Patient-specific finite element modeling for fracture risk prediction in a canine model of osteosarcoma.

Background: In cancer patients with bone tumors, pathological fractures are a major concern. Making treatment decision for these patients requires an evaluation of fracture risk, which is currently based on semi-qualitative criteria that lack patient-specificity. Because of this, there exists a need for quantitative fracture risk prediction tailored to the patient's individual bone geometry. To address this need, this study aims to develop and validate a finite element (FE) technique that can be used to create patient-specific models and more accurately identify fracture risk. Model validation was performed using canine radii. Methods: Radii were harvested from eight canines euthanized for reasons unrelated to the study. A semicircular osteotomy was made in the distal portion of each bone to simulate tumor lysis. Samples underwent computed tomography (CT) scanning and were randomly assigned to loading groups for destructive mechanical testing. Three samples were tested in torsion, three in cantilever bending, and two in compression. FE models were created for each bone from the corresponding CT scan to replicate patient-specific geometry. Material properties were based on equations relating scan properties to elastic modulus. Boundary conditions and loads were added to the models based on the sample's treatment group. Stiffness and strain data were collected from both the mechanical testing and FE simulation, and yield load predictions were made based on maximum principal strain. Experimental and computational results were compared using a linear regression. Results: The FE models were most accurate in predicting stiffness, followed by strain, with yield load having the lowest accuracy. Linear regressions resulted in R2 values of 0.9335 for bending and compression and 0.8798 for torsion. Conclusions: The proposed FE technique is a valid method for predicting fracture in a canine model of osteosarcoma. This method could provide patient-specific, quantitative data to aid clinicians in decisions regarding surgical intervention for patients with bone tumors.

Novel 3D printed lattice structure titanium cages evaluated in an ovine model of interbody fusion.

Background: The use of intervertebral cages within the interbody fusion setting is ubiquitous. Synthetic cages are predominantly manufactured using materials such as Ti and PEEK. With the advent of additive manufacturing techniques, it is now possible to spatially vary complex 3D geometric features within interbody devices, enabling the devices to match the stiffness of native tissue and better promote bony integration. To date, the impact of surface porosity of additively manufactured Ti interbody cages on fusion outcomes has not been investigated. Thus, the objective of this work was to determine the effect of implant endplate surface and implant body architecture of additive manufactured lattice structure titanium interbody cages on bony fusion. Methods: Biomechanical, microcomputed tomography, static and dynamic histomorphometry, and histopathology analyses were performed on twelve functional spine units obtained from six sheep randomly allocated to body lattice or surface lattice groups. Results: Nondestructive kinematic testing, microcomputed tomography analysis, and histomorphometry analyses of the functional spine units revealed positive fusion outcomes in both groups. These data revealed similar results in both groups, with the exception of bone-in-contact analysis, which revealed significantly improved bone-in-contact values in the body lattice group compared to the surface lattice group. Conclusion: Both additively manufactured porous titanium cage designs resulted in increased fusion outcomes as compared to PEEK interbody cage designs as illustrated by the nondestructive kinematic motion testing, static and dynamic histomorphometry, microcomputed tomography, and histopathology analyses. While both cages provided for similar functional outcomes, these data suggest boney contact with an interbody cage may be impacted by the nature of implant porosity adjacent to the vertebral endplates.

Employing direct electromagnetic coupling to assess acute fracture healing: An ovine model assessment.

