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Tissue scaffolds provide structural support while facilitating tissue growth, but are challenging to design due to diverse property trade-offs. Here, a computational approach was developed for modeling scaffolds with lattice structures of eight different topologies and assessing properties relevant to bone tissue engineering applications. Evaluated properties include porosity, pore size, surface-volume ratio, elastic modulus, shear modulus, and permeability. Lattice topologies were generated by patterning beam-based unit cells, with design parameters for beam diameter and unit cell length. Finite element simulations were conducted for each topology and quantified how elastic modulus and shear modulus scale with porosity, and how permeability scales with porosity cubed over surface-volume ratio squared. Lattices were compared with controlled properties related to porosity and pore size. Relative comparisons suggest that lattice topology leads to specializations in achievable properties. For instance, Cube topologies tend to have high elastic and low shear moduli while Octet topologies have high shear moduli and surface-volume ratios but low permeability. The developed method was utilized to analyze property trade-offs as beam diameter was altered for a given topology, and used to prototype a 3D printed lattice embedded in an interbody cage for spinal fusion treatments. Findings provide a basis for modeling and understanding relative differences among beam-based lattices designed to facilitate bone tissue growth.

Musculoskeletal models represent a powerful tool to gain knowledge on the internal forces acting at the joint level in a non-invasive way. However, these models can present some errors associated with the level of detail in their geometrical representation. For this reason, a thorough validation is necessary to prove the reliability of their predictions. This study documents the development of a generic musculoskeletal model and proposes a working logic and simulation techniques for identifying specific model features in need of refinement; as well as providing a quantitative validation for the prediction of hip contact forces (HCF). The model, implemented in the AnyBody Modeling System and based on the cadaveric dataset TLEM 2.0, was scaled to match the anthropometry of a patient fitted with an instrumented hip implant and to reproduce gait kinematics based on motion capture data. The relative contribution of individual muscle elements to the HCF and joint moments was analyzed to identify critical geometries, which were then compared to muscle magnetic resonance imaging (MRI) scans and, in case of inconsistencies, were modified to better match the volumetric scans. The predicted HCF showed good agreement with the overall trend and timing of the measured HCF from the instrumented prosthesis. The average root mean square error (RMSE), calculated for the total HCF was found to be 0.298*BW. Refining the geometries of the muscles thus identified reduced RMSE on HCF magnitudes by 17% (from 0.359*BW to 0.298*BW) over the whole gait cycle. The detailed study of individual muscle contributions to the HCF succeeded in identifying muscles with incorrect anatomy, which would have been difficult to intuitively identify otherwise. Despite a certain residual over-prediction of the final hip contact forces in the stance phase, a satisfactory level of geometrical accuracy of muscle paths has been achieved with the refinement of this model.

Silicon nitride possesses a variety of excellent properties that can be specifically designed and manufactured for different medical applications. On the one hand, silicon nitride is known to have good mechanical properties, such as high strength and fracture toughness. On the other hand, the uniqueness of the osteogenic/antibacterial dualism of silicon nitride makes it a favorable bioceramic for implants. The surface of silicon nitride can simultaneously inhibit the proliferation of bacteria while supporting the physiological activities of eukaryotic cells and promoting the healing of bone tissue. There are hardly any biomaterials that possess all these properties concurrently. Although silicon nitride has been intensively studied as a biomedical material for years, there is a paucity of comprehensive data on its properties and medical applications. To provide a comprehensive understanding of this potential cornerstone material of the medical field, this review presents scientific and technical data on silicon nitride, including its mechanical properties, osteogenic behavior, and antibacterial capabilities. In addition, this paper highlights the current and potential medical use of silicon nitride and explains the bottlenecks that need to be addressed, as well as possible solutions.

Huntington’s disease (HD) is a neurodegenerative disorder caused by a genetic abnormality in the huntingtin gene that leads to a polyglutamine repeat expansion of the huntingtin protein. The cleaved polyglutamine expansion of mutant huntingtin (mHTT) protein can form aggregates strongly correlated with HD progression. We have previously shown that the inhibition of mGluR5 using CTEP, a selective negative allosteric mGluR5 modulator, can delay disease progression and reduce in mHTT aggregates in the zQ 175 mouse model of HD. This was paralleled by enhanced catalytic activity of Unc-51-like kinase 1 (ULK1), a kinase modulated by mammalian target of rapamycin (mTOR) and key regulator of autophagy initiation. In the present study, we show that CTEP can correct aberrant phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling detected in zQ 175 mice that may underlie the enhanced ULK1 activity and activation of autophagy. We also show that CTEP can facilitate cAMP response element-binding protein (CREB)-mediated expression of brain-derived neurotrophic factor (BDNF) to foster neuronal survival and reduce apoptosis. Taken together, our findings provide the molecular evidence for how targeting mGluR5 using a well-tolerated selective NAM can mitigate two critical mechanisms of neurodegeneration, autophagy and apoptosis.

