Rheological Analysis and Evaluation of Measurement Techniques for Curing Poly(Methyl Methacrylate) Bone Cement in Vertebroplasty.

Vertebroplasty is a minimally invasive surgical procedure used to treat vertebral fractures, which conventionally involves injecting poly(methyl methacrylate) (PMMA) bone cement into the fractured vertebra. A common risk associated with vertebroplasty is cement leaking out of the vertebra during the injection, which may occur due to a lack of understanding of the complex flow behavior. Therefore, experiments to quantify the cement's flow properties are necessary for understanding and proper handling of the bone cement. In this study, we aimed to characterize the behavior of PMMA bone cement in its curing stages to obtain parameters that govern the flow behavior during injection. We used rotational and oscillatory rheometry for our measurements, as well as a custom-made injector setup that replicated a typical vertebroplasty setting. Our results showed that the complex viscoelastic behavior of bone cement is significantly affected by deformations and temperature. We found that the results from rotational tests, often used for characterizing the bone cement, are susceptible to measurement artifacts caused by wall slip and "ridge"-like formations in the test sample. We also found the Cox-Merz rule to be conditionally valid, which affects the use of oscillatory tests to obtain the shear-thinning characteristics of bone cement. Our findings identify important differences in the measured flow behavior of PMMA bone cement when assessed by different rheological methods, an understanding that is crucial for its risk-free usage in downstream medical applications.

Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model.

Background: Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model. Methods: Ten skeletally mature sheep (4-5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1-L2, L2-L3, and L3-L4 lumbar IVDs. L4-L5 IVDs were Intact controls. IVD injury levels received: (1) no treatment (Injury), (2) poly (ethylene glycol) diacrylate (PEGDA), (3) genipin-crosslinked fibrin (FibGen), (4) carboxymethylcellulose-methylcellulose (C-MC), or (5) C-MC and FibGen (FibGen + C-MC). Animals healed for 12 weeks, then IVDs were assessed using computed tomography (CT), magnetic resonance (MR) imaging, and histopathology. Results: All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. All repairs had similar disc height loss and Pfirrmann grade as Injury IVDs. Adhesive AF sealants (i.e., PEGDA and FibGen) did not herniate, although repair caused local endplate (EP) changes and inflammation. NP repair biomaterials (i.e., C-MC) and combination repair (i.e., FibGen + C-MC) exhibited lower levels of degeneration, less EP damage, and less severe inflammation; however, C-MC showed signs of herniation via biomaterial expulsion. Conclusions: All repair IVDs were noninferior to Injury IVDs by IVD height loss and Pfirrmann grade. C-MC and FibGen + C-MC IVDs had the best outcomes, and may be appropriate for enhancement with bioactive factors (e.g., cells, growth factors, and miRNAs). Such bioactive factors appear to be necessary to prevent injury-induced IVD degeneration. Application of AF sealants alone (i.e., PEGDA and FibGen) resulted in EP damage and inflammation, particularly for PEGDA IVDs, suggesting further material refinements are needed.

First Tarsometatarsal Joint Fusion in Foot-A Biomechanical Human Anatomical Specimen Analysis with Use of Low-Profile Nitinol Staples Acting as Continuous Compression Implants.

Background and Objectives: The aim of this study was to investigate under dynamic loading the potential biomechanical benefit of simulated first tarsometatarsal (TMT-1) fusion with low-profile superelastic nitinol staples used as continuous compression implants (CCIs) in two different configurations in comparison to crossed screws and locked plating in a human anatomical model. Materials and Methods: Thirty-two paired human anatomical lower legs were randomized to four groups for TMT-1 treatment via: (1) crossed-screws fixation with two 4.0 mm fully threaded lag screws; (2) plate-and-screw fixation with a 4.0 mm standard fully threaded cortex screw, inserted axially in lag fashion, and a 6-hole TMT-1 Variable-Angle (VA) Fusion Plate 2.4/2.7; (3) CCI fixation with two two-leg staples placed orthogonally to each other; (4) CCI fixation with one two-leg staple and one four-leg staple placed orthogonally to each other. Each specimen was biomechanically tested simulating forefoot weightbearing on the toes and metatarsals. The testing was performed at 35-37 °C under progressively increasing cyclic axial loading until construct failure, accompanied by motion tracking capturing movements in the joints. Results: Combined adduction and dorsiflexion movement of the TMT-1 joint in unloaded foot condition was associated with no significant differences among all pairs of groups (p ≥ 0.128). In contrast, the amplitude of this movement between unloaded and loaded foot conditions within each cycle was significantly bigger for the two CCI fixation techniques compared to both crossed-screws and plate-and-screw techniques (p ≤ 0.041). No significant differences were detected between the two CCI fixation techniques, as well as between the crossed-screws and plate-and-screw techniques (p ≥ 0.493) for this parameter of interest. Furthermore, displacements at the dorsal and plantar aspects of the TMT-1 joint in unloaded foot condition, together with their amplitudes, did not differ significantly among all pairs of groups (p ≥ 0.224). Conclusions: The low-profile superelastic nitinol staples demonstrate comparable biomechanical performance to established crossed-screws and plate-and-screw techniques applied for fusion of the first tarsometatarsal joint.