OBJECTIVES: This study explored the efficacy of collecting temporal fracture site compliance data via an advanced direct electromagnetic coupling (DEC) system equipped with a Vivaldi-type antenna, novel calibration technique, and multi-antenna setup (termed maDEC) as an approach to monitor acute fracture healing progress in a translational large animal model. The overarching goal of this approach was to provide insights into the acute healing dynamics, offering a promising avenue for optimizing fracture management strategies. METHODS: A sample of twelve sheep, subjected to ostectomies and intramedullary nail fixations, was divided into two groups, simulating normal and impaired healing scenarios. Sequential maDEC compliance or stiffness measurements and radiographs were taken from the surgery until euthanasia at four or eight weeks and were subsequently compared with post-sacrifice biomechanical, micro-CT, and histological findings. RESULTS: The results showed that the maDEC system offered straightforward quantification of fracture site compliance via a multiantenna array. Notably, the rate of change in the maDEC-measured bending stiffness significantly varied between normal and impaired healing groups during both the 4-week (p = 0.04) and 8-week (p = 0.02) periods. In contrast, radiographically derived mRUST healing measurements displayed no significant differences between the groups (p = 0.46). Moreover, the cumulative normalized stiffness maDEC data significantly correlated with post-sacrifice mechanical strength (r2 = 0.80, p < 0.001), micro-CT measurements of bone volume fraction (r2 = 0.60, p = 0.003), and density (r2 = 0.60, p = 0.003), and histomorphometric measurements of new bone area fraction (r2 = 0.61, p = 0.003) and new bone area (r2 = 0.60, p < 0.001). CONCLUSIONS: These data indicate that the enhanced maDEC system provides a non-invasive, accurate method to monitor fracture healing during the acute healing phase, showing distinct stiffness profiles between normal and impaired healing groups and offering critical insights into the healing process's progress and efficiency.

Strain-dependent stress relaxation behavior of healthy right ventricular free wall.

The increasing evidence of stress-strain hysteresis in large animal or human myocardium calls for extensive characterizations of the passive viscoelastic behavior of the myocardium. Several recent studies have investigated and modeled the viscoelasticity of the left ventricle while the right ventricle (RV) viscoelasticity remains poorly understood. Our goal was to characterize the biaxial viscoelastic behavior of RV free wall (RVFW) using two modeling approaches. We applied both quasi-linear viscoelastic (QLV) and nonlinear viscoelastic (NLV) theories to experimental stress relaxation data from healthy adult ovine. A three-term Prony series relaxation function combined with an Ogden strain energy density function was used in the QLV modeling, while a power-law formulation was adopted in the NLV approach. The ovine RVFW exhibited an anisotropic and strain-dependent viscoelastic behavior relative to anatomical coordinates, and the NLV model showed a higher capacity in predicting strain-dependent stress relaxation than the QLV model. From the QLV fitting, the relaxation term associated with the largest time constant played the dominant role in the overall relaxation behavior at most strains from early to late diastole, whereas the term associated with the smallest time constant was pronounced only at low strains at early diastole. From the NLV fitting, the parameters showed a nonlinear dependence on the strain. Overall, our study characterized the anisotropic, nonlinear viscoelasticity to capture the elastic and viscous resistances of the RVFW during diastole. These findings deepen our understanding of RV myocardium dynamic mechanical properties. STATEMENT OF SIGNIFICANCE: Although significant progress has been made to understand the passive elastic behavior of the right ventricle free wall (RVFW), its viscoelastic behavior remains poorly understood. In this study, we originally applied both quasi-linear viscoelastic (QLV) and nonlinear viscoelastic (NLV) models to published experimental data from healthy ovine RVFW. Our results revealed an anisotropic and strain-dependent viscoelastic behavior of the RVFW. The parameters from the NLV fitting showed nonlinear relationships with the strain, and the NLV model showed a higher capacity in predicting strain-dependent stress relaxation than the QLV model. These findings characterize the anisotropic, nonlinear viscoelasticity of RVFW to fully capture the total (elastic and viscous) resistance that is critical to diastolic function.

Direct electromagnetic coupling to determine diagnostic bone fracture stiffness.