Musculoskeletal modeling offers an invaluable insight into the spine biomechanics. A better understanding of thoracic spine kinetics is essential for understanding disease processes and developing new prevention and treatment methods. Current models of the thoracic region are not designed for segmental load estimation, or do not include the complex construct of the ribcage, despite its potentially important role in load transmission. In this paper, we describe a numerical musculoskeletal model of the thoracolumbar spine with articulated ribcage, modeled as a system of individual vertebral segments, elastic elements and thoracic muscles, based on a previously established lumbar spine model and data from the literature. The inverse dynamics simulations of the model allow the prediction of spinal loading as well as costal joints kinetics and kinematics. The intradiscal pressure predicted by the model correlated well (R2=0.89) with reported intradiscal pressure measurements, providing a first validation of the model. The inclusion of the ribcage did not affect segmental force predictions when the thoracic spine did not perform motion. During thoracic motion tasks, the ribcage had an important influence on the predicted compressive forces and muscle activation patterns. The compressive forces were reduced by up to 32%, or distributed more evenly between thoracic vertebrae, when compared to the predictions of the model without ribcage, for mild thoracic flexion and hyperextension tasks, respectively. The presented musculoskeletal model provides a tool for investigating thoracic spine loading and load sharing between vertebral column and ribcage during dynamic activities. Further validation for specific applications is still necessary.

Musculoskeletal simulations with muscle optimization aim to minimize muscle effort, hence are considered unable to predict the activation of antagonistic muscles. However, activation of antagonistic muscles might be necessary to satisfy the dynamic equilibrium. This study aims to elucidate under which conditions coactivation can be predicted, to evaluate factors modulating it, and to compare the antagonistic activations predicted by the lumbar spine model with literature data. Simple 2D and 3D models, comprising of 2 or 3 rigid bodies, with simple or multi-joint muscles, were created to study conditions under which muscle coactivity is predicted. An existing musculoskeletal model of the lumbar spine developed in AnyBody was used to investigate the effects of modeling intra-abdominal pressure (IAP), linear/cubic and load/activity-based muscle recruitment criterion on predicted coactivation during forward flexion and lateral bending. The predicted antagonist activations were compared to reported EMG data. Muscle coactivity was predicted with simplified models when multi-joint muscles were present or the model was three-dimensional. During forward flexion and lateral bending, the coactivation ratio predicted by the model showed good agreement with experimental values. Predicted coactivation was negligibly influenced by IAP but substantially reduced with a force-based recruitment criterion. The conditions needed in multi-body models to predict coactivity are: three-dimensionality or multi-joint muscles, unless perfect antagonists. The antagonist activations are required to balance 3D moments but do not reflect other physiological phenomena, which might explain the discrepancies between model predictions and experimental data. Nevertheless, the findings confirm the ability of the multi-body trunk models to predict muscle coactivity and suggest their overall validity.

Videofluoroscopy has been shown to provide essential information in the evaluation of the functionality of total knee arthroplasties. However, due to the limitation in the field of view, most systems can only assess knee kinematics during highly restricted movements. To avoid the limitations of a static image intensifier, a moving fluoroscope has been presented as a standalone system that allows tracking of the knee during multiple complete cycles of level- and downhill-walking, as well as stair descent, in combination with the synchronous assessment of ground reaction forces and whole body skin marker measurements. Here, we assess the ability of the system to keep the knee in the field of view of the image intensifier. By measuring ten total knee arthroplasty subjects, we demonstrate that it is possible to maintain the knee to within 1.8 ± 1.4 cm vertically and 4.0 ± 2.6 cm horizontally of the centre of the intensifier throughout full cycles of activities of daily living. Since control of the system is based on real-time feedback of a wire sensor, the system is not dependent on repeatable gait patterns, but is rather able to capture pathological motion patterns with low inter-trial repeatability.