A continuum mechanical porous media model for vertebroplasty: Numerical simulations and experimental validation.

The outcome of vertebroplasty is hard to predict due to its dependence on complex factors like bone cement and marrow rheologies. Cement leakage could occur if the procedure is done incorrectly, potentially causing adverse complications. A reliable simulation could predict the patient-specific outcome preoperatively and avoid the risk of cement leakage. Therefore, the aim of this work was to introduce a computationally feasible and experimentally validated model for simulating vertebroplasty. The developed model is a multiphase continuum-mechanical macro-scale model based on the Theory of Porous Media. The related governing equations were discretized using a combined finite element-finite volume approach by the so-called Box discretization. Three different rheological upscaling methods were used to compare and determine the most suitable approach for this application. For validation, a benchmark experiment was set up and simulated using the model. The influence of bone marrow and parameters like permeability, porosity, etc., was investigated to study the effect of varying conditions on vertebroplasty. The presented model could realistically simulate the injection of bone cement in porous materials when used with the correct rheological upscaling models, of which the semi-analytical averaging of the viscosity gave the best results. The marrow viscosity is identified as the crucial reference to categorize bone cements as 'high- 'or 'low-' viscosity in the context of vertebroplasty. It is confirmed that a cement with higher viscosity than the marrow ensures stable development of the injection and a proper cement interdigitation inside the vertebra.

Statistical Morphology and Fragment Mapping of Complex Proximal Humeral Fractures.

Background and Objectives: Proximal humerus fractures (PHFs) are common in the elderly, but the treatment results are often poor. A clear understanding of fracture morphology and distribution of cortical bone loss is important for improved surgical decision making, operative considerations, and new implant designs. The aim of this study was to develop a 3D segmentation fracture mapping technique to create a statistical description of the spatial pattern and cortical bone loss of complex PHFs. Materials and Methods: Fifty clinical computed tomography (CT) scans of complex PHFs and their contralateral intact shoulders were collected. In-house software was developed for semi-automated segmentation and fracture line detection and was combined with manual fracture reduction to the contralateral template in a commercial software. A statistical mean model of these cases was built and used to describe probability maps of the fracture lines and cortical fragments. Results: The fracture lines predominantly passed through the surgical neck and between the tuberosities and tendon insertions. The superior aspects of the tuberosities were constant fragments where comminution was less likely. Some fracture lines passed through the bicipital sulcus, but predominantly at its edges and curving around the tuberosities proximally and distally. Conclusions: A comprehensive and systematic approach was developed for processing clinical CT images of complex fractures into fracture morphology and fragment probability maps and applied on PHFs. This information creates an important basis for better understanding of fracture morphology that could be utilized in future studies for surgical training and implant design.

Anatomical analysis of different helical plate designs for proximal humeral shaft fracture fixation.