Background: Rapid prediction of adverse bone fracture healing outcome (e.g., nonunion and/or delayed union) is essential to advise adjunct therapies to reduce patient suffering and improving healing outcome. Radiographic diagnostic methods remain ineffective during early healing, resulting in average nonunion diagnosis times surpassing six months. To address this clinical deficit, we developed a novel diagnostic device to predict fracture healing outcome by noninvasive telemetric measurements of fracture bending stiffness. This study evaluated the hypothesis that our diagnostic antenna system is capable of accurately measuring temporal fracture healing stiffness, and advises the utility of this data for expedited prediction of healing outcomes during early (≤3 weeks) fracture recovery. Methods: Fracture repair was simulated, in reverse chronology, by progressively destabilizing cadaveric ovine metatarsals (n=8) stabilized via locking plate fixation. Bending stiffness of each fracture state were predicted using a novel direct electromagnetic coupling diagnostic system, and results were compared to values from material testing (MT) methods. While direct calculation of fracture stiffness in a simplistic cadaver model is possible, comparable analysis of the innumerable permutations of fracture and treatment type is not feasible. Thus, clinical feasibility of direct electromagnetic coupling was explored by parametric finite element (FE) analyses (n=1,632 simulations). Implant mechanics were simulated throughout the course of healing for cases with variations to fracture size, implant type, implant structure, and implant material. Results: For all fracture states, stiffness values predicted by the direct electromagnetic coupling system were not significantly different than those quantified by in vitro MT methods [P=0.587, P=0.985, P=0.975; for comparing intact, destabilized, and fully fractured (FF) states; respectively]. In comparable models, the total implant deflection reduction (from FF to intact states) was less than 10% different between direct electromagnetic coupling measurements (82.2 µm) and FE predictions (74.7 µm). For all treatment parameters, FE analyses predicted nonlinear reduction in bending induced implant midspan deflections for increasing callus stiffness. Conclusions: This technology demonstrates potential as a noninvasive clinical tool to accurately quantify healing fracture stiffness to augment and expedite healing outcome predictions made using radiographic imaging.

Vivaldi Antennas for Contactless Sensing of Implant Deflections and Stiffness for Orthopaedic Applications.

The implementation of novel coaxial dipole antennas has been shown to be a satisfactory diagnostic platform for the prediction of orthopaedic bone fracture healing outcomes. These techniques require mechanical deflection of implanted metallic hardware (i.e., rods and plates), which, when loaded, produce measurable changes in the resonant frequency of the adjacent antenna. Despite promising initial results, the coiled coaxial antenna design is limited by large antenna sizes and nonlinearity in the resonant frequency data. The purpose of this study was to develop two Vivaldi antennas (a.k.a., "standard" and "miniaturized") to address these challenges. Antenna behaviors were first computationally modeled prior to prototype fabrication. In subsequent benchtop tests, metallic plate segments were displaced from the prototype antennas via precision linear actuator while measuring resultant change in resonant frequency. Close agreement was observed between computational and benchtop results, where antennas were highly sensitive to small displacements of the metallic hardware, with sensitivity decreasing nonlinearly with increasing distance. Greater sensitivity was observed for the miniaturized design for both stainless steel and titanium implants. Additionally, these data demonstrated that by taking resonant frequency data during implant displacement and then again during antenna displacement from the same sample, via linear actuators, that "antenna calibration procedures" could be used to enable a clinically relevant quantification of fracture stiffness from the raw resonant frequency data. These improvements mitigate diagnostic challenges associated with nonlinear resonant frequency response seen in previous antenna designs.

Multiscale Contrasts Between the Right and Left Ventricle Biomechanics in Healthy Adult Sheep and Translational Implications.

Cardiac biomechanics play a significant role in the progression of structural heart diseases (SHDs). SHDs alter baseline myocardial biomechanics leading to single or bi-ventricular dysfunction. But therapies for left ventricle (LV) failure patients do not always work well for right ventricle (RV) failure patients. This is partly because the basic knowledge of baseline contrasts between the RV and LV biomechanics remains elusive with limited discrepant findings. The aim of the study was to investigate the multiscale contrasts between LV and RV biomechanics in large animal species. We hypothesize that the adult healthy LV and RV have distinct passive anisotropic biomechanical properties. Ex vivo biaxial tests were performed in fresh sheep hearts. Histology and immunohistochemistry were performed to measure tissue collagen. The experimental data were then fitted to a Fung type model and a structurally informed model, separately. We found that the LV was stiffer in the longitudinal (outflow tract) than circumferential direction, whereas the RV showed the opposite anisotropic behavior. The anisotropic parameter K from the Fung type model accurately captured contrasting anisotropic behaviors in the LV and RV. When comparing the elasticity in the same direction, the LV was stiffer than the RV longitudinally and the RV was stiffer than the LV circumferentially, suggesting different filling patterns of these ventricles during diastole. Results from the structurally informed model suggest potentially stiffer collagen fibers in the LV than RV, demanding further investigation. Finally, type III collagen content was correlated with the low-strain elastic moduli in both ventricles. In summary, our findings provide fundamental biomechanical differences between the chambers. These results provide valuable insights for guiding cardiac tissue engineering and regenerative studies to implement chamber-specific matrix mechanics, which is particularly critical for identifying biomechanical mechanisms of diseases or mechanical regulation of therapeutic responses. In addition, our results serve as a benchmark for image-based inverse modeling technologies to non-invasively estimate myocardial properties in the RV and LV.