•Disciplines such as biomaterials, biofabrication, and tissue engineering are converging to create more advanced tissue-like constructs that accurately reproduce detailed physical and biological properties.•Researchers now have access to a range of tools that enable them to replicate microenvironmental features such as heterogeneity, anisotropy, hierarchical structures, compositional gradients and interfaces, and spatiotemporal cues.•Advanced models are strengthening our understanding of the mechanisms that govern tissue function and disease.•While not fully resembling the complexity of human tissue, engineered models enable researchers to investigate and adapt subsets of parameters, addressing targeted research questions. Advances in tissue engineering for both system modeling and organ regeneration depend on embracing and recapitulating the target tissue’s functional and structural complexity. Microenvironmental features such as anisotropy, heterogeneity, and other biochemical and mechanical spatiotemporal cues are essential in regulating tissue development and function. Novel biofabrication strategies and innovative biomaterial design have emerged as promising tools to better reproduce such features. These facilitate a transition towards high-fidelity biomimetic structures, offering opportunities for a deeper understanding of tissue function and the development of superior therapies. In this review, we explore some of the key structural and compositional aspects of tissues, lay out how to achieve similar outcomes with current fabrication strategies, and identify the main challenges and promising avenues for future research. Advances in tissue engineering for both system modeling and organ regeneration depend on embracing and recapitulating the target tissue’s functional and structural complexity. Microenvironmental features such as anisotropy, heterogeneity, and other biochemical and mechanical spatiotemporal cues are essential in regulating tissue development and function. Novel biofabrication strategies and innovative biomaterial design have emerged as promising tools to better reproduce such features. These facilitate a transition towards high-fidelity biomimetic structures, offering opportunities for a deeper understanding of tissue function and the development of superior therapies. In this review, we explore some of the key structural and compositional aspects of tissues, lay out how to achieve similar outcomes with current fabrication strategies, and identify the main challenges and promising avenues for future research.

Arthroplasty in the cervical spine is performed using Total Disc Replacement (TDR) implants. This study investigates the safety and tribology of a design-optimized ceramic TDR bearing. Samples of an optimized bearing geometry were manufactured from the bioceramic BIOLOX®delta (CeramTec GmbH, Germany) and tested in a six degree of freedom universal joint simulator in diluted calf serum at body temperature. The investigated load and motion profiles simulated movements of daily living; three pure rotations under static load and three rotations coupled under sinusoidal load as well as adverse events (three subluxation test conditions). Dynamic coefficients of friction during flexion/extension and lateral bending were µ = 0.16 ± 0.011 and µ = 0.16 ± 0.070, respectively. Friction factors during flexion/extension and lateral bending were f = 0.14 ± 0.0092 and f = 0.13 ± 0.063, whereas the friction factor in axial rotation was f = 0.033 ± 0.0028 and for three coupled rotations under sinusoidal load, it was f = 0.13 ± 0.028. The design demonstrated a sufficient resistance against subluxation, with subluxation forces more than 3.5-fold the 20N that are typically required as acceptance criteria in FDA safety and effectiveness data. Friction values were found to be comparable to or higher than those typically reported for ceramic-on-ceramic hip replacements. Furthermore, the results indicated that the optimized bearing design is sufficiently resistant to subluxation. Significance: Test protocols to investigate safety and tribology of cervical TDRs are proposed and their results are reported for a design-optimized ceramic TDR bearing.

The majority of hip fractures have been reported to occur as a result of a fall with impact to the greater trochanter of the femur. Recently, we developed a novel cadaveric pendulum-based hip impact model and tested two cadaveric femur-pelvis constructs, embedded in a soft tissue surrogate. The outcome was a femoral neck fracture in a male specimen while a female specimen had no fracture. The aim of the present study was, first, to develop a methodology for constructing and assessing the accuracy of explicit Finite Element Models (FEMs) for simulation of sideways falls to the hip based on the experimental model. Second, to use the FEMs for quantifying the internal reaction forces and energy absorption in the hip during impact. Third, to assess the potential of the FEMs in terms of separating a femoral fracture endpoint from a non-fracture endpoint. Using a non-linear, strain rate dependent, and heterogeneous material mapping strategy for bone tissue in these models, we found the FEM-derived results to closely match the experimental test results in terms of impact forces and displacements of pelvic video markers up to the time of peak impact force with errors below 10%. We found the internal reaction forces in the femoral neck on the impact side to be approximately 35% lower than the impact force measured between soft tissue and ground for both specimens. In addition, we found the soft tissue to be the component that absorbed the largest part of the energy of the tissue types in the hip region. Finally, we found surface strain patterns derived from FEM results to match the fracture location and extent based on post testing x-rays of the specimens. This is the first study with quantitative data on the energy absorption in the pelvic region during a sideways fall.