Analysis of fibrocalcific aortic valve stenosis: computational pre-and-post TAVR haemodynamics behaviours.

Fibro-calcific aortic valve (AV) diseases are characterized by calcium growth or accumulation of fibrosis in the AV tissues. Fibrocalcific aortic stenosis (FAS) rises specifically in females, like calcification-induced aortic stenosis (CAS), may eventually necessitate valve replacement. Fluid-structure-interaction (FSI) computational models for severe CAS and FAS patients were developed using lattice Boltzmann method and multi-scale finite elements (FE). Three parametric AV models were introduced: pathology-free of non-calcified tri-and-bicuspid AVs with healthy collagen fibre network (CFN), a FAS model incorporated a thickened CFN with embedded small calcification volumes, and a CAS model employs healthy CFN with embedded high calcification volumes. The results indicate that the interaction between calcium deposits, adjacent tissue and fibres crucially influences haemodynamics and structural reactions. A fourth model of transcatheter aortic valve replacement (TAVR) post-procedure outcomes was created to study both CAS and FAS. TAVR-CAS had a higher maximum contact pressure and lower anchoring area than TAVR-FAS, making it prone to aortic tissue damage and migration. Finally, although the TAVR-CAS offered a larger opening area, its paravalvular leakage was higher. This may be attributed to a similar thrombogenicity potential characterizing both models. The computational framework emphasizes the significance of mechanobiology in FAS and underscores the requirement for tissue modelling at multiple scales.

Plant Biomimetic Principles of Multifunctional Soft Composite Development: A Synergistic Approach Enabling Shape Morphing and Mechanical Robustness.

Plant tissues are constructed as composite material systems of stiff cellulose microfibers reinforcing a soft matrix. Thus, they comprise smart and multifunctional structures that can change shape in response to external stimuli due to asymmetrical fiber alignment and possess robust mechanical properties. Herein, we demonstrate the biomimetics of the plant material system using silk fiber-reinforced alginate hydrogel matrix biocomposites. We fabricate single and bilamellar biocomposites with different fiber orientations. The mechanical behavior of the biocomposites is nonlinear, with large deformations, as in plant tissues. In general, the bilamellar system shows increased modulus, strain UTS, and toughness compared to the single-lamellar system for most of the tested orientations. Overall, the biocomposites present a wide range of elastic modulus values (3.0 ± 0.6-104.7 ± 11.3 MPa) and UTS values (0.23 ± 0.04-12.5 ± 2.0 MPa). The bilamellar biocomposites demonstrated shape-transforming abilities with diverse morphing modes, emulating different plant tissues and creating complex shape-morphing structures. These multifunctional biocomposites possess tunable and robust mechanical properties, controllable shape-morphing deformations, and the ability to self-controlled encapsulation, grip, and release objects. By harnessing biomimetic principles, these soft, smart, and multifunctional materials hold potential applications spanning from soft robotics, medicine, and tissue engineering to sensing and drug delivery.

Fluid-structure interaction modeling of compliant aortic valves using the lattice Boltzmann CFD and FEM methods.

The lattice Boltzmann method (LBM) has been increasingly used as a stand-alone CFD solver in various biomechanical applications. This study proposes a new fluid-structure interaction (FSI) co-modeling framework for the hemodynamic-structural analysis of compliant aortic valves. Toward that goal, two commercial software packages are integrated using the lattice Boltzmann (LBM) and finite element (FE) methods. The suitability of the LBM-FE hemodynamic FSI is examined in modeling healthy tricuspid and bicuspid aortic valves (TAV and BAV), respectively. In addition, a multi-scale structural approach that has been employed explicitly recognizes the heterogeneous leaflet tissues and differentiates between the collagen fiber network (CFN) embedded within the elastin matrix of the leaflets. The CFN multi-scale tissue model is inspired by monitoring the distribution of the collagen in 15 porcine leaflets. Different simulations have been examined, and structural stresses and resulting hemodynamics are analyzed. We found that LBM-FE FSI approach can produce good predictions for the flow and structural behaviors of TAV and BAV and correlates well with those reported in the literature. The multi-scale heterogeneous CFN tissue structural model enhances our understanding of the mechanical roles of the CFN and the elastin matrix behaviors. The importance of LBM-FE FSI also emerges in its ability to resolve local hemodynamic and structural behaviors. In particular, the diastolic fluctuating velocity phenomenon near the leaflets is explicitly predicted, providing vital information on the flow transient nature. The full closure of the contacting leaflets in BAV is also demonstrated. Accordingly, good structural kinematics and deformations are captured for the entire cardiac cycle.