A Large Animal Model for Orthopedic Foot and Ankle Research.

Trauma to the soft tissues of the ankle joint distal syndesmosis often leads to syndesmotic instability, resulting in undesired movement of the talus, abnormal pressure distributions, and ultimately arthritis if deterioration progresses without treatment. Historically, syndesmotic injuries have been repaired by placing a screw across the distal syndesmosis to provide rigid fixation to facilitate ligament repair. While rigid syndesmotic screw fixation immobilizes the ligamentous injury between the tibia and fibula to promote healing, the same screws inhibit normal physiologic movement and dorsiflexion. It has been shown that intact screw removal can be beneficial for long-term patient success; however, the exact timing remains an unanswered question that necessitates further investigation, perhaps using animal models. Because of the sparsity of relevant preclinical models, the purpose of this study was to develop a new, more translatable, large animal model that can be used for the investigation of clinical foot and ankle implants. Eight (8) skeletally mature sheep underwent stabilization of the left and right distal carpal bones following transection of the dorsal and interosseous ligaments while the remaining two animals served as un-instrumented controls. Four of the surgically stabilized animals were sacrificed 6 weeks after surgery while the remaining four animals were sacrificed 10 weeks after surgery. Ligamentous healing was evaluated using radiography, histology, histomorphometry, and histopathology. Overall, animals demonstrated a high tolerance to the surgical procedure with minimal complications. Animals sacrificed at 10 weeks post-surgery had a slight trend toward mildly decreased inflammation, decreased necrotic debris, and a slight increase in the healing of the transected ligaments. The overall degree of soft tissue fibrosis/fibrous expansion, including along the dorsal periosteal surfaces/joint capsule of the carpal bones was very similar between both timepoints and often exhibited signs of healing. The findings of this study indicate that the carpometacarpal joint may serve as a viable location for the investigation of human foot and ankle orthopedic devices. Future work may include the investigation of orthopedic foot and ankle medical devices, biologic treatments, and repair techniques in a large animal model capable of providing translational results for human treatment.

The Interventricular Septum Is Biomechanically Distinct from the Ventricular Free Walls.

The interventricular septum contributes to the pumping function of both ventricles. However, unlike the ventricular wall, its mechanical behavior remains largely unknown. To fill the knowledge gap, this study aims to characterize the biaxial and transmural variation of the mechanical properties of the septum and compare it to the free walls of the left and right ventricles (LV/RV). Fresh hearts were obtained from healthy, adult sheep. The septal wall was sliced along the mid-line into two septal sides and compared to the epicardial layers of the LV- and RV-free walls. Biaxial tensile mechanical tests and constitutive modeling were performed to obtain the passive mechanical properties of the LV- and RV-side of the septum and ventricular walls. We found that both sides of the septum were significantly softer than the respective ventricular walls, and that the septum presented significantly less collagen than the ventricular walls. At low strains, we observed the symmetric distribution of the fiber orientations and a similar anisotropic behavior between the LV-side and RV-side of the septum, with a stiffer material property in the longitudinal direction, rather than the circumferential direction. At high strains, both sides showed isotropic behavior. Both septal sides had similar intrinsic elasticity, as evidenced by experimental data and constitutive modeling. These new findings offer important knowledge of the biomechanics of the septum wall, which may deepen the understanding of heart physiology.