OBJECTIVES: Helical plates are preferably used for proximal humeral shaft fracture fixation and potentially avoid radial nerve irritation. AIMS: Safety of applying four different long plate designs (straight, 45°-, 90°-helical and ALPS) with MIPO technique as well as assessment and comparison of their distances to adjacent anatomical structures. METHODS: MIPO was performed in 16 human cadaveric humeri using either a straight (group 1), a 45°-helical (group 2), a 90°-helical (group 3) plate, or an ALPS (group 4). Applying CT angiography, distances between brachial arteries and plates were evaluated. All specimens were dissected and distances to the axillary, radial and musculocutaneous nerve were evaluated. RESULTS: No specimens demonstrated injuries of the anatomical structures at risk after MIPO with all investigated plate designs. Closest overall distance (mean (range); mm) between each plate and the radial nerve was 1 (1-3) in group 1, 7 (2-11) in group 2, 14 (7-25) in group 3 and 6 (3-8) in group 4. It was significantly bigger in group 3 and significantly smaller in group 1 compared to all other groups, p < 0.001. Closest overall distance between each plate and the musculocutaneous nerve was 16 (8-28) in group 1, 11 (7-18) in group 2, 3 (2-4) in group 3 and 6 (3-8) in group 4. It was significantly bigger in group 1 and significantly smaller in group 3 compared to all other groups, p < 0.001. CONCLUSIONS: MIPO with 45°- and 90°-helical plates as well as with ALPS is safely feasible and demonstrates significantly bigger distances to the radial nerve compared to straight plates. However, the distances remain small and attention must be paid to the musculocutaneous nerve and the brachial artery when MIPO is applied using ALPS, 45°- and 90°-helical implants.

Venous injection of a triphasic calcium-based implant in a sheep model of pulmonary embolism demonstrates minimal acute systemic effects.

PURPOSE: Implant leakage is the most common complication of vertebral augmentation. Alternative injectable materials must demonstrate intravascular safety comparable to or better than polymethyl methacrylate (PMMA). This study assessed the systemic effects of a triphasic calcium-based implant or PMMA injected directly into the femoral vein in a large animal model designed to mimic severe intravascular implant leakage. METHODS: Six skeletally mature female sheep were randomly assigned (n = 3) to either the PMMA or the triphasic implant (AGN1, composition: calcium sulfate, ß-tricalcium phosphate, brushite) treatment group. Femoral veins of each sheep were directly injected with 0.5 mL of implant material to mimic leakage volumes reported during PMMA vertebroplasty. To compare acute systemic effects of the materials, cardiovascular parameters, laboratory coagulation markers, and calcium and sulfate serum levels were monitored for 60 min after implant injection. Thrombotic and embolic events were evaluated by radiologic imaging, necropsy, and histopathology. RESULTS: Heart rate, systemic arterial blood pressure, arterial oxygenation, arterial carbon dioxide content, and coagulation markers remained within physiological range after either AGN1 or PMMA injection. No blood flow interruption in the larger pulmonary vessels was observed in either group. Lung histopathology revealed that the severity of thrombotic changes after AGN1 injection was minimal to slight, while changes after PMMA injection were minimal to massive. CONCLUSION: Acute systemic effects of intravascular AGN1 appeared to be comparable to or less than that of intravascular PMMA. Furthermore, in this preliminary study, the severity and incidence of pulmonary histological changes were lower for AGN1 compared to PMMA.

Comparison and optimization of sheep in vivo intervertebral disc injury model.

Background: The current standard of care for intervertebral disc (IVD) herniation, surgical discectomy, does not repair annulus fibrosus (AF) defects, which is partly due to the lack of effective methods to do so and is why new repair strategies are widely investigated and tested preclinically. There is a need to develop a standardized IVD injury model in large animals to enable comparison and interpretation across preclinical study results. The purpose of this study was to compare in vivo IVD injury models in sheep to determine which annulus fibrosus (AF) defect type combined with partial nucleus pulposus (NP) removal would better mimic degenerative human spinal pathologies. Methods: Six skeletally mature sheep were randomly assigned to one of the two observation periods (1 and 3 months) and underwent creation of 3 different AF defect types (slit, cruciate, and box-cut AF defects) in conjunction with 0.1 g NP removal in three lumbar levels using a lateral retroperitoneal surgical approach. The spine was monitored by clinical CT scans pre- and postoperatively, at 2 weeks and euthanasia, and by magnetic resonance imaging (MRI) and histology after euthanasia to determine the severity of degeneration (disc height loss, Pfirrmann grading, semiquantitative histopathology grading). Results: All AF defects led to significant degenerative changes detectable on CT and MR images, produced bulging of disc tissue without disc herniation and led to degenerative and inflammatory histopathological changes. However, AF defects were not equal in terms of disc height loss at 3 months postoperatively; the cruciate and box-cut AF defects showed significantly decreased disc height compared to their preoperative height, with the box-cut defect creating the greatest disc height loss, while the slit AF defect showed restoration of normal preoperative disc height. Conclusions: The tested IVD injury models do not all generate comparable disc degeneration but can be considered suitable IVD injury models to investigate new treatments. Results of the current study clearly indicate that slit AF defect should be avoided if disc height is used as one of the main outcomes; additional confirmatory studies may be warranted to generalize this finding.

