Journal of the Mechanical Behavior of Biomedical Materials

The human masseter muscle is one of the primary muscles responsible for mastication and mandibular movement; however, its intrinsic mechanical properties remain insufficiently characterized. In this experimental study, the nonlinear, viscoelastic, and history-dependent behaviour of the human masseter muscle was investigated using ex vivo uniaxial cyclic tensile tests. The masseter muscle samples prepared from fresh and formalin-preserved cadavers were tested under two loading protocols: a continuous stretch protocol with increasing stretch levels and a constant stretch protocol with repeated loading to a fixed maximum stretch. Tests were conducted at two strain rates, and their influences on the mechanical behaviour of the tissue were examined. The effect of formalin preservation was also investigated. The results showed that the stiffness of the tissue increases for formalin-preserved samples. Under cyclic loading, the features including energy dissipation, stress-softening, residual deformation, and cyclic conditioning progressively changed during the initial loading cycles and reached stabilization during the final cycle. These findings provide experimental evidence that the human masseter muscle exhibits nonlinear, viscoelastic, and history-dependent mechanical behaviour under cyclic tensile loading. The experimental data obtained in this study may be used for biomechanical modelling of the human masticatory system and the development of constitutive models for cranio-maxillofacial surgical simulation, prosthetic design, and facial soft-tissue biomechanics. Statement of significanceThe masseter muscle is one of the primary muscles of mastication. To address the current gap in craniofacial biomechanics that has largely focused on the mechanical characterization of the masseter muscle based on imaging techniques or monotonic loading, this study quantifies the nonlinear and viscoelastic mechanical response of masseter tissue under cyclic continuous and constant stretch loading, including strain-rate and preservation effects. The results show that the mechanical behaviour of the masseter muscle, including stiffness, hysteresis, stress-softening, and residual strain behaviour, is strongly influenced by strain-rate and formalin preservation. The experimental results provide mechanical data for constitutive modelling of the masticatory system with applications in cranio-maxillofacial surgical simulation, prosthetic design, and facial soft tissue modelling.

I.Bone fragility is a major ang growing public health concern for many with degenerative bone diseases. A better understanding of fracture propagation in bone can better inform treatment options for these individuals. Human bone is an anisotropic material, with directional microstructure that fractures can propagate around. In a healthy individual, the bone remodeling process repairs damaged tissue. Calcium sulfate dihydrate is a well established surrogate material for bone. This study will mechanically investigate damage repaired plaster samples using three point bending to characterize crack propagation around repaired damage.

Keratin proteins are fundamental structural components of hair fibers, contributing to their mechanical resilience, elasticity, and fracture resistance. However, systematic molecular-scale characterization of keratin unfolding mechanics across protein types remains limited, restricting the connection between protein-level deformation mechanisms and hierarchical hair fiber mechanics. Here, we establish a comparative molecular-dynamics-based framework for characterizing the unfolding behavior and nanomechanical response of a curated dataset of 51 keratin proteins. We conduct implicit atomistic molecular dynamics (MD) simulations, including equilibration and steered molecular dynamics (SMD) under four accelerated pulling velocities, to quantify unfolding forces, energy absorption, and structure-property relationships. These accelerated pulling conditions are interpreted as computational probes of relative molecular-scale trends, rather than direct reproductions of experimental hair-fiber strain-rate regimes. Across these accelerated SMD conditions, the simulations show rate-sensitive increases in unfolding force and energy absorption, consistent with constrained molecular relaxation during faster molecular pulling. Stronger correlations between nanomechanical properties and molecular descriptors emerge at higher pulling rates, and the nanomechanical responses of different keratin types (Type I and II) are also compared. The findings provide molecular-level insights into protein unfolding mechanisms that may contribute to the mechanical behavior of hierarchical keratin structures. This study establishes a quantitative framework for comparative keratin unfolding mechanics, providing molecular-level descriptors for future multiscale modeling of hair fiber behavior. These results support applications in biomaterial design, hair fiber durability analysis, and bioinspired material engineering. Future work will integrate these nanomechanical descriptors with fiber-level mechanics and machine learning-based keratin design.