Fragmentation of Different Calcification Growth Patterns in Bicuspid Valves During Balloon Valvuloplasty Procedure.

This study focuses on the calcification development and routes of type-1 bicuspid aortic valves based on CT scans and the effect of the unique geometrical shapes of calcium deposits on their fragmentation under balloon valvuloplasty procedures. Towards this goal, the novel Reverse Calcification Technique (RCT), which can predict the calcification progression leading to the current state based on CT scans, is utilized for n = 26 bicuspid aortic valves patients. Two main calcification patterns of type-1 bicuspid aortic valves were identified; asymmetric and symmetric with either partial or full arcs and circles. Subsequently, a calcification fragmentation biomechanical model was introduced to study the balloon valvuloplasty procedure prior to transcatheter aortic valve replacement implantation that allows better device expansion. To achieve this goal, six representative stenotic bicuspid aortic valves of different calcification patterns were investigated. It was found that the distinct geometrical shape of the calcium deposits had a significant effect on the cracks' initiations. Full or partial circle deposits had stronger resistance to fragmentation and mainly remained intact, yet, arc-shaped pattern deposits resulted in multiple cracks in bottleneck regions. The proposed biomechanical computational models could help assess calcification fragmentation patterns toward improving treatment approaches in stenotic bicuspid aortic valve patients, particularly for the off-label use of transcatheter aortic valve replacement.

Designing a Novel Asymmetric Transcatheter Aortic Valve for Stenotic Bicuspid Aortic Valves Using Patient-Specific Computational Modeling.

Bicuspid aortic valve (BAV), the most common congenital heart malformation, is characterized by the presence of only two valve leaflets with asymmetrical geometry, resulting in elliptical systolic opening. BAV often leads to early onset of calcific aortic stenosis (AS). Following the rapid expansion of transcatheter aortic valve replacement (TAVR), designed specifically for treating conventional tricuspid AS, BAV patients with AS were initially treated "off-label" with TAVR, which recently gained FDA and CE regulatory approval. Despite its increasing use in BAV, pathological BAV anatomy often leads to complications stemming from mismatched anatomical features. To mitigate these complications, a novel eccentric polymeric TAVR valve incorporating asymmetrical leaflets was designed specifically for BAV anatomies. Computational modeling was used to optimize its asymmetric leaflets for lower functional stresses and improved hemodynamic performance. Deployment and flow were simulated in patient-specific BAV models (n = 6) and compared to a current commercial TAVR valve (Evolut R 29 mm), to assess deployment and flow parameters. The novel eccentric BAV-dedicated valve demonstrated significant improvements in peak systolic orifice area, along with lower jet velocity and wall shear stress (WSS). This feasibility study demonstrates the clinical potential of the first known BAV-dedicated TAVR design, which will foster advancement of patient-dedicated valvular devices.

Validating In Silico and In Vitro Patient-Specific Structural and Flow Models with Transcatheter Bicuspid Aortic Valve Replacement Procedure.