Continuous Implant Load Monitoring to Assess Bone Healing Status-Evidence from Animal Testing.

Background and Objectives: Fracture healing is currently assessed through qualitative evaluation of radiographic images, which is highly subjective in nature. Radiographs can only provide snapshots in time, which are limited due to logistics and radiation exposure. We recently proposed assessing the bone healing status through continuous monitoring of the implant load, utilizing an implanted sensor system, the Fracture Monitor. The device telemetrically transmits statistically derived implant parameters via the patient's mobile phone to assist physicians in diagnostics and treatment decision-making. This preclinical study aims to systematically investigate the device safety and performance in an animal setting. Materials and Methods: Mid-shaft tibial osteotomies of different sizes (0.6-30 mm) were created in eleven Swiss mountain sheep. The bones were stabilized with either a conventional Titanium or stainless-steel locking plate equipped with a Fracture Monitor. Data were continuously collected over the device's lifetime. Conventional radiographs and clinical CT scans were taken longitudinally over the study period. The radiographs were systematically scored and CTs were evaluated for normalized bone volume in the defect. The animals were euthanized after 9 months. The sensor output was correlated with the radiologic parameters. Tissue samples from the device location were histologically examined. Results: The sensors functioned autonomously for 6.5-8.4 months until energy depletion. No macroscopic or microscopic adverse effects from device implantation were observed. The relative implant loads at 4 and 8 weeks post-operation correlated significantly with the radiographic scores and with the normalized bone volume metric. Conclusions: Continuous implant load monitoring appears as a relevant approach to support and objectify fracture healing assessments and carries a strong potential to enable patient-tailored rehabilitation in the future.

Interleukin-1 receptor antagonist enhances the therapeutic efficacy of a low dose of rhBMP-2 in a weight-bearing rat femoral defect model.

In the clinical treatment of fractures, rhBMP-2 administration is associated with a well-established profile of side-effects, including osteolysis and ectopic bone formation, which are driven by pro-inflammatory processes triggered by the use of high doses. Immunomodulatory strategies could minimize the incidence of side-effects by enabling the use of lower, and safer, rhBMP-2 doses. This study investigated whether interleukin-1 receptor antagonist (IL-1Ra) can enhance the therapeutic efficacy of a low dose of rhBMP-2 in a weight-bearing femoral fracture healing model. Exogenous IL-1Ra, in combination with rhBMP-2, was delivered using a collagen-hydroxyapatite scaffold (CHA) to attenuate IL-1ß produced in response to fracture. Femoral defects were treated with CHA scaffolds alone, or loaded with IL-1Ra (2.5 µg), rhBMP-2 (1 µg), IL-1Ra (2.5 µg) in combination with rhBMP-2 (1 µg). Bone healing was assessed over 14 weeks in comparison to control groups, empty defect, and a higher dose of rhBMP-2 (5 µg), which were recently demonstrated to lead to non-union, and successful bridging of the defect, respectively. The combination of IL-1Ra and rhBMP-2 led to significantly faster early bone formation, at both week 4 and 6, compared to a low dose of rhBMP-2 alone. By 14 weeks, the combination of IL-1Ra and a rhBMP-2 promoted full bridging of femurs, which were 3-fold more mechanically reliable compared to the femurs treated with a low dose of rhBMP-2 alone. Taken together, this study demonstrates that IL-1Ra can significantly enhance femoral bone healing when used in combination with a low dose of rhBMP-2. STATEMENT OF SIGNIFICANCE: Enabling the use of lower and safer doses of rhBMP-2, a potent inducer of bone formation, is of clinical relevance in orthopaedic medicine. In this study, the immunomodulatory interleukin-1 receptor antagonist (IL-1Ra) was investigated for its capacity to enhance the therapeutic efficacy of rhBMP-2 when used at lower doses in a weight-bearing femoral fracture healing model. The combination of IL-1Ra and rhBMP-2 led to significantly faster early bone formation, and resulted in more mechanically reliable healed femurs, compared to a low dose of rhBMP-2 alone. This demonstrates for the first time in a rat long bone healing model that IL-1Ra can significantly enhance bone healing when used in combination with a low dose of rhBMP-2.

Is there a correlation between pelvic incidence and orientation of the acetabulum? An analysis based on a three-dimensional statistical model of the pelvic ring.