Snake venom composition and its contribution to toxic effects has been heavily researched, but there is a comparative lack of information on venoms fluidic properties and their relationship with fang morphology during the envenomation process. Understanding how venom flows through a fang can shed light on bite site dynamics and potentially explain bite symptoms. In this article we first conduct a broad comparative test of the rheological properties of venom from thirteen snake species, including multiple viperid and elapid snake species, revealing a shear-thinning non-Newtonian flow behavior in all studied species. However, we have not observed strong phylogenetic signal in venom fluidic properties, suggesting that flow properties may vary independently of evolutionary relationships between snake species. Second, we demonstrate that snake venoms fluidic properties can be modeled by other inexpensive, safe, and abundant shear-thinning surrogate fluids. We found that aqueous solutions of bovine serum albumin protein and xanthan gum are useful venom mimics, matching the rheological behavior of venoms from the studied snake species across a range of relevant shear rates. We further evaluated the performance of these snake venom mimics in a simulated venom delivery system, showing good and robust mimetic control of the flow properties as a function of applied pressure. By elucidating the fluidic properties of snake venom and providing a non-toxic, scalable surrogate fluid model to be used in further studies, we provide the biomedical, toxicology, evolutionary biology communities with a tool to study envenomation physics in an inexpensive and safe fashion. We suggest it is possible to design species-specific venom mimics that facilitate research on the biomechanics and fluid dynamics of venom delivery via snake bites, and inform the design of bioinspired puncture and injection devices.

Dysphagia, difficulty swallowing due to irritation or damage to the esophagus, is one of the most common complications following anterior cervical discectomy and fusion (ACDF), the most frequently performed cervical spine procedure in the United States. Surgical retraction hardware imposes sustained compression on the esophagus during surgery, generating nonuniform stress and strain fields that may contribute to temporary postoperative soft tissue damage. Current intraoperative assessment relies on visual inspection and manual inspection by the surgical team and does not provide quantitative measures of esophageal deformation, strain, or retraction displacement. Here, we present a comprehensive mechanics analysis of esophageal compression during ACDF that integrates experiments on esophageal phantoms, nonlinear finite element modeling, and theoretical thick-wall scaling relationships. Modeling results quantify peak contact pressures and corresponding stress distributions, identifying conditions under which circumferential strain in the compressed esophageal wall increases sharply as localized pressures approach the upper physiological range ([~]6-17 kPa). Parametric investigation of retractor blade width, placement depth, and polymeric biocompatible coating properties demonstrates that targeted, yet mechanically simple, design modifications can help to attenuate strain concentrations. In particular, the introduction of compliant polymeric coatings redistributes contact loads and reduces peak wall stress by up to 20% relative to unbuffered blades (17 kPa to 13.5 kPa). Increasing blade width from 20 mm to 50 mm further decreases peak interface stress from 2.48 kPa to 0.45 kPa, corresponding to an 82% reduction. Reducing these stresses may help limit mechanically induced complications such as postoperative dysphagia. Experiments performed on esophageal phantoms with embedded pressure sensors replicate surgical ACDF retraction protocols under displacement-controlled conditions. This setup establishes physiologically relevant loading and enables quantitative validation of computational predictions by correlating measured voltage output with contact pressure and esophageal deformation. Measured relationships between applied retraction displacement, contact pressure, and tissue deformation govern stress amplification during ACDF retraction. Together, these results establish a predictive mechanics framework that links retractor blade design variables to esophageal stress fields, providing quantitative criteria to mitigate soft tissue damage during ACDF. HIGHLIGHTSO_LI2D and 3D finite element models quantify esophageal wall stress during anterior cervical discectomy and fusion (ACDF) retraction. C_LIO_LIRetractor blade geometry influences stress distribution, with wider blades reducing localized tissue loading by up to 82% likely associated with post-surgical dysphagia. C_LIO_LICompliant polymeric buffer layers attenuate pressure and smoothen stress gradients to reduce peak tissue loading by up to 20% during retraction. C_LI

Experimental studies involving mechanical loading of the human head and brain in vivo are necessarily limited, making computational modeling essential for advancing our understanding of brain biomechanics. Demographic factors such as age and gender are known to influence brain anatomical structures, material properties, and potentially vulnerability to injurious loading. To address this, we construct six group-average brain models stratified by age and gender from a total of 135 subjects, and investigate the mechanical responses of these "group-average brains" using computational simulations. We use Pearson correlations to assess to what degree the group-average models represent individuals within each demographic category, showing strong correlations. Further, our p-value hypothesis test of the first principal strain across the six groups shows significant differences. This study demonstrates that age- and gender-stratified group-average models can effectively represent biomechanical responses of the individuals within the groups, and can reveal meaningful demographic differences that may influence susceptibility to traumatic brain injury. We show that the age-dependent change in material properties plays a greater role than anatomical changes in driving differences in the deformations. We hope to see increased utilization of these group-average models in both research and clinical applications.

