Significance of the collagen criss-cross angle distributions in lumbar annuli fibrosi as revealed by finite element simulations

In the human lumbar spine, annulus fibr osus (AF) fibres la rgely contribute to intervertebral disc (IVD) stability, and deta iled annulus models are required to obtain reliable predictions of lumbar spine biom echanics by finite element (FE) modelling. However, different definitions of collagen orientation coexist in the literature for healthy human lumbar AFs and are indiscrimi nately used in mode lling. Therefore, four AF fibre-induced anisotropy models were bu ilt from reported anatomical descriptions and inserted in a L3-L5 lumbar bi-segment FE model. AF models were respectively characterized by radial, tange ntial, radial and tangentia l, and no fibre orientation gradients. IVD local biomechanics was studied under axial rotation and axial compression. A new parameter, i.e. the Fi bre Contribution Qual ity parameter, was computed in the anterior, lateral, postero-l ateral and posterior AFs of each model, in function of fibre stresses, load distributions, and matrix shear strains. Locally, each AF model behaved differently, affecting the IVD biomechanics. The Fibre Contribution Quality (FCQ) parameter established a direct link between local AF fibre organization and loading, while other biomechanical data did not. It was conc luded that local AF fibre orientations should be modelled in rela tion to other segment characteristics. The proposed FCQ parameter could be used to examine such relations, being, therefore particularly relevant to patient-specifi c models or artificial disc designs.Postprint (published version

Regional annulus fibre orientations used as a tool for the calibration of lumbar intervertebral disc finite element models

The highly organized collagen network of human lumbar a nnulus fibrosus (AF) is fundamental to preserve the mechanical inte grity of the interverte bral discs. In the healthy AF, fibres are embedded in a hydrated matrix and arranged in a criss-cross fashion, giving an anisotropic structure capab le to undergo large st rains. Quantitative anatomical examinations revealed particular fibre orientation patterns, possibly coming from regional adaptations of the AF mechan ics. Based on such hypothesis, this study aimed to show that the regional differen ces in AF mechanical behaviour can be reproduced by considering only fibre orientatio n changes. Using the finite element (FE) method, AF matrix was modelled as a poro-hy perelastic material, where the porous solid was treated as a comp ressible continuum following a Neo-Hookean constitutive law. Strain-dependent permeability was assumed and all material parameters were taken from the literature. Fibre reinforcement wa s accounted for by adding an extra-term to the porous matrix strain energy density func tion, only active along th e fibre directions. Through such term, fibre orientations were then adjusted, to reproduce AF tensile behaviours measured for four different regi ons: posterior outer (PO), anterior outer (AO), posterior inner (PI) and anterior inne r (AI). Curve calibrations resulted in the following optimal angles, calculated with respect to the circumferential axis: 28º for PO, 23º for AO, 43º for PI and 31º for AI. In average, we obtained fibres 30% more transversal in the inner than in the outer AF against 38% as measured by Cassidy et al. (1989). Fibres more axial in the posterior than in the anterior AF were also measured by Holzapfel et al. (2005), with angle values comparable to our computed average values. Since all the hyperelastic and fluid-phase material parameters remained unchanged throughout the AF, calibration based only on fibre patterns variations may be an effective tool to calibrate the regional AF mechanics in a realistic way.Postprint (published version

A micro-macro evaluation of the vertebral bony endplate permeability based on computational fluid dynamics

The intrinsic permeability is an important parameter that describes the resistance of a porous structure to fluid flo w. It has a key role in poroelastic finite element models of spinal segments, especially at the vertebral endplate, i.e. the interface between intervertebral disc and vertebra. In the understanding of the properties of the complex endplate system, an expli cit evaluation for permeability of subchondral bone is missing. Thus, a new method wa s proposed to evaluate the intrinsic permeability of the bony endplate. CT - based reconstruction s of the bony endplate from a lumbar vertebra were analyzed using computational fluid dynamics , and the i ntrinsic permeability and porosity of the structure were calculated. Results showed that the permeability did not depend on the fluid flow direction, and was statistically similar for both the superior and inferior endplates . Permeability values varied within the range of trabecular bone, while porosity values w ere lower than trabecular bone characteristic values. Finally, i ntrins ic permeability correlated well with porosity through the Kozeny - Karman model, which offer s perspectives for parametric studies involving degenerative or age - related changes at the disc - bone interface.Postprint (published version