The pelvic ring is a complex anatomical structure building up the connection between the trunk and the legs. Whilst there is a broad discussion in the literature about the dynamic interaction between spine, pelvis and the hip joints, there is still little information about the relation and interaction of the constant pelvic parameters. Based on a three-dimensional (3D) statistical model consisting of 150 uninjured and bony healthy pelves (100 Europeans, 50 Japanese; 81 males, 69 females; average age 74.3 years ± 17.5 years) an evaluation of pelvic incidence (PI) and acetabular orientation in anteversion and inclination was performed and potential correlations of these intraindividual constant parameters were investigated. Pelvic incidence is defined as the angle between the perpendicular to the sacral plate at its midpoint and the line connecting this point to the middle axis of the femoral heads. Acetabular anteversion is defined as the angle between the perpendicular to the best-fit plane on the acetabular rim and the coronal plane measured in strict lateral view. Acetabular inclination is defined as the angle between the perpendicular to the best-fit plane on the acetabular rim and the sagittal plane in strict frontal view. Data were further analysed with regard to different subgroup's age, sex and ethnicity. A positive correlation between PI and acetabular anteversion could be demonstrated. Further, PI and also the acetabular parameters anteversion and inclination were found to be significantly higher in the European individuals than in the Asian. The results of the present study demonstrate a relation between the anatomical configuration of the constant pelvic parameters building up the connection points to the next proximal respectively caudal skeleton section. The findings might lead to more comprehensive treatment strategies in case of trauma or degenerative pathologies of the pelvis in the future.

Effect of weightbearing and foot positioning on 3D distal tibiofibular joint parameters.

The aim of this study was to investigate the effect of different loading scenarios and foot positions on the configuration of the distal tibiofibular joint (DTFJ). Fourteen paired human cadaveric lower legs were mounted in a loading frame. Computed tomography scans were obtained in unloaded state (75 N) and single-leg loaded stand (700 N) of each specimen in five foot positions: neutral, 15° external rotation, 15° internal rotation, 20° dorsiflexion, and 20° plantarflexion. An automated three-dimensional measurement protocol was used to assess clear space (diastasis), translational angle (rotation), and vertical offset (fibular shortening) in each foot position and loading condition. Foot positioning had a significant effect on DTFJ configuration. Largest effects were related to clear space increase by 0.46 mm (SD 0.21 mm) in loaded dorsal flexion and translation angle of 2.36° (SD 1.03°) in loaded external rotation, both versus loaded neutral position. Loading had no effect on clear space and vertical offset in any position. Translation angle was significantly influenced under loading by - 0.81° (SD 0.69°) in internal rotation only. Foot positioning noticeably influences the measurements when evaluating DTFJ configuration. Loading seems to have no relevant effect on native ankles in neutral position.

Percutaneous fixation of intraarticular joint-depression calcaneal fractures with different screw configurations - a biomechanical human cadaveric analysis.

PURPOSE: The aim of this study was to assess the biomechanical performance of different screw configurations for fixation of Sanders type II B joint-depression calcaneal fractures. METHODS: Fifteen human cadaveric lower limbs were amputated and Sanders II B fractures were simulated. The specimens were randomized to three groups for fixation with different screw configurations. The calcanei in Group 1 were treated with two parallel longitudinal screws, entering superiorly the Achilles tendon insertion, and two screws fixing the intraarticular posterior facet fracture line. In Group 2 two screws entered the tuberosity inferiorly to the Achilles tendon insertion and two transverse screws fixed the posterior facet. In Group 3 two screws were inserted along the bone axis, one transverse screw fixed the posterior facet and one oblique screw was inserted from the posteroplantar part of the tuberosity supporting the posterolateral part of the posterior facet. All specimens were biomechanically tested to failure under progressively increasing cyclic loading. RESULTS: Initial stiffness did not differ significantly between the groups, P = 0.152. Cycles to 2 mm plantar movement were significantly higher in both Group 1 (15,847 ± 5250) and Group 3 (13,323 ± 4363) compared with Group 2 (4875 ± 3480), P ≤ 0.048. No intraarticular displacement was observed in any group during testing. CONCLUSIONS: From a biomechanical perspective, posterior facet support by means of buttress or superiorly inserted longitudinal screws results in less plantar movement between the calcaneal tuberosity and the anterior fragments. Inferiorly inserted longitudinal screws are associated with bigger interfragmentary movements.

Anatomical analysis of different helical plate designs for distal femoral fracture fixation.