Spinal cord injury (SCI) causes rapid and severe bone loss in the paralysed lower limbs, particularly at the distal femur and proximal tibia, where fragility fracture risk is high. In vitro nanoscale vibration at 1 kHz has been shown to promote osteogenic differentiation and inhibit osteoclastogenesis, suggesting potential as a targeted mechanical intervention. This study aimed to develop and evaluate a wearable device for delivering and monitoring localised nanovibration at the distal femur in individuals with SCI. The device delivered continuous sinusoidal nanoscale stimulation at 1 kHz via a bone-conduction transducer, with an opposing accelerometer used to monitor transmitted vibration in real time. Design and target-site selection were refined through two healthy-volunteer investigations comparing the distal femur, proximal tibia, and distal tibia. Bovine femur experiments characterised vibration transmission under controlled benchtop conditions. Preliminary repeated-use feasibility was assessed in one individual with motor-complete SCI. Healthy volunteer testing showed that although the ankle initially produced the highest transmitted amplitudes, these were highly variable, and positioning was inconsistent. Within the knee region, the distal femur provided the most practical and repeatable site for a wearable application. In bovine femur experiments, scanning laser vibrometry demonstrated measurable vibration on the condylar surface opposite the transducer, and depth-resolved measurements confirmed that nanoscale vibration remained detectable within bone. A gel interface layer reduced the transmitted amplitude. In the feasibility evaluation, 61 sessions were completed over 14 weeks, with logged accelerometry confirming repeated nanoscale vibration transmission. These findings establish feasibility and support further device optimisation and translational studies.

Silicones are elastomers that have a wide variety of uses, including biomedical applications such as the coating of biomedical devices and as implants. Soft silicones with mechanical properties similar to those of biological tissues have particularly gained use as substrates for cell culture in mechanobiology studies. In this context, it would be desirable to be able to alter their surface mechanical properties with a relatively simple physical treatment. While deep ultraviolet (deep UV) or ultraviolet C (UV-C) treatment has been previously used as a surface treatment method for stiffer silicones formulations, the effect of this treatment on soft silicones relevant for mechanobiology applications is still uncharacterized. We first used nanoindentation to determine the Youngs modulus of two types of soft silicones, Qgel and GEL-8100/Syl (GEL-8100 with Sylgard-184 crosslinker), both with initial moduli in the kilopascal range. We show that nanoindentation in the presence of 1% sodium dodecyl sulfate avoids adhesion between the nanoindentation glass probe and the soft silicones. After deep UV exposure in the presence of air, nanoindentation revealed that the apparent Youngs moduli of the soft silicones Qgel and GEL-8100/Syl increased by 70% and 33%, respectively. The bulk rheology of the soft silicones were not affected, suggesting that this corresponds to a surface stiffening effect with a topical stiffening of at least several hundred kilopascals. Energy-dispersive X-ray spectroscopy results show an increase in the mole fraction of oxygen, consistent with oxidation of the surface. Attenuated Total Reflectance Fourier-Transform Infrared spectra show evidence of Si-OH group formation in GEL-8100/Syl and silicon sub-oxide formation in Qgel. Consistent with this, water contact angle measurements show enhanced hydrophilicity after deep UV treatment. Our results have implications for using soft silicones as substrates in mechanobiology studies and in processes where deep UV light is used in the surface treatment of soft silicones.