INTRODUCTION: Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, which had been treated off-label by transcatheter aortic valve replacement (TAVR) procedure for several years, until its recent approval by the Food and Drug Administration (FDA) and Conformité Européenne (CE) to treat BAVs. Post-TAVR complications tend to get exacerbated in BAV patients due to their inherent aortic root pathologies. Globally, due to the paucity of randomized clinical trials, clinicians still favor surgical AVR as the primary treatment option for BAV patients. While this warrants longer term studies of TAVR outcomes in BAV patient cohorts, in vitro experiments and in silico computational modeling can be used to guide the surgical community in assessing the feasibility of TAVR in BAV patients. Our goal is to combine these techniques in order to create a modeling framework for optimizing pre-procedural planning and minimize post-procedural complications. MATERIALS AND METHODS: Patient-specific in silico models and 3D printed replicas of 3 BAV patients with different degrees of post-TAVR paravalvular leakage (PVL) were created. Patient-specific TAVR device deployment was modeled in silico and in vitro-following the clinical procedures performed in these patients. Computational fluid dynamics simulations and in vitro flow studies were performed in order to obtain the degrees of PVL in these models. RESULTS: PVL degree and locations were consistent with the clinical data. Cross-validation comparing the stent deformation and the flow parameters between the in silico and the in vitro models demonstrated good agreement. CONCLUSION: The current framework illustrates the potential of using simulations and 3D printed models for pre-TAVR planning and assessing post-TAVR complications in BAV patients.

The effect of the fibrocalcific pathological process on aortic valve stenosis in female patients: a finite element study.

Calcific aortic valve disease (CAVD) is the most common heart valvular disease in the developed world. Most of the relevant research has been sex-blind, ignoring sex-related biological variables and thus under-appreciate sex differences. However, females present pronounced fibrosis for the same aortic stenosis (AS) severity compared with males, who exhibit more calcification. Herein, we present a computational model of fibrocalcific AV, aiming to investigate its effect on AS development. A parametric study was conducted to explore the influence of the total collagen fiber volume and its architecture on the aortic valve area (AVA). Towards that goal, computational models were generated for three females with stenotic AVs and different volumes of calcium. We have tested the influence of fibrosis on various parameters as fiber architecture, fibrosis location, and transvalvular pressure. We found that increased fiber volume with a low calcium volume could actively contribute to AS and reduce the AVA similarly to high calcium volume. Thus, the computed AVAs for our fibrocalcific models were 0.94 and 0.84 cm2and the clinical (Echo) AVAs were 0.82 and 0.8 cm2. For the heavily calcified model, the computed AVA was 0.8 cm2and the clinical AVA was 0.73 cm2. The proposed models demonstrated how collagen thickening influence the fibrocalcific-AS process in female patients. These models can assist in the clinical decision-making process and treatment development in valve therapy for female patients.

A computational framework for post-TAVR cardiac conduction abnormality (CCA) risk assessment in patient-specific anatomy.

BACKGROUND: Cardiac conduction abnormality (CCA)- one of the major persistent complications associated with transcatheter aortic valve replacement (TAVR) may lead to permanent pacemaker implantation. Localized stresses exerted by the device frame on the membranous septum (MS) which lies between the aortic annulus and the bundle of His, may disturb the cardiac conduction and cause the resultant CCA. We hypothesize that the area-weighted average maximum principal logarithmic strain (AMPLS) in the MS region can predict the risk of CCA following TAVR. METHODS: Rigorous finite element-based analysis was conducted in two patients (Balloon expandable TAVR recipients) to assess post-TAVR CCA risk. Following the procedure one of the patients required permanent pacemaker (PPM) implantation while the other did not (control case). Patient-specific aortic root was modeled, MS was identified from the CT image, and the TAVR deployment was simulated. Mechanical factors in the MS region such as logarithmic strain, contact force, contact pressure, contact pressure index (CPI) and their time history during the TAVR deployment; and anatomical factors such as MS length, implantation depth, were analyzed. RESULTS: Maximum AMPLS (0.47 and 0.37, respectively), contact force (0.92 N and 0.72 N, respectively), and CPI (3.99 and 2.86, respectively) in the MS region were significantly elevated in the PPM patient as compared to control patient. CONCLUSION: Elevated stresses generated by TAVR devices during deployment appear to correlate with CCA risk, with AMPLS in the MS region emerging as a strong predictor that could be used for preprocedural planning in order to minimize CCA risk.