Evaluation of lumbar spinal fusion utilizing recombinant human platelet derived growth factor-B chain homodimer (rhPDGF-BB) combined with a bovine collagen/ß-tricalcium phosphate (ß-TCP) matrix in an ovine model.

BACKGROUND CONTEXT: While the clinical effectiveness of recombinant human Platelet Derived Growth Factor-B chain homodimer combined with collagen and ß-tricalcium phosphate (rhPDGF-BB + collagen/ß-TCP) treatment for indications involving hindfoot and ankle is well-established, it is not approved for use in spinal interbody fusion, and the use of autograft remains the gold standard. PURPOSE: The purpose of this study was to compare the effects of rhPDGF-BB + collagen/ß-TCP treatment on lumbar spine interbody fusion in an ovine model to those of autograft bone and collagen/ß-TCP treatments using biomechanical, radiographic, and histological assessment techniques. STUDY DESIGN: Thirty-two skeletally mature Columbian Rambouillet sheep were used to evaluate the safety and effectiveness of rhPDGF-BB + collagen/ß-TCP matrix in a lumbar spinal fusion model. Interbody polyetheretherketone (PEEK) cages contained either autograft, rhPDGF-BB + collagen/ß-TCP, collagen/ß-TCP matrix, or left empty. METHODS: Animals were sacrificed 8- or 16-weeks post-surgery. Spinal fusion was evaluated via post-sacrifice biomechanical, micro-computed tomography (µCT), and histological analysis. Outcomes were statistically compared using a two-way analysis of variance (ANOVA) with an alpha value of 0.05 and a Tukey post-hoc test. RESULTS: There were no statistically significant differences between groups within treatment timepoints for flexion-extension, lateral bending, or axial rotation range of motion, neutral zone, neutral zone stiffness, or elastic zone stiffness. µCT bone volume fraction was significantly greater between treatment groups independent of timepoint where Autograft and rhPDGF-BB + collagen/ß-TCP treatments demonstrated significantly greater bone volume fraction as compared to collagen/ß-TCP (P = .026 and P = .038, respectively) and Empty cage treatments (P = .002 and P = .003, respectively). µCT mean bone density fraction was most improved in rhPDGF-BB + collagen/ß-TCP specimens at the 8 week and 16-week timepoints as compared to all other treatment groups. There were no statistically significant differences in histomorphometric measurements of bone, soft tissue, or empty space between rhPDGF-BB + collagen/ß-TCP and autograft treatments. CONCLUSIONS: The results of this study indicate that the use of rhPDGF-BB combined with collagen/ß-TCP promotes spinal fusion comparable to that of autograft bone. CLINICAL SIGNIFICANCE: The data indicate that rhPDGF-BB combined with collagen/ß-TCP promotes spinal fusion comparably to autograft bone treatment and may offer a viable alternative in large animal spinal fusion. Future prospective clinical studies are necessary to fully understand the role of rhPDGF-BB combined with collagen/ß-TCP in human spinal fusion healing.

Diagnostic prediction of ovine fracture healing outcomes via a novel multi-location direct electromagnetic coupling antenna.

BACKGROUND: Expedient prediction of adverse bone fracture healing (delayed- or non-union) is necessary to advise secondary treatments for improving healing outcome to minimize patient suffering. Radiographic imaging, the current standard diagnostic, remains largely ineffective at predicting nonunions during the early stages of fracture healing resulting in mean nonunion diagnosis times exceeding six months. Thus, there remains a clinical deficit necessitating improved diagnostic techniques. It was hypothesized that adverse fracture healing expresses impaired biological progression at the fracture site, thus resulting in reduced temporal progression of fracture site stiffness which may be quantified prior to the appearance of radiographic indicators of fracture healing (i.e., calcified tissue). METHODS: A novel multi-location direct electromagnetic coupling antenna was developed to diagnose relative changes in the stiffness of fractures treated by metallic orthopaedic hardware. The efficacy of this diagnostic was evaluated during fracture healing simulated by progressive destabilization of cadaveric ovine metatarsals treated by locking plate fixation (n=8). An ovine in vivo comparative fracture study (n=8) was then utilized to better characterize the performance of the developed diagnostic in a clinically translatable setting. In vivo measurements using the developed diagnostic were compared to weekly radiographic images and postmortem biomechanical, histological, and micro computed tomography analyses. RESULTS: For all cadaveric samples, the novel direct electromagnetic coupling antenna displayed significant differences at the fracture site (P<0.05) when measuring a fully fractured sample versus partially intact and fully intact fracture states. In subsequent in vivo fracture models, this technology detected significant differences (P<0.001) in fractures trending towards delayed healing during the first 30 days post-fracture. CONCLUSIONS: This technology, relative to traditional X-ray imaging, exhibits potential to greatly expedite clinical diagnosis of fracture nonunion, thus warranting additional technological development.

