studies are warranted to investigate whether early surgical treatment of ACJ dislocations translates into clinical benefits.

Biomechanical comparison of biodegradable magnesium screws and titanium screws for operative stabilization of displaced capitellar fractures.

BACKGROUND: Displaced fractures of the humeral capitellum are commonly treated operatively and fixed by titanium screws (TSs) either directly or indirectly. In the case of direct transcartilaginous fixation, biodegradable screws with the ability to be countersunk can be favorable regarding implant impingement and cartilage destruction. Hence, the goal of this study was to biomechanically compare headless compression screws made from titanium with a biodegradable equivalent made from a magnesium alloy. METHODS: This biomechanical in vitro study was conducted on 13 pairs of fresh-frozen human cadaveric humeri, in which a standardized Bryan-Morrey type I fracture was fixed using 2 magnesium screws (MSs) or 2 TSs. First, construct stiffness was measured during 10 cycles of static loading between 10 and 50 N. Second, continuous loading was applied at 4 Hz between 10 and 50 N, increasing the maximum load every 10,000 cycles by 25 N until construct failure occurred. This was defined by fragment displacement >3 mm. RESULTS: Comparison of the 2 screw types showed no differences related to construct stiffness (0.50 ± 0.25 kN/mm in MS group and 0.47 ± 0.13 kN/mm in TS group, P = .701), failure cycle (43,944 ± 21,625 and 41,202 ± 16,457, respectively; P = .701), and load to failure (152 ± 53 N and 150 ± 42 N, respectively; P = .915). CONCLUSION: Biomechanical comparison showed that simple capitellar fractures are equally stabilized by headless compression screws made from titanium or a biodegradable magnesium alloy. Therefore, in view of the advantages of biodegradable implants for transcartilaginous fracture stabilization, their clinical application should be considered and evaluated.

Biomechanical dynamic comparison of biodegradable pins and titanium screws for operative stabilization of displaced radial head fractures.

For radial head osteosynthesis, biodegradable implants are gaining in importance to minimize cartilage destruction and implant impingement and to supersede implant removal. Since loss of reduction and pseudarthrosis remain challenging complications, new implants should at least provide comparable biomechanical properties as commonly used metal implants. The objective of this study was to compare the treatment by polylactide pins to titanium screws and to quantify the produced cartilage defects. Eight pairs of human cadaver radii with a standardized Mason type II fracture were stabilized either by two 2.0-mm polylactide pins or titanium screws. The produced cartilage defects were quantified using an image analyzing software. Quasi-static loading was performed axially and transversally for 10 cycles each between 10 and 50 N. Afterward, implant loosening was tested by axial loading up to 10,000 cycles, followed by load to failure testing. Polylactide pins showed less construct stiffness under axial (p = 0.017) and transversal (p = 0.012) loading, and one polylactide pins construct failed after two cycles of transversal loading. At axial loading, a high correlation between bone mineral density and construct stiffness was observed among polylactide pins (R = 0.667; p = 0.071), which was not seen among titanium screws (R = 0.262; p = 0.531). No difference in implant loosening was recorded after 10,000 cycles (p = 0.237); however, one polylactide pins construct failed after 30 cycles and failure loads were higher for titanium screws (p=0.017). Polylactide pin produced smaller cartilage defects (p=0.012). In conclusion, simple radial head fractures treated by polylactide pins show less biomechanical stability than treated by titanium screws, particularly in osteoporotic bone which might lead to secondary loss of reduction. Due to smaller cartilage defects and equal properties under continuous loading, polylactide pins might represent a gentle alternative in patients with good bone quality making subsequent implant removal redundant.

Recombinant Human Bone Morphogenetic Protein 7 Exerts Osteo-Catabolic Effects on Bone Grafts That Outweigh Its Osteo-Anabolic Capacity.