Assessment of Paravalvular Leak Severity and Thrombogenic Potential in Transcatheter Bicuspid Aortic Valve Replacements Using Patient-Specific Computational Modeling.

Bicuspid aortic valve (BAV), the most common congenital valvular abnormality, generates asymmetric flow patterns and increased stresses on the leaflets that expedite valvular calcification and structural degeneration. Recently adapted for use in BAV patients, TAVR demonstrates promising performance, but post-TAVR complications tend to get exacerbated due to BAV anatomical complexities. Utilizing patient-specific computational modeling, we address some of these complications. The degree and location of post-TAVR PVL was assessed, and the risk of flow-induced thrombogenicity was analyzed in 3 BAV patients - using older generation TAVR devices that were implanted in these patients, and compared them to the performance of the newest generation TAVR devices using in silico patient models. Significant decrease in PVL and thrombogenic potential was observed after implantation of the newest generation device. The current work demonstrates the potential of using simulations in pre-procedural planning to assess post-TAVR complications, and compare the performance of different devices to achieve better clinical outcomes. Patient-specific computational framework to assess post-transcatheter bicuspid aortic valve replacement paravalvular leakage and flow-induced thrombogenic complications and compare device performances.

Progressive Calcification in Bicuspid Valves: A Coupled Hemodynamics and Multiscale Structural Computations.

Bicuspid aortic valve (BAV) is the most common congenital heart disease. Calcific aortic valve disease (CAVD) accounts for the majority of aortic stenosis (AS) cases. Half of the patients diagnosed with AS have a BAV, which has an accelerated progression rate. This study aims to develop a computational modeling approach of both the calcification progression in BAV, and its biomechanical response incorporating fluid-structure interaction (FSI) simulations during the disease progression. The calcification is patient-specifically reconstructed from Micro-CT images of excised calcified BAV leaflets, and processed with a novel reverse calcification technique that predicts prior states of CAVD using a density-based criterion, resulting in a multilayered calcified structure. Four progressive multilayered calcified BAV models were generated: healthy, mild, moderate, and severe, and were modeled by FSI simulations during the full cardiac cycle. A valve apparatus model, composed of the excised calcified BAV leaflets, was tested in an in-vitro pulse duplicator, to validate the severe model. The healthy model was validated against echocardiography scans. Progressive AS was characterized by higher systolic jet flow velocities (2.08, 2.3, 3.37, and 3.85 m s-1), which induced intense vortices surrounding the jet, coupled with irregular recirculation backflow patterns that elevated viscous shear stresses on the leaflets. This study shed light on the fluid-structure mechanism that drives CAVD progression in BAV patients.

Nonlinear multiscale analysis of coronary atherosclerotic vulnerable plaque artery: fluid-structural modeling with micromechanics.

A unique three-dimensional (3D) computational multiscale modeling approach is proposed to investigate the influence of presence of microcalcification particles on the stress field distribution in the thin cap layer of a coronary atherosclerotic vulnerable plaque system. A nested 3D modeling analysis framework spanning the multiscale nature of a coronary atherosclerotic vulnerable plaque is presented. At the microscale level, a micromechanical modeling approach, which is based on computational finite-element (FE) representative unit cell, is applied to obtain the homogenized nonlinear response of the calcified tissue. This equivalent response effectively allows the integration of extremely small microcalcification inclusions in a global biomechanical FE model. Next, at the macroscale level, a 3D patient-based fluid-structure interaction FE model, reconstructing a refined coronary artery geometry with calcified plaque lesion, is generated to study the mechanical behavior of such multi-component biomechanical system. It is shown that the proposed multiscale modeling approach can generate a higher resolution of stress and strain field distributions within the coronary atherosclerotic vulnerable plaque system and allow the assessment of the local concentration stress around the microcalcifications in plaque cap layers. A comparison of stress field distributions within cap layers with and without inclusion of microcalcifications is also presented.