Patellar osteochondral allograft (OCA) transplantation is widely used to treat large full-thickness cartilage defects, yet long-term failure and reoperation rates remain high. Although surface congruity and osseous integration are emphasized clinically, cartilage thickness and mechanical compatibility between donor and recipient are not considered. Our previous work suggests that cartilage thickness mismatch can amplify local deformation at the graft boundary, potentially compromising graft longevity. This study investigates how combined mismatches in cartilage thickness and mechanical properties influence the local strain environment at the patellar OCA interface. Simplified two-dimensional axisymmetric finite element models of patellar OCA repair were developed in ABAQUS. Donor-to-recipient cartilage thickness ratios ranging from 0.33 to 3.25 were evaluated together with donor-recipient Youngs modulus mismatches (2.5-7.0 MPa). Cartilage was modeled using homogeneous linear elastic and functionally graded material formulations to account for depth-dependent stiffness. A compressive pressure of 1.0 MPa was applied to represent patellofemoral joint loading, and peak compressive and shear strains were quantified at the graft boundary. Cartilage thickness mismatch produced localized high-strain regions (HSR) of compressive and shear strain at the donor-recipient interface that were absent in thickness-matched constructs. Strain amplification increased with both thickness and mechanical property mismatch. Compressive strain exhibited directional asymmetry, with donor-side-thicker configurations producing greater amplification than recipient-side-thicker configurations. Incorporating depth-dependent cartilage stiffness reduced peak strain magnitudes but did not eliminate mismatch-driven strain amplification. These findings demonstrate that cartilage thickness and mechanical disparity can create HSR at the patellar OCA graft boundary that may predispose grafts to impaired integration and long-term failure.

Identification and treatment of pregnancies at risk for preterm birth is a central challenge in obstetric research. Many of the known causes of preterm birth originate from mechanical failure in reproductive tissues. To better understand the biomechanical environment of the gravid uterus and its potential contribution to preterm birth, this computational study presents a parametric method for modeling maternal reproductive anatomy during the early second trimester. A finite element modeling approach was built using existing sonographic measurements from early second-trimester maternal anatomy and material properties from published mechanical tests. We applied the same physiologically relevant intrauterine pressure to all models and quantified the resulting tissue stretch. The sensitivity of the stretch in the proximal cervix was explored by varying material properties and sonographic maternal anatomy dimensions. Cervical material properties, particularly the fiber stiffness modulus and ground substance Youngs modulus, were found to have the greatest effect on proximal cervix stretch compared to other material properties and sonographic dimensions. Among the sonographic dimension measurements, those defining the region surrounding the proximal cervix had the greatest effect on proximal cervix stretch, including the curvature of the posterior uterine wall and the thickness of the lower uterine segment. The computational modeling approach presented here enables future patient-specific studies of gravid reproductive tissues to elucidate differences between individuals who do and do not deliver preterm. Additionally, this study is foundational for building digital twins to support future virtual clinical studies on diagnostic and therapeutic device design to prevent preterm birth.

Poly-L-Lysine (PLL) mediates the non-specific adhesion of cells and is commonly used in Atomic Force Microscopy (AFM) measurements, to ensure that cells remain attached to the substrate. However, it is acknowledged that adhesion affects the measured mechanical properties, in particular in the case Red Blood Cells (RBCs). This results in a wide range of Youngs modulus E reported in the literature. The present study aims at providing a systematic approach to the impact of non-specific adhesion on the rheology of RBCs. It provides a correlation between the topography profile of adherent RBCs and their rheology, from weak (cPLL = 10-3 mg/mL) to strong-adhesion (cPLL = 100 mg/mL) regimes. Using RICM and AFM, we find that there is a continuum of RBC shapes promoted by adhesion, from concave to dome-shaped, as predicted by the theory of vesicle adhesion. Their elastic properties discriminate them into two populations depending on adhesion strength, where stiffer RBCs (E {gtrsim} 100 Pa) correlate with dome-shaped cells. These findings are supported by rheology measurements of the dynamic complex shear modulus G*(f): while the storage modulus increases with cell-substrate adhesion, reflective of an increased membrane shear modulus, the loss modulus remains unchanged. Finally, further analysis inspired by membrane theory shows that different deformation modes may be triggered during indentation of either weakly or strongly adhering RBCs, illustrating the limits of the Hertz model.