Clavos intramedulares vs. placas de osteosíntesis para fracturas de fémur. Análisis por elementos finitos

La estabilización interna de fracturas de la diáfisis femoral se realiza mediante la implantación de clavos intramedulares o placas de osteosíntesis. El objetivo de este estudio es realizar una comparación biomecánica por elementos finitos de ambos implantes y así desarrollar una herramienta preclínica para guiar a los cirujanos en la elección del método de estabilización más adecuado para cada fractura. Se malló un fémur entero en el cual se practicó una fractura de 1mm ó 3mm en la diáfisis. Los modelos de placa y clavo se mallaron a partir de la geometría de los implantes, para el clavo se realizaron dos modelos con diámetros distintos (11 y 13 mm). El estudio incluye simulaciones en dos etapas de regeneración de la fractura (con modulo de elasticidad en la fractura de 1 MPa ó 10 MPa), con implantes de acero inoxidable y titanio. Las cargas aplicadas simulan el apoyo monopodal e incluyen la actuación de la cadera, y los músculos abductores, psoas ilíaco e iliotibial. Los resultados muestran que la tensión en los implantes aumenta con el tamaño de la fractura y disminuye con su módulo. Los clavos tienden a inducir más deformación en la fractura que las placas. El diámetro de los clavos influye en la tensión inducida en el hueso y en la deformación en la fractura, los resultados de los clavos más anchos tienden a los resultados de las placas

Clavos intramedulares vs. placas de osteosíntesis para fracturas de fémur: Análisis por elementos finitos.

La estabilización interna de fracturas de la diáfisis femoral se realiza mediante la implantación de clavos intramedulares o placas de osteosíntesis. El objetivo de este estudio es realizar una comparación biomecánica por elementos finitos de ambos implantes y así desarrollar una herramienta preclínica para guiar a los cirujanos en la elección del método de estabilización más adecuado para cada fractura. Se malló un fémur entero en el cual se practicó una fractura de 1mm ó 3mm en la diáfisis. Los modelos de placa y clavo se mallaron a partir de la geometría de los implantes, para el clavo se realizaron dos modelos con diámetros distintos (11 y 13 mm). El estudio incluye simulaciones en dos etapas de regeneración de la fractura (con modulo de elasticidad en la fractura de 1 MPa ó 10 MPa), con implantes de acero inoxidable y titanio. Las cargas aplicadas simulan el apoyo monopodal e incluyen la actuación de la cadera, y los músculos abductores, psoas ilíaco e iliotibial. Los resultados muestran que la tensión en los implantes aumenta con el tamaño de la fractura y disminuye con su módulo. Los clavos tienden a inducir más deformación en la fractura que las placas. El diámetro de los clavos influye en la tensión inducida en el hueso y en la deformación en la fractura, los resultados de los clavos más anchos tienden a los resultados de las placas

Focused ultrasound excites neurons via mechanosensitive calcium accumulation and ion channel amplification