Bio-composites reinforced with unique coral collagen fibers: Towards biomimetic-based small diameter vascular grafts.

Cardiovascular Diseases (CVDs) are the leading cause of death worldwide. Approximately 31% of all global deaths are caused by CVDs, of which 42% are attributable to coronary artery disease (CAD). CAD is characterized by a narrowing of arteries that restricts the normal blood flow. Over time, surgical intervention is required in severe cases of occlusions and includes implantation of autologous vessels. Today synthetic grafts are used successfully as replacements for blood vessels with a diameter larger than 6 mm. However, they often fail as small-diameter blood vessel replacements. This study introduces a new biocomposite material system consisting of unique and long (cm-scale) collagen fibers derived from soft corals embedded within an alginate hydrogel matrix. The new biocomposite layers were used to fabricate grafts, towards developing a new class of tissue-engineered small-diameter blood vessels. These constructs consisted of both circumferentially and longitudinally oriented collagen fibers. The mechanical properties of the grafts were investigated via a new experimental setup constructed in our lab for this purpose, which applied internal pressure levels of 0-300 mmHg. Similar to native coronary arteries, the biocomposite tubes demonstrated a compliance of 4.88 ± 0.99%/100 mmHg for a physiologic pressure range of 80-120 mmHg. Furthermore, a numerical finite element simulation model is proposed to generate the overall mechanical response of the construct. It is composed of axial and circumferential fibers embedded within the continuum alginate elements. Good prediction is demonstrated when compared with the measured pressure-strain response. Moreover, we examined biocompatibility and cell growth on the collagen fibers. Fibroblast cells proliferated during the experiment that lasted for 32 days and showed aligned configuration with the collagen fiber orientation. The novelty of this study is manifested in the use of naturally derived coral-based long collagen fibers for the development of a new class of tissue-engineered grafts. The proposed novel biocomposite graft demonstrated both mechanical and biological compatibility and can be further developed for small-diameter blood-vessel replacement.

Structural Responses of Integrated Parametric Aortic Valve in an Electro-Mechanical Full Heart Model.

The aortic valve (AV) is located between the left ventricle and the aorta and responsible for maintaining an outward unidirectional flow. Many AV hemodynamic and structural aspects of have been extensively studied, however, more sophisticated models are needed to better understand the AV biomechanical behavior. This study deals with integrating a new parametric AV structural model with the electro-mechanical Living Heart Human Model® (LHHM). The LHHM is a finite element model simulating human heart capable of realistic electro-mechanical simulations. Different geometric metrics of AV have been examined. New integrated structural AV model within the LHHM better predict local stresses during the cardiac cycle due to the realistic boundary condition derived from the LHHM. It was found that ellipticity index (EI), calculated as the ratio between the maximal (Max) and minimal (Min) aortic annulus (AA) diameters, well correlates with measured clinical data obtained from patients undergoing computed tomography (CT) while the annular perimeter (Perim) matches the same trend. This increases the confidence in the predicted kinematic behavior, leaflets coaptation, and the overall stresses. From the clinical aspect, the new proposed coupled and integrated AV modeling can serve as a platform for design and implementation of pre-transcatheter aortic valve replacement (TAVR) procedures.

Coral-Derived Collagen Fibers for Engineering Aligned Tissues.