Different Passive Viscoelastic Properties Between the Left and Right Ventricles in Healthy Adult Ovine.

Ventricle dysfunction is the most common cause of heart failure, which leads to high mortality and morbidity. The mechanical behavior of the ventricle is critical to its physiological function. It is known that the ventricle is anisotropic and viscoelastic. However, the understanding of ventricular viscoelasticity is much less than that of its elasticity. Moreover, the left and right ventricles (LV&RV) are different in embryologic origin, anatomy, and function, but whether they distinguish in viscoelastic properties is unclear. We hypothesized that passive viscoelasticity is different between healthy LVs and RVs. Ex vivo cyclic biaxial tensile mechanical tests (1, 0.1, 0.01 Hz) and stress relaxation (strain of 3, 6, 9, 12, 15%) were performed for ventricles from healthy adult sheep. Outflow track direction was defined as the longitudinal direction. Hysteresis stress-strain loops and stress relaxation curves were obtained to quantify the viscoelastic properties. We found that the RV had more pronounced frequency-dependent viscoelastic changes than the LV. Under the physiological frequency (1 Hz), the LV was more anisotropic in the elasticity and stiffer than the RV in both directions, whereas the RV was more anisotropic in the viscosity and more viscous than the LV in the longitudinal direction. The LV was quasi-linear viscoelastic in the longitudinal but not circumferential direction, and the RV was nonlinear viscoelastic in both directions. This study is the first to investigate passive viscoelastic differences in healthy LVs and RVs, and the findings will deepen the understanding of biomechanical mechanisms of ventricular function.

Investigation of a Prevascularized Bone Graft for Large Defects in the Ovine Tibia.

In vivo bioreactors are a promising approach for engineering vascularized autologous bone grafts to repair large bone defects. In this pilot parametric study, we first developed a three-dimensional (3D) printed scaffold uniquely designed to accommodate inclusion of a vascular bundle and facilitate growth factor delivery for accelerated vascular invasion and ectopic bone formation. Second, we established a new sheep deep circumflex iliac artery (DCIA) model as an in vivo bioreactor for engineering a vascularized bone graft and evaluated the effect of implantation duration on ectopic bone formation. Third, after 8 weeks of implantation around the DCIA, we transplanted the prevascularized bone graft to a 5 cm segmental bone defect in the sheep tibia, using the custom 3D printed bone morphogenic protein 2 (BMP-2) loaded scaffold without prior in vivo bioreactor maturation as a control. Analysis by micro-computed tomography and histomorphometry found ectopic bone formation in BMP-2 loaded scaffolds implanted for 8 and 12 weeks in the iliac pouch, with greater bone formation occurring after 12 weeks. Grafts transplanted to the tibial defect supported bone growth, mainly on the periphery of the graft, but greater bone growth and less soft tissue invasion was observed in the avascular BMP-2 loaded scaffold implanted directly into the tibia without prior in vivo maturation. Histopathological evaluation noted considerably greater vascularity in the bone grafts that underwent in vivo maturation with an inserted vascular bundle compared with the avascular BMP-2 loaded graft. Our findings indicate that the use of an initial DCIA in vivo bioreactor maturation step is a promising approach to developing vascularized autologous bone grafts, although scaffolds with greater osteoinductivity should be further studied. Impact statement This translational pilot study aims at combining a tissue engineering scaffold strategy, in vivo prevascularization, and a modified transplantation technique to accelerate large segmental bone defect repair. First, we three-dimensional (3D) printed a 5 cm scaffold with a unique design to facilitate vascular bundle inclusion and osteoinductive growth factor delivery. Second, we established a new sheep deep circumflex iliac artery model as an in vivo bioreactor for prevascularizing the novel 3D printed osteoinductive scaffold. Subsequently, we transplanted the prevascularized bone graft to a clinically relevant 5 cm segmental bone defect in the sheep tibia for bone regeneration.