Background Pulse-field ablation (PFA) is regarded as a non-thermal ablation modality, but there is an increasing range of complications that could be due to thermal effects. Methods The hydrogel undergoes permanent colour change when a target temperature is reached allowing direct visualisation of the surface thermal footprint and depth. Comparative lesion sets using a variable loop circular catheter (VP), circular over-the-wire catheter (PS) and pentaspline catheter (FP) were performed. Protocols included single and stacked applications with variation of force, irrigation, and voltage. The hydrogel lesions were analysed en-face and by section using digital image analysis. Results All 3 PFA catheters tested had significant thermal footprints. The VP catheter had the largest mean surface footprint (156.1mm2) and thermal depth (1.31mm) compared to the other two catheters (PS 55.4mm2 & 1.1mm, FP 29.8mm2 & 1.05mm, p<0.005). Increasing irrigation showed a trend to reduce thermal footprint but did not achieve statistical significance. Increasing voltage increased thermal footprint, but increasing force had negligible effect. Stacked lesions incrementally increased thermal lesion footprint and depth in all catheters. Thermal depths of up to 2.4mm were observed. Areas of darkening and degradation of the hydrogel were observed with the VP and FP catheters, consisting of up to 47% of lesion area. No darkening was observed with the PS catheter. Conclusions There are significant thermal footprints in all the systems tested. Temperatures exceeding 60oC have been demonstrated, comparable to radiofrequency ablation, and this may explain the mechanism of injury in some reports of collateral damage during PFA.

The aorta shows significant regional variation in geometry and composition. This complexity makes numerical modeling challenging, as it requires identifying material parameters. Typically, the Holzapfel-Gasser-Ogden model is used. However, it suffers from nonuniqueness and sensitivity to outliers, which can obscure biological variation. In addition, standard compressible formulations with a volumetric-isochoric split fail to couple volumetric and anisotropic responses. To address these issues, a regularized dual-estimation framework was introduced. This framework combines a global baseline estimator with local refinement while maintaining structural material continuity. Furthermore, it uses a Modified Anisotropic model to improve the representation of compressibility physics. For validation, the approach included uniaxial extension and protein quantification from Wistar rats. The results show that the proximal ascending/aortic-arch segment is most compliant at low stretch, whereas the abdominal aorta stiffens earlier and becomes fiber-dominated at lower stretch levels. Notably, these trends align directionally with regional composition. However, the fitted stress components are model-based descriptors rather than direct measurements of individual constituents.

The mechanical behavior of right ventricular (RV) myocardium is governed by its anisotropic microstructure, yet constitutive models that account for fiber dispersion and enable reliable parameter identification remain limited. In this study, we propose a physics-embedded constitutive neural network framework for automated discovery of strain energy functions and microstructural parameters from experimental data. The model is formulated within an incompressible, orthotropic hyperelastic setting using invariant-based representations. Fiber, sheet, and normal directions are incorporated through a rotated structural basis, and dispersion effects are modeled using a generalized structure tensor approach. The framework is trained on multi-axial mechanical data from ovine RV myocardium, including uniaxial tension-compression and simple shear tests. We investigate two training scenarios: (i) full datasets containing both tensile and compressive regimes and (ii) datasets restricted to tensile loading. In both cases, the model accurately reproduces the measured stress-strain responses and identifies sparse, interpretable constitutive models which involve isotropic, anisotropic, and coupling invariants. However, the identifiability of microstructural parameters strongly depends on the available loading conditions. While tensile-only data yield higher predictive accuracy, they result in non-unique or biased estimates of fiber dispersion. In contrast, inclusion of compressive data enables consistent identification of dispersion parameters by separating fiber and matrix contributions. These results highlight the importance of multi-axial loading data for robust parameter identification and demonstrate the capability of constitutive neural network-based approaches for data-driven modeling of anisotropic soft tissues.