There is a growing need for biomaterial scaffolds that support engineering of soft tissue substitutes featuring structure and mechanical properties similar to those of the native tissue. This work introduces a new biomaterial system that is based on centimeter-long collagen fibers extracted from Sarcophyton soft corals, wrapped around frames to create aligned fiber arrays. The collagen arrays displayed hyperelastic and viscoelastic mechanical properties that resembled those of collagenous-rich tissues. Cytotoxicity tests demonstrated that the collagen arrays were nontoxic to fibroblast cells. In addition, fibroblast cells seeded on the collagen arrays demonstrated spreading and increased growth for up to 40 days, and their orientation followed that of the aligned fibers. The possibility to combine the collagen cellular arrays with poly(ethylene glycol) diacrylate (PEG-DA) hydrogel, to create integrated biocomposites, was also demonstrated. This study showed that coral collagen fibers in combination with a hydrogel can support biological tissue-like growth, with predefined orientation over a long period of time in culture. As such, it is an attractive scaffold for the construction of various engineered tissues to match their native oriented morphology.

Finite strain parametric HFGMC micromechanics of soft tissues.

A micromechanical analysis is offered for the prediction of the global behavior of biological tissues. The analysis is based on the isotropic-hyperelastic behavior of the individual constituents (Collagen and Elastin), their volume fractions, and takes into account their detailed interactions. The present analysis predicts the instantaneous tensors from which the effective current first tangent tensor is established, thus providing the overall anisotropic constitutive behavior of the composite and the resulting field distribution in the composite. This is in contradistinction with the macroanalysis in which the composite internal energy, which involves unknown functions that depend on several strain invariants, must be proposed. The offered micromechanical analysis forms a generalization to the finite strain high-fidelity generalized method of cells (HFGMC) based on the homogenization technique for periodic composites to the parametric finite strain. This involves an arbitrary discretization of the repeating unit-cell of the periodic composites. Results are given for the response of the human abdominal aorta, which consists of three layered tissues: intima, media, and adventitia, all of which are composed out of the Collagen and Elastin. The isotropic-hyperelastic constituents (Mooney-Rivlin and Yeoh) of the composites are calibrated by utilizing available experimental data which describe the response of the tissue. Validation of the results is performed by comparison of the predicted Cauchy stress and stretches with the experimental measurements. In addition, results are given in the form of Cauchy stress and deformation gradient field distributions in the constituents of several tissues.

The Effect of Localized Vibration during Welding on the Microstructure and Mechanical Behavior of Steel Welds.

The use of vibratory welding is treated with some caution in the industry due to inconsistent beneficiary results. Here, a partial explanation is suggested by the differentiation between global vibrational effects (GVEs) and local vibrational effects (LVEs), and the latter is investigated experimentally. Two structural plates of steel are welded at three frequency/amplitude combinations using manual gas metal arc welding in an experimental setup that ensures only LVEs. After welding, tensile tests, microhardness tests, and metallurgical characterization are performed locally in the different welding zones and the results are compared to the non-vibrated welds. Novel use of digital image correlation (DIC) is implemented in tensile testing of welded samples, thus enabling the separate determination of local mechanical properties of the base metal, heat-affected zone and fusion zone of the same weld. LVE is found not to promote any distinct difference in weld properties, at least within the vibrational regimes studied. Nevertheless, depending on geometry and structural response, it is explained how vibratory welding may promote residual stress relief due to GVEs of the welded structure.

Biomechanical modeling of transcatheter aortic valve replacement in a stenotic bicuspid aortic valve: deployments and paravalvular leakage.