This study aimed to investigate the effects of recombinant human bone morphogenetic protein (rhBMP-7) on human cancellous bone grafts (BGs) while differentiating between anabolic and catabolic events. Human BGs alone or supplemented with rhBMP-7 were harvested 14 weeks after subcutaneous implantation into NOD/Scid mice, and studied via micro-CT, histomorphometry, immunohistochemistry and flow cytometry. Immunohistochemical staining for human-specific proteins made it possible to differentiate between grafted human bone and newly formed murine bone. Only BGs implanted with rhBMP-7 formed an ossicle containing a functional hematopoietic compartment. The total ossicle volume in the BMP+ group was higher than in the BMP- group (835 mm3 vs. 365 mm3, respectively, p < 0.001). The BMP+ group showed larger BM spaces (0.47 mm vs. 0.28 mm, p = 0.002) and lower bone volume-to-total volume ratio (31% vs. 47%, p = 0.002). Immunohistochemical staining for human-specific proteins confirmed a higher ratio of newly formed bone area (murine) to total area (0.12 vs. 0.001, p < 0.001) in the BMP+ group, while the ratio of grafted bone (human) area to total area was smaller (0.14 vs. 0.34, p = 0.004). The results demonstrate that rhBMP-7 induces BG resorption at a higher rate than new bone formation while creating a haematopoietic niche. Clinicians therefore need to consider the net catabolic effect when rhBMP-7 is used with BGs. Overall, this model indicates its promising application to further decipher BMPs action on BGs and its potential in complex bone tissue regeneration.

A humanized bone microenvironment uncovers HIF2 alpha as a latent marker for osteosarcoma.

The quest for predictive tumor markers for osteosarcoma (OS) has not well progressed over the last two decades due to a lack of preclinical models. The aim of this study was to investigate if microenvironmental modifications in an original humanized in vivo model alter the expression of OS tumor markers. Human bone micro-chips and bone marrow, harvested during hip arthroplasty, were implanted at the flanks of NOD/scid mice. We administered recombinant human bone morphogenetic protein 7 (rhBMP-7) in human bone micro-chips/bone marrow group I in order to modulate bone matrix and bone marrow humanization. Ten weeks post-implantation, human Luc-SAOS-2 OS cells were injected into the humanized tissue-engineered bone organs (hTEBOs). Tumors were harvested 5 weeks post-implantation to determine the expression of the previously described OS markers ezrin, periostin, VEGF, HIF1α and HIF2α. Representation of these proteins was analyzed in two different OS patient cohorts. Ezrin was downregulated in OS in hTEBOs with rhBMP-7, whereas HIF2α was significantly upregulated in comparison to hTEBOs without rhBMP-7. The expression of periostin, VEGF and HIF1α did not differ significantly between both groups. HIF2α was consistently present in OS patients and dependent on tumor site and clinical stage. OS patients post-chemotherapy had suppressed levels of HIF2α. In conclusion, we demonstrated the overall expression of OS-related factors in a preclinical model, which is based on a humanized bone organ. Our preclinical research results and analysis of two comprehensive patient cohorts imply that HIF2α is a potential prognostic marker and/or therapeutic target. STATEMENT OF SIGNIFICANCE: This study demonstrates the clinical relevance of the humanized organ bone microenvironment in osteosarcoma research and validates the expression of tumor markers, especially HIF2α. The convergence of clinically proven bone engineering concepts for the development of humanized mice models is a new starting point for investigations of OS-related marker expression. The validation and first data set in such a model let one conclude that further clinical studies on the role of HIF2α as a prognostic marker and its potential as therapeutic target is a condition sine qua non.

A 3D tumor microenvironment regulates cell proliferation, peritoneal growth and expression patterns.

Peritoneal invasion through the mesothelial cell layer is a hallmark of ovarian cancer metastasis. Using tissue engineering technologies, we recreated an ovarian tumor microenvironment replicating this aspect of disease progression. Ovarian cancer cell-laden hydrogels were combined with mesothelial cell-layered melt electrospun written scaffolds and characterized with proliferation and transcriptomic analyses and used as intraperitoneal xenografts. Here we show increased cancer cell proliferation in these 3D co-cultures, which we validated using patient-derived cells and linked to peritoneal tumor growth in vivo. Transcriptome-wide expression analysis identified IGFBP7, PTGS2, VEGFC and FGF2 as bidirectional factors deregulated in 3D co-cultures compared to 3D mono-cultures, which we confirmed by immunohistochemistry of xenograft and patient-derived tumor tissues and correlated with overall and progression-free survival. These factors were further increased upon expression of kallikrein-related proteases. This clinically predictive model allows us to mimic the complexity and processes of the metastatic disease that may lead to therapies that protect from peritoneal invasion or delay the development of metastasis.