Acute subdural hematoma (ASDH) is a prevalent injury with high mortality and morbidity, often resulting from bridging vein (BV) disruption secondary to cortical relative motion. As a thin membrane enveloping the brain surface and anchoring BVs, the pia mater is hypothesized to play a critical mechanical role in cortical response and hence ASDH pathogenesis. Finite element (FE) head models are valuable tools to predict ASDH occurrence during impacts. However, the pia mater is often represented as an elastic material in existing FE head models, despite experimental evidence reporting its nonlinear mechanical behavior. In this study, both linear (Young's modulus of 11.5 MPa) and nonlinear (the stress-strain curve derived from pial tension tests) material models of the pia mater were implemented in one FE head model. The models were subjected to three experimental impact loadings, one of which was known to cause ASDH and two of which were not. Results demonstrated that, across all simulated impacts, the model with nonlinear pia mater properties predicted larger cortical displacements and BV responses than the linear model. For the impact with known ASDH occurrence, the predicted BV strain was 0.17 for the nonlinear model and 0.094 for the linear model, with only the former approaching the reported rupture strain range of the BV-superior sagittal sinus complex (0.29 {+/-} 0.13). These findings verified the mechanical importance of the pia mater in cortical responses and hence the prediction of ASDH, suggesting that conventional linear pia modeling might over-constrain cortical motion, leading to underestimation of BV strain and ASDH risk. The current study supported the adoption of experimentally derived nonlinear pia mater properties in FE head models to improve the reliability of ASDH prediction.

PurposeComputational models of the uterus during pregnancy enable analysis of electro-chemo-mechanical pathways to predict labor timing and guide treatment planning. We aim to develop a robust image-based modeling pipeline to investigate uterine passive mechanics during late pregnancy. MethodsA parametric model of the uterus and cervix was created using a patients MRI measurements at 38 weeks of gestation. Inspired by advances in cardiac mechanics models, we created Laplace-Dirichlet solutions to inform tissue domains, fiber structure within the uterus and cervix, and spatially varying Robin boundary conditions. Prior imaging and mechanical testing data were used to fit material parameters. Boundary condition parameters were tuned to match the displacements of a previously established approach that employed contact with surrounding tissue. The tissue mechanical response to a physiologic load was assessed across varying material properties and fiber architectures. ResultsDiscrepancies in nodal displacements between the current approach and the contact-based model were limited to 3.4 {+/-} 1.8 mm, yielding nearly 90 % computational savings. Uterine tensile strains were more sensitive to ground substance elastic modulus (E) compared to fiber properties. Reduced E and fiber stiffness increased cervical strains and compression. Fiber dispersion and architecture modulated the opening of the cervical internal ostium but had a reduced impact on compression. ConclusionWe developed a novel workflow for modeling passive uterine mechanics, informed by patient-specific measurements and in vitro mechanical tests. The robust workflow may prove useful for studying labor progression and conducting longitudinal studies to enhance our understanding of normal and pathological pregnancies.

Relapse of aligned mandibular anterior teeth and the progressive collapse of the mandibular anterior arch are historically striking problems for orthodontists. The etiology of this collapse, and the cause of mesial molar drift, are unknown. However, light continuous (quasi-continuous) intra-oral pressures and forces applied to the mandibular dentition have been implicated. To explore this further, we use three-dimensional finite element analysis to investigate the influence of these intra-oral loads (tongue pressure, lip-cheek pressure, and interdental force) on mandibular arch collapse and mesial molar drift. Dentitions of three-dimensional finite element mandibular models were subjected to a wide range of simulated tongue pressures, lip-cheek pressures, and transseptal fiber-mediated interdental forces reported in the literature. Resulting crown displacement measurements from these isolated loads were made along with measurements resulting from simultaneous combined application of literature-defined mean tongue pressure, lip-cheek pressure, and interdental force. Our results indicate that tongue pressure alone results in generalized arch expansion and tooth spacing while lip-cheek pressure and interdental force result in generalized arch collapse, anterior crowding, and mesial molar displacement. Simultaneous application of tongue pressure, lip-cheek pressure, and interdental force mean values, as would occur in vivo, results in incisor crowding, intercanine width reduction, and mesial molar displacement. Our results suggest mandibular anterior arch collapse (incisor crowding / intercanine width reduction), and mesial molar displacement result from simultaneous application of tongue pressure, lip-cheek pressure, and interdental force.