Calcific aortic valve disease (CAVD) is characterized by stiffened aortic valve leaflets. Bicuspid aortic valve (BAV) is the most common congenital heart disease. Transcatheter aortic valve replacement (TAVR) is a treatment approach for CAVD where a stent with mounted bioprosthetic valve is deployed on the stenotic valve. Performing TAVR in calcified BAV patients may be associated with post-procedural complications due to the BAV asymmetrical structure. This study aims to develop refined computational models simulating the deployments of Evolut R and PRO TAVR devices in a representative calcified BAV. The paravalvular leakage (PVL) was also calculated by computational fluid dynamics simulations. Computed tomography scan of severely stenotic BAV patient was acquired. The 3D calcium deposits were generated and embedded inside a parametric model of the BAV. Deployments of the Evolut R and PRO inside the calcified BAV were simulated in five bioprosthesis leaflet orientations. The hypothesis of asymmetric and elliptic stent deployment was confirmed. Positioning the bioprosthesis commissures aligned with the native commissures yielded the lowest PVL (15.7 vs. 29.5 mL/beat). The Evolut PRO reduced the PVL in half compared with the Evolut R (15.7 vs. 28.7 mL/beat). The proposed biomechanical computational model could optimize future TAVR treatment in BAV patients. Graphical abstract.

A patient specific computational biomechanical model for the entire lumbosacral spinal unit with imposed spondylolysis.

BACKGROUND: A biomechanical model of the lumbosacral spinal unit between L1-S1 was developed to investigate the behavior of normal and select pathological states. Our aims were to generate predictive structural models for mechanical deformation including critical stresses in the spine components and to investigate the probability of subsequent lumbar spine fractures in the presence of unilateral spondylolysis. METHODS: A non-linear three-dimensional finite element pathology-free model of the L1-S1 lumbosacral unit was generated using patient-specific computerized tomography scans and calibrated by comparing it to experimental data of a range of motion modes consisting of flexion, extension, left and right lateral bending, and left and right axial rotation. Unilateral and bilateral pars defects were created on the isthmus of L5 to simulate spondylolysis. FINDINGS: Results showed that under flexion, left lateral bending and right axial rotation, stresses were higher on the contralateral L5 pars-interarticularis, whereas, no significant changes occurred on the left-right isthmus of the L2-L4 and S1. Significant changes in the range of motion compared to the pathology-free model were observed in bilateral spondylolysis not only adjacent to the pars defect area but also in other lumbar spine levels. INTERPRETATION: The proposed pathology-free lumbosacral unit model showed good correlation with experimental tests for all loading cases. In unilateral spondylolysis, a subsequent pars defect was observed within the same vertebra. The overall modeling approach can be used to study different pathological states.

Towards intervertebral disc engineering: Bio-mimetics of form and function of the annulus fibrosus lamellae.

The aging western society is heavily afflicted with intervertebral disc (IVD) degeneration. Replacement or repair of the degenerated IVD with an artificial bio-mimetic construct is one of the challenges of future research due to its complex structure and unique biomechanical function. Herein, biocomposite laminates made of long collagen fibers in unidirectional (-1.3 ±â€¯2.1°) and angle-plied ±â€¯30° orientations (30.4 ±â€¯6.4 and -29.8 ±â€¯4.5), embedded in alginate hydrogel, were fabricated to mimic the form of single annulus fibrosus (AF) lamella and the circumferential AF, respectively. The mechanical behavior of the composites was measured and compared with in vitro existing data of the human native AF as well as with new data obtained from ovine and bovine specimens. The mechanical behavior was found to reproduce the full stress- strain behavior of the human AF single lamella in several regions of the AF and the Young's modulus was 28.3 ±â€¯8.6 MPa. Moreover, the modulus of the angle-plied laminates was 16.8 ±â€¯2.9 MPa, which is approximately 5% less than the in vitro data. The full stress-strain behavior was also compared with bovine and ovine circumferential AF samples and found to be very similar, with a difference in the modulus of 4.1% and 19.7%, respectively. Moreover, an FE model of the L3-L4 functional spinal unit (FSU) was developed and calibrated to evaluate the mechanical ability of the biocomposite to be used as an AF substitute under physiological IVD loading modes. The biocomposite demonstrated a good ability to mimic the stiffness of the native tissue under physiologic loading modes as flexion, extension, lateral bending and compression, but was too flexible under torsion. It was found that the proposed biomimetics AF design resulted in a compatible function in several mechanical levels, which holds great potential to be used as a viable AF replacement towards full IVD engineering.