PURPOSE: Helical plates potentially avoid the medial neurovascular structures of the thigh. Two implant designs for additional medial 90° helical plate in double plate constructs for geriatric patients and 180° helical plate for single plating in young patients are potential alternatives to widely used standard straight plates. AIMS: (1) assess the distances to adjacent anatomical structures being at risk when applying medial 90° and 180° helical plates with MIPO technique to the femur, (2) compare these distances with medial straight plates, and (3) correlate measurements performed during surgical dissection with CT angiography. METHODS: MIPO was performed in ten human cadaveric femoral pairs using either a 90° helical 14-hole LCP (Group 1) or a 180° helical 15-hole LCP-DF (Group 2). Using CT angiography, distances between femoral arteries and plates as well as distances between plates and perforating vessels were evaluated. Following, specimens were dissected and distances determined again. All plates were removed and measurements were repeated with straight medial plates (Group 3). RESULTS: Overall closest distances between plates and femoral arteries were 14.5 mm (11-19 mm) in Group 1, 21.6 mm (15-24 mm) in Group 2 and 6.5 mm (5-8 mm) in Group 3, with significant differences between Group 3 and both other groups (p < 0.001). Distances to the nearest perforating vessels were 22.4 mm (15-30 mm) in Group 1 and 1.2 mm (1-2 mm) in Group 2. Measurement techniques (visual after surgical disection and CT angiography) demonstrated a strong correlation (p < 0.010). CONCLUSIONS: Inserting 90° and 180° helical plates with MIPO technique is safe, however, attention must be paid to the medial neurovascular structures with 90° helical plates and to the proximal perforating vessels with 180° helical plates. Helical plates can avoid irritation of medial neurovascular structures - compared with straight plates - although care must be taken during their distal insertion. Measurements during surgical dissection correlate with CT angiography.

Influence of screw head diameter on ex vivo fixation of equine lateral condylar fractures with 5.5 mm cortical screws.

OBJECTIVE: To determine the influence of screw head diameter on equine condylar fracture fixation with 5.5 mm cortical screws. STUDY DESIGN: Ex vivo, biomechanical study, blinded, matched-pair design. SAMPLE POPULATION: Fifteen pairs of equine third metacarpal (MC3) bones. METHODS: Lateral condylar fractures were simulated by parasagittal osteotomies and repaired pairwise by 2 × 5.5 mm cortical screws of 8 mm (standard) or 10 mm (modified) head diameter. Interfragmentary compression at maximum screw insertion torque was measured. The instrumented specimens were pairwise stratified for biomechanical testing under the following modalities (n = 5): (1) screw insertion torque to failure, (2) quasi-static axial load to failure, and (3) cyclic axial load to 2 mm displacement followed by failure. Tests (1) and (2) were analyzed for yield, maximum, and failure torque/angle and load/displacement, respectively. Number of cycles to 2 mm displacement and failure was assessed from test (3). RESULTS: Maximum insertion torque was greater, and failure angle smaller, when constructs repaired with modified screws were tested (8.1 ± 0.5 vs. 7.4 ± 0.5 Nm; P = .0047 and 550 ± 104 vs. 1130 ± 230; P = .008). Axial yield (7118 ± 707 vs. 5740 ± 2267 N; P = .043) and failure load (12 347 ± 3359 vs. 8695 ± 2277 N; P = .043) were greater for specimens repaired with modified screws. No difference was detected between constructs in the number of cycles to 2 mm displacement. CONCLUSION: Condylar MC3 osteotomies repaired with modified 5.5 mm cortical screws sustained greater maximal hand torque insertion, smaller insertion failure angle and 1.4 fold greater quasi-static failure forces than constructs repaired with standard 5.5 mm screws. CLINICAL SIGNIFICANCE: Use of modified screws with larger heads may improve the fixation of condylar fractures in horses. These results provide evidence to justify clinical evaluation in horses undergoing fracture repair.

Local bone quality measure and construct failure prediction: a biomechanical study on distal femur fractures.