Ultrasonic neuromodulation has the unique potential to provide non-invasive control of neural activity in deep brain regions with high spatial precision and without chemical or genetic modification. However, the biomolecular and cellular mechanisms by which focused ultrasound excites mammalian neurons have remained unclear, posing significant challenges for the use of this technology in research and potential clinical applications. Here, we show that focused ultrasound excites neurons through a primarily mechanical mechanism mediated by specific calcium-selective mechanosensitive ion channels. The activation of these channels results in a gradual build-up of calcium, which is amplified by calcium- and voltage-gated channels, generating a burst firing response. Cavitation, temperature changes, large-scale deformation, and synaptic transmission are not required for this excitation to occur. Pharmacological and genetic inhibition of specific ion channels leads to reduced responses to ultrasound, while over-expressing these channels results in stronger ultrasonic stimulation. These findings provide a critical missing explanation for the effect of ultrasound on neurons and facilitate the further development of ultrasonic neuromodulation and sonogenetics as unique tools for neuroscience research

Nanotechnology in regenerative medicine: the materials side

Regenerative medicine is an emerging multidisciplinary field that aims to restore, maintain or enhance tissues and hence organ functions. Regeneration of tissues can be achieved by the combination of living cells, which will provide biological functionality, and materials, which act as scaffolds to support cell proliferation. Mammalian cells behave in vivo in response to the biological signals they receive from the surrounding environment, which is structured by nanometre-scaled components. Therefore, materials used in repairing the human body have to reproduce the correct signals that guide the cellstowards a desirable behaviour. Nanotechnology is not only an excellent tool to produce material structures that mimic the biological ones but also holds the promise of providing efficient delivery systems. The application of nanotechnology to regenerative medicine is a wide issue and this short review will only focus on aspects of nanotechnology relevant to biomaterials science. Specifically, the fabrication of materials, such as nanoparticles and scaffolds for tissue engineering, and the nanopatterning of surfaces aimed at eliciting specific biological responses from the host tissue will be addressed.Postprint (published version

Molecular mechanism for depolarization-induced modulation of Kv channel closure

Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K(+) permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K(+) conduction through constriction of the K(+) selectivity filter. Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the subsequent membrane repolarization. Measurements of deactivating gating currents (reporting VSD movement) and ionic currents (BC gate status) showed that the kinetics of both slowed down in two distinct phases with increasing duration of the depolarizing prepulse. The biphasic slowing in VSD deactivation and BC gate closure was strongly correlated in time and magnitude. Simultaneous recordings of ionic currents and fluorescence from a probe tracking VSD movement in Shaker directly demonstrated that both processes were synchronized. Whereas the first slowing originates from a stabilization imposed by BC gate opening, the subsequent slowing reflects the rearrangement of the VSD toward its relaxed state (relaxation). The VSD relaxation was observed in the Ciona intestinalis voltage-sensitive phosphatase and in its isolated VSD. Collectively, our results show that the VSD relaxation is not kinetically related to C-type inactivation and is an intrinsic property of the VSD. We propose VSD relaxation as a general mechanism for depolarization-induced slowing of BC gate closure that may enable Kv1.2 channels to modulate the firing frequency of neurons based on the depolarization history

Molecular mechanism for depolarization-induced modulation of Kv channel closure

Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K+ permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K+ conduction through constriction of the K+ selectivity filter. Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the subsequent membrane repolarization. Measurements of deactivating gating currents (reporting VSD movement) and ionic currents (BC gate status) showed that the kinetics of both slowed down in two distinct phases with increasing duration of the depolarizing prepulse. The biphasic slowing in VSD deactivation and BC gate closure was strongly correlated in time and magnitude. Simultaneous recordings of ionic currents and fluorescence from a probe tracking VSD movement in Shaker directly demonstrated that both processes were synchronized. Whereas the first slowing originates from a stabilization imposed by BC gate opening, the subsequent slowing reflects the rearrangement of the VSD toward its relaxed state (relaxation). The VSD relaxation was observed in the Ciona intestinalis voltage-sensitive phosphatase and in its isolated VSD. Collectively, our results show that the VSD relaxation is not kinetically related to C-type inactivation and is an intrinsic property of the VSD. We propose VSD relaxation as a general mechanism for depolarization-induced slowing of BC gate closure that may enable Kv1.2 channels to modulate the firing frequency of neurons based on the depolarization history