The incidence of vascular complications differs among dermal filler formulations. This study aimed to evaluate the embolic risk associated with Neofilera(R), a filler composed of carboxymethyl cellulose and polylactic acid microspheres, following intra-arterial injection. The central auricular arteries of rabbits were injected with Neofilera(R) at volumes of 0.1 mL or 0.2 mL under various conditions: normal saline (control) and Neofilera(R) diluted at ratios of 1:5 (Group 1), 1:10 (Group 2), and 1:15 (Group 3). The presence of transparent emboli was assessed immediately after injection, while tissue necrosis (percentage and area) and histopathological alterations were evaluated on days 1 and 7 post-injection. Relative to controls, Neofilera(R) administered at 0.1 mL dispersed within minutes and did not induce significant tissue necrosis at either observation time point. In contrast, administration of 0.2 mL, even in diluted form, was associated with an increased incidence of vascular occlusion. Overall, these findings indicate that Neofilera(R) presents a lower embolic risk when injected at a volume of 0.1 mL, whereas higher injection volumes may substantially increase the likelihood of embolic complications.

In the current clinical practice, the diagnosis of spinal disorders and their surgical planning are critically based on imaging data. To complement this data, patient-specific finite element models have been developed and showed to be powerful tools for evaluating spine mechanics. Most of them rely on Computational Tomography (CT) scans - which have a high resolution but are seldom available in routine clinical practice - while only a recent few models are on less invasive Magnetic Resonance Imaging (MRI). Yet, despite the proliferation of these computational models, encompassing detailed anatomical and functional information, the rheological assumptions they are built upon are based on tissue-sample mechanical response data, which leaves a gap in the quantitative analysis on how such assumptions influence the macroscopic response of a functional spinal unit. Aiming at addressing these shortcomings, the main purpose of this work is to introduce a quantitative computational assessment of the macroscopic impact of commonly adopted rheological models - from linear elasticity to fiber-reinforced nonlinear hyperelasticity - in several loading conditions, focusing on a lumbar unit which is considered as a typical benchmark system. We also propose a reconstruction procedure to accurately describe subject-specific anatomy from MRI data, including the intervertebral disc and its nucleus pulposus. Bones are modeled as linear elastic media, whereas for the AF, we consider three different mechanical models - namely, isotropic linear elasticity and the Holzapfel-Gasser-Ogden model with and without fiber reinforcement. Model verification on an idealized geometry demonstrates numerical consistency, while parametric orthostatic simulations highlight the need for nonlinear formulations to capture anisotropy and strain-stiffening behavior of the intervertebral disc. Then, we carry out flexion, lateral bending, and torsion tests on a subject-specific reconstructed functional unit, for which we provide parametric analysis in terms of momentum magnitude and resulting range of motion. These tests further confirm the need for a nonlinear rheology of the annulus fibrosus and provide a quantitative assessment of the differences between the constitutive laws considered. Moreover, successful comparisons with the literature, in terms of macroscopic deformation under several loading conditions, serve as partial validation for our computational model.

The human spine is a complex, coordinated biomechanical system. Physiologically, its tissues are also highly interdependent in terms of function and viability. The interaction between mechanical stress and biological/biochemical activity over time constitutes a key driver of spinal degeneration. Research to date providing mechanistic insights into this process has focused on individual components (vertebra and disc tissue analogues), in isolation or as basic functional units. However, many observations from individual units will not translate to whole spine behaviour. The intricate complexity of the spine requires novel experimental models (synthetic and biotic), which must consider the spine at an organ level and adopt an integrative approach that can capture the dynamics which govern its function. Here, we report the development of a biomimetic spinal model prototype, amenable to cellular integration, which is miniaturised to the in vitro scale to provide a controlled environment and testbed for axial biological mechanics. The research presented here encompasses more than a decade of systematic investigations during which the gradual emergence of key manufacturing innovations progressively enabled addressing an exceptionally complex bioengineering challenge - organotypic spine engineering. The model comprises the full anatomical range of spinal vertebrae/bones (C1 to Sacrum & Coccyx), reproduced using bioceramic materials, assembled in sequence into a relevant columnar architecture and mechanically connected end-to-end by biochemically active interfaces. A range of assessments examining anatomical design, material behaviour and manufacturing processes is presented. The work explores concepts such as longitudinal mechanobiology and multi-segment coupling as well as manufacturing strategies using autonomous materials and instrumentation. This prototype introduces for the first time columnar level behaviour and the ability to study time dependent adaptations. This model is important because it can support tissue maturation, evolving mechanical properties and adaptive behaviour and it represents an intermediate step between isolated skeletal tissue models and future organ-level spinal constructs.