INTRODUCTION: The aim of this investigation was to better understand the differences in local bone quality at the distal femur and their correlation with biomechanical construct failure, with the intention to identify regions of importance to optimize implant anchorage. MATERIALS AND METHODS: Seven fresh-frozen female femurs underwent high-resolution peripheral quantitative computed tomography (HR-pQCT) to determine bone mineral density (BMD) within three different regions of interest (distal, intermedium, and proximal) at the distal femur. In addition, local bone quality was assessed by measuring the peak torque necessary to break out the trabecular bone along each separate hole of a locking compression plate (LCP) during its instrumentation. Finally, biomechanical testing was performed using cyclic axial loading until failure in an AO/OTA 33 A3 fracture model. RESULTS: Local BMD was highest in the distal region. This was confirmed by the measurement of local bone quality using DensiProbe™. The most distal holes represented locations with the highest breakaway torque resistance, with the holes on the posterior side of the plate indicating higher values than those on its anterior side. We demonstrated strong correlation between the cycles to failure and local bone strength (measured with DensiProbe™) in the most distal posterior screw hole, having the highest peak torque. CONCLUSION: The local bone quality at the distal femur indicates that in plated distal femur fractures the distal posterior screw holes seem to be the key ones and should be occupied. Measurement of the local bone strength with DensiProbe™ is one possibility to determine the risk of construct failure, therefore, thresholds need to be defined.

Leave it or fix it? How fixation of a small posterior malleolar fragment neutralizes rotational forces in trimalleolar fractures.

INTRODUCTION: This study investigated the effects of a small posterior malleolar fragment (PMF), containing less than 25% articular surface area, on ankle joint stability via computed tomography (CT) scanning under full weight bearing in a human cadaveric ankle fracture model. MATERIALS AND METHODS: A trimalleolar fracture with a PMF of less than 25% articular surface area was created in 6 pairs of fresh-frozen human cadaveric lower legs. The specimens were randomized into 2 groups stabilized by internal fixation including a positioning screw for syndesmotic reconstruction. In Group I the PMF was addressed by direct screw osteosynthesis, whereas in Group II the fragment was not fixed. Six predefined distances within the ankle were measured under axial loading. CT scans of each specimen were performed in intact and fixated states in neutral position, dorsiflexion and plantar-flexion of the ankle. RESULTS: In plantar-flexion, significant differences were detected between the groups with regard to rotational instability. Group II demonstrated a significantly increased inward rotation of the fibula compared with Group I. No significant differences were detected between the groups for each one of the measured distances in any of the three foot positions. CONCLUSIONS: Additional reduction and fixation of a small PMF seems to neutralize rotational forces in the ankle more effectively than a sole syndesmotic screw. Clinically, this becomes relevant in certain phases of the gait cycle. Direct screw osteosynthesis of a small PMF stabilizes the ankle more effectively than a positioning screw.

Biomechanical analysis of recently released cephalomedullary nails for trochanteric femoral fracture fixation in a human cadaveric model.

BACKGROUND: Recently, two novel concepts for intramedullary nailing of trochanteric fractures using a helical blade or interlocking dual screws have demonstrated advantages as compared to standard single-screw systems. However, these two concepts have not been subjected to a direct biomechanical comparison so far. The aims of this study were to investigate in a human cadaveric model with low bone quality (1) the biomechanical competence of nailing with the use of a helical blade versus interlocking screws, and (2) the effect of cement augmentation on the fixation strength of the helical blade. METHODS: Twelve osteoporotic and osteopenic human cadaveric femoral pairs were assigned for pairwise implantation using either a short TFN-ADVANCED Proximal Femoral Nailing System (TFNA) with a helical blade head element or a short TRIGEN INTERTAN Intertrochanteric Antegrade Nail (InterTAN) with interlocking screws. Six osteoporotic femora, implanted with TFNA, were augmented with bone cement. Four groups were created: group 1 (TFNA) paired with group 2 (InterTAN), both consisting of osteopenic specimens, and group 3 (TFNA augmented) paired with group 4 (InterTAN), both consisting of osteoporotic specimens. An unstable trochanteric AO/OTA 31-A2.2 fracture was simulated and all specimens were tested until failure under progressively increasing cyclic loading. RESULTS: Stiffness in group 3 was significantly higher versus group 4, p = 0.03. Varus (°) and femoral head rotation around the femoral neck axis (°) after 10,000 cycles were 1.9 ± 1.0/0.3 ± 0.2 in group 1, 2.2 ± 0.7/0.7 ± 0.4 in group 2, 1.5 ± 1.3/0.3 ± 0.2 in group 3 and 3.5 ± 2.8/0.9 ± 0.6 in group 4, being significantly different between groups 3 and 4, p = 0.04. Cycles to failure and failure load (N) at 5° varus or 10° femoral head rotation around the neck axis in groups 1-4 were 21,428 ± 6020/1571.4 ± 301.0, 20,611 ± 7453/1530.6 ± 372.7, 21,739 ± 4248/1587.0 ± 212.4 and 18,622 ± 6733/1431.1 ± 336.7, being significantly different between groups 3 and 4, p = 0.04. CONCLUSIONS: Nailing of trochanteric femoral fractures with use of helical blades is comparable to interlocking dual screws fixation in femoral head fragments with low bone quality. Bone cement augmentation of helical blades provides significantly greater fixation strength compared to interlocking screws constructs.