Osteoinductive 3D printed scaffold healed 5 cm segmental bone defects in the ovine metatarsus.

Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

Mechanical characterization and viscoelastic model of the ovine temporomandibular joint Disc in indentation, uniaxial tension, and biaxial tension.

There have been recent investigations into developing disc replacements and regenerative medicine to treat internal derangements of the temporomandibular joint (TMJ) disc. Previous attempts at disc replacements have faced challenges related in part to a limited understanding of the TMJ's complex mechanical environment. The purpose of this study was to characterize the mechanical behavior of the ovine TMJ disc and to derive viscoelastic constitutive models from the experimental data. Fresh ovine TMJ discs were tested in indentation stress-relaxation tests on the inferior surface, uniaxial tension tests to failure, and dynamic biaxial tensile tests. Results showed an order of magnitude stiffer behavior in tension in the anteroposterior (primary fiber) direction compared to the mediolateral direction. The stiffness in tension was much greater than in compression. Regional comparisons showed greater elastic moduli in indentation in the posterior and anterior bands compared to the central region. A hyper-viscoelastic constitutive model captured the dynamic stress-stretch behavior in both indentation and biaxial tension with good agreement. These data will support ongoing and future computational modeling of local TMJ mechanics, aid in biomaterials identification, and ultimately enhance development of implant designs for TMJ disc replacement.

Direct electromagnetic coupling for non-invasive measurements of stability in simulated fracture healing.

Diagnostic monitoring and prediction of bone fracture healing is critical for the detection of delayed union or non-union and provides the requisite information as to whether therapeutic intervention or timely revision are warranted. A promising approach to monitor fracture healing is to measure the mechanical load-sharing between the healing callus and the implanted hardware used for internal fixation. The objectives of this study were to evaluate a non-invasive measurement system in which an antenna electromagnetically couples with the implanted hardware to sense deflections of the hardware due to an applied load and to investigate the efficacy of the system to detect changes in mechanical load-sharing in an ex vivo fracture healing model. The measurement system was applied to ovine metatarsal bones treated with osteotomies, resulting in four different levels of bone stability which simulated various degrees of fracture healing. Computational finite element simulations supplemented these ex vivo experiments to compare the osteotomy model of fracture healing to a more clinically applicable callus stiffening model of healing. In the ex vivo experiments, the electromagnetic coupling system detected significant differences between the four simulated degrees of healing with good repeatability. Computational simulations indicated that the experimental model of fracture healing provided a good surrogate for studying healing during the early time period as the callus stiffness is increasing as well as when diagnostic monitoring of the healing process is most critical. Based upon the data reported herein, the direct electromagnetic coupling method holds strong potential for clinical assessments and predictions of fracture healing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

An anisotropic hyperelastic constitutive model of brain white matter in biaxial tension and structural-mechanical relationships.

Computational models of the brain require accurate and robust constitutive models to characterize the mechanical behavior of brain tissue. The anisotropy of white matter has been previously demonstrated; however, there is a lack of data describing the effects of multi-axial loading, even though brain tissue experiences multi-axial stress states. Therefore, a biaxial tensile experiment was designed to more fully characterize the anisotropic behavior of white matter in a quasi-static loading state, and the mechanical data were modeled with an anisotropic hyperelastic continuum model. A probabilistic analysis was used to quantify the uncertainty in model predictions because the mechanical data of brain tissue can show a high degree of variability, and computational studies can benefit from reporting the probability distribution of model responses. The axonal structure in white matter can be heterogeneous and regionally dependent, which can affect computational model predictions. Therefore, corona radiata and corpus callosum regions were tested, and histology and transmission electron microscopy were performed on tested specimens to relate the distribution of axon orientations and the axon volume fraction to the mechanical behavior. These measured properties were implemented into a structural constitutive model. Results demonstrated a significant, but relatively low anisotropic behavior, yet there were no conclusive mechanical differences between the two regions tested. The inclusion of both biaxial and uniaxial tests in model fits improved the accuracy of model predictions. The mechanical anisotropy of individual specimens positively correlated with the measured axon volume fraction, and, accordingly, the structural model exhibited slightly decreased uncertainty in model predictions compared to the model without structural properties.

Optical Coherence Tomographic Elastography Reveals Mesoscale Shear Strain Inhomogeneities in the Annulus Fibrosus.

STUDY DESIGN: Basic science study using in vitro tissue testing and imaging to characterize local strains in annulus fibrosus (AF) tissue. OBJECTIVE: To characterize mesoscale strain inhomogeneities between lamellar and inter-/translamellar (ITL) matrix compartments during tissue shear loading. SUMMARY OF BACKGROUND DATA: The intervertebral disc is characterized by significant heterogeneities in tissue structure and plays a critical role in load distribution and force transmission in the spine. In particular, the AF possesses a lamellar architecture interdigitated by a complex network of extracellular matrix components that form a distinct ITL compartment. Currently, there is not a firm understanding of how the lamellar and ITL matrix coordinately support tissue loading. METHODS: AF tissue samples were prepared from frozen porcine lumbar spines and mounted onto custom fixtures of a materials testing system that incorporates optical coherence tomography (OCT) imaging to perform tissue elastography. Tissues were subjected to 20 and 40% nominal shear strain, and OCT images were captured and segmented to identify regions of interest corresponding to lamellar and ITL compartments. Images were analyzed using an optical flow algorithm to quantify local shear strains within each compartment. RESULTS: Using histology and OCT, we first verified our ability to visualize and discriminate the ITL matrix from the lamellar matrix in porcine AF tissues. Local AF strains in the ITL compartment (22.0 ±â€Š13.8, 31.1 ±â€Š16.9 at 20% and 40% applied shear, respectively) were significantly higher than corresponding strains in the surrounding lamellar compartment (12.1 ±â€Š5.6, 15.3 ±â€Š5.2) for all tissue samples (P < 0.05). CONCLUSION: Results from this study demonstrate that the lamellar and ITL compartments of the AF distribute strain unevenly during tissue loading. Specifically, shear strain is significantly higher in the ITL matrix, suggesting that these regions may be more susceptible to tissue damage and more mechanobiologically active. LEVEL OF EVIDENCE: N/A.

A computational model to describe the regional interlamellar shear of the annulus fibrosus.

Interlamellar shear may play an important role in the homeostasis and degeneration of the intervertebral disk. Accurately modeling the shear behavior of the interlamellar compartment would enhance the study of its mechanobiology. In this study, physical experiments were utilized to describe interlamellar shear and define a constitutive model, which was implemented into a finite element analysis. Ovine annulus fibrosus (AF) specimens from three locations within the intervertebral disk (lateral, outer anterior, and inner anterior) were subjected to in vitro mechanical shear testing. The local shear stress-stretch relationship was described for the lamellae and across the interlamellar layer of the AF. A hyperelastic constitutive model was defined for interlamellar and lamellar materials at each location tested. The constitutive models were incorporated into a finite element model of a block of AF, which modeled the interlamellar and lamellar layers using a continuum description. The global shear behavior of the AF was compared between the finite element model and physical experiments. The shear moduli at the initial and final regions of the stress-strain curve were greater within the lamellae than across the interlamellar layer. The difference between interlamellar and lamellar shear was greater at the outer anterior AF than at the inner anterior region. The finite element model was shown to accurately predict the global shear behavior or the AF. Future studies incorporating finite element analysis of the interlamellar compartment may be useful for predicting its physiological mechanical behavior to inform the study of its mechanobiology.