Butyrate Inhibits Osteoclast Activity In Vitro and Regulates Systemic Inflammation and Bone Healing in a Murine Osteotomy Model Compared to Antibiotic-Treated Mice.

Short-chain fatty acids (SCFAs) produced by the gut microbiota have previously been demonstrated to play a role in numerous chronic inflammatory diseases and to be key mediators in the gut-bone signaling axis. However, the role of SCFAs in bone fracture healing and its impact on systemic inflammation during the regeneration process has not been extensively investigated yet. The aim of this study was to first determine the effects of the SCFA butyrate on key cells involved in fracture healing in vitro, namely, osteoclasts and mesenchymal stromal cells (MSCs), and second, to assess if butyrate supplementation or antibiotic therapy impacts bone healing, systemic immune status, and inflammation levels in a murine osteotomy model. Butyrate significantly reduced osteoclast formation and resorption activity in a dose-dependent manner and displayed a trend for increased calcium deposits in MSC cultures. Numerous genes associated with osteoclast differentiation were differentially expressed in osteoclast precursor cells upon butyrate exposure. In vivo, antibiotic-treated mice showed reduced SCFA levels in the cecum, as well as a distinct gut microbiome composition. Furthermore, circulating proinflammatory TNFα, IL-17a, and IL-17f levels, and bone preserving osteoprotegerin (OPG), were increased in antibiotic-treated mice compared to controls. Antibiotic-treated mice also displayed a trend towards delayed bone healing as revealed by reduced mineral apposition at the defect site and higher circulating levels of the bone turnover marker PINP. Butyrate supplementation resulted in a lower abundance of monocyte/macrophages in the bone marrow, as well as reduced circulating proinflammatory IL-6 levels compared to antibiotic- and control-treated mice. In conclusion, this study supports our hypothesis that SCFAs, in particular butyrate, are important contributors to successful bone healing by modulating key cells involved in fracture healing as well as systemic inflammation and immune responses.

An Enzybiotic Regimen for the Treatment of Methicillin-Resistant Staphylococcus aureus Orthopaedic Device-Related Infection.

Orthopaedic device-related infection (ODRI) presents a significant challenge to the field of orthopaedic and trauma surgery. Despite extensive treatment involving surgical debridement and prolonged antibiotic therapy, outcomes remain poor. This is largely due to the unique abilities of Staphylococcus aureus, the most common causative agent of ODRI, to establish and protect itself within the host by forming biofilms on implanted devices and staphylococcal abscess communities (SACs). There is a need for novel antimicrobials that can readily target such features. Enzybiotics are a class of antimicrobial enzymes derived from bacteria and bacteriophages, which function by enzymatically degrading bacterial polymers essential to bacterial survival or biofilm formation. Here, we apply an enzybiotic-based combination regimen to a set of in vitro models as well as in a murine ODRI model to evaluate their usefulness in eradicating established S. aureus infection, compared to classical antibiotics. We show that two chimeric endolysins previously selected for their functional efficacy in human serum in combination with a polysaccharide depolymerase reduce bacterial CFU numbers 10,000-fold in a peg model and in an implant model of biofilm. The enzyme combination also completely eradicates S. aureus in a SAC in vitro model where classical antibiotics are ineffective. In an in vivo ODRI model in mice, the antibiofilm effects of this enzyme regimen are further enhanced when combined with a classical gentamicin/vancomycin treatment. In a mouse model of methicillin-resistant S. aureus (MRSA) ODRI following a fracture repair, a combined local enzybiotic/antibiotic treatment regimen showed a significant CFU reduction in the device and the surrounding soft tissue, as well as significant prevention of weight loss. These outcomes were superior to treatment with antibiotics alone. Overall, this study demonstrates that the addition of enzybiotics, which are distinguished by their extremely rapid killing efficacy and antibiofilm activities, can enhance the treatment of severe MRSA ODRI.