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.

The Mechanical Role of the Radial Fiber Network Within the Annulus Fibrosus of the Lumbar Intervertebral Disc: A Finite Elements Study.

The annulus fibrosus (AF) of the intervertebral disc (IVD) consists of a set of concentric layers composed of a primary circumferential collagen fibers arranged in an alternating oblique orientation. Moreover, there exists an additional secondary set of radial translamellar collagen fibers which connects the concentric layers, creating an interconnected fiber network. The aim of this study was to investigate the mechanical role of the radial fiber network. Toward that goal, a three-dimensional (3D) finite element model of the L3-L4 spinal segment was generated and calibrated to axial compression and pure moment loading. The AF model explicitly recognizes the two heterogeneous networks of fibers. The presence of radial fibers demonstrated a pronounced effect on the local disc responses under lateral bending, flexion, and extension modes. In these modes, the radial fibers were in a tensile state in the disc region that subjected to compression. In addition, the circumferential fibers, on the opposite side of the IVD, were also under tension. The local stress in the matrix was decreased in up to 9% in the radial fibers presence. This implies an active fiber network acting collectively to reduce the stresses and strains in the AF lamellae. Moreover, a reduction of 26.6% in the matrix sideways expansion was seen in the presence of the radial fibers near the neutral bending axis of the disc. The proposed biomechanical model provided a new insight into the mechanical role of the radial collagen fibers in the AF structure. This model can assist in the design of future IVD substitutes.

A New Growth Model for Aortic Valve Calcification.

Calcific aortic valve disease (CAVD) is a progressive disease in which minerals accumulate in the tissue of the aortic valve cusps, stiffening them and preventing valve opening and closing. The process of valve calcification was found to be similar to that of bone formation including cell differentiation to osteoblast-like cells. Studies have shown the contribution of high strains to calcification initiation and growth process acceleration. In this paper, a new strain-based calcification growth model is proposed. The model aims to explain the unique shape of the calcification and other disease characteristics. The calcification process was divided into two stages: Calcification initiation and calcification growth. The initiation locations were based on previously published findings and a reverse calcification technique (RCT), which uses computed tomography (CT) scans of patients to reveal the calcification initiation point. The calcification growth process was simulated by a finite element model of one aortic valve cusp loaded with cyclic loading. Similar to Wolff's law, describing bone response to stress, our model uses strains to drive calcification formation. The simulation grows calcification from its initiation point to its full typical stenotic shape. Study results showed that the model was able to reproduce the typical calcification growth pattern and shape, suggesting that strain is the main driving force behind calcification progression. The simulation also sheds light on other disease characteristics, such as calcification growth acceleration as the disease progresses, as well as sensitivity to hypertension.

Fluid-Structure Interaction Models of Bicuspid Aortic Valves: The Effects of Nonfused Cusp Angles.

Bicuspid aortic valve (BAV) is the most common type of congenital heart disease, occurring in 0.5-2% of the population, where the valve has only two rather than the three normal cusps. Valvular pathologies, such as aortic regurgitation and aortic stenosis, are associated with BAVs, thereby increasing the need for a better understanding of BAV kinematics and geometrical characteristics. The aim of this study is to investigate the influence of the nonfused cusp (NFC) angle in BAV type-1 configuration on the valve's structural and hemodynamic performance. Toward that goal, a parametric fluid-structure interaction (FSI) modeling approach of BAVs is presented. Four FSI models were generated with varying NFC angles between 120 deg and 180 deg. The FSI simulations were based on fully coupled structural and fluid dynamic solvers and corresponded to physiologic values, including the anisotropic hyper-elastic behavior of the tissue. The simulated angles led to different mechanical behavior, such as eccentric jet flow direction with a wider opening shape that was found for the smaller NFC angles, while a narrower opening orifice followed by increased jet flow velocity was observed for the larger NFC angles. Smaller NFC angles led to higher concentrated flow shear stress (FSS) on the NFC during peak systole, while higher maximal principal stresses were found in the raphe region during diastole. The proposed biomechanical models could explain the early failure of BAVs with decreased NFC angles, and suggests that a larger NFC angle is preferable in suture annuloplasty BAV repair surgery.

Unique Collagen Fibers for Biomedical Applications.

The challenge to develop grafts for tissue regeneration lies in the need to obtain a scaffold that will promote cell growth in order to form new tissue at a trauma-damaged site. Scaffolds also need to provide compatible mechanical properties that will support the new tissue and facilitate the desired physiological activity. Here, we used natural materials to develop a bio-composite made of unique collagen embedded in an alginate hydrogel material. The collagen fibers used to create the building blocks exhibited a unique hyper-elastic behavior similar to that of natural human tissue. The prominent mechanical properties, along with the support of cell adhesion affects cell shape and supports their proliferation, consequently facilitating the formation of a new tissue-like structure. The current study elaborates on these unique collagen fibers, focusing on their structure and biocompatibility, in an in vitro model. The findings suggest it as a highly appropriate material for biomedical applications. The promising in vitro results indicate that the distinctive collagen fibers could serve as a scaffold that can be adapted for tissue regeneration, in support of healing processes, along with maintaining tissue mechanical properties for the new regenerate tissue formation.

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.

Predictive Refined Computational Modeling of ACL Tear Injury Patterns.

Anterior cruciate ligament (ACL) ruptures are prevalent knee injuries, with approximately 200,000 ruptures annually, and treatment costs exceed USD two billion in the United States alone. Typically, the initial detection of ACL tears and anterior tibial laxity (ATL) involves manual assessments like the Lachman test, which examines anterior knee laxity. Partial ACL tears can go unnoticed if they minimally affect knee laxity; however, they will progress to a complete ACL tear requiring surgical treatment. In this study, a computational finite element model (FEM) of the knee joint was generated to investigate the effect of partial ACL tears under the Lachman test (GNRB® testing system) boundary conditions. The ACL was modeled as a hyperelastic composite structure with a refined representation of collagen bundles. Five different tear types (I-V), classified by location and size, were modeled to predict the relationship between tear size, location, and anterior tibial translation (ATT). The results demonstrated different levels of ATT that could not be manually detected. Type I tears demonstrated an almost linear increase in ATT, with the growth in tear size ranging from 3.7 mm to 4.2 mm, from 25% to 85%, respectively. Type II partial tears showed a less linear incline in ATT (3.85, 4.1, and 4.75 mm for 25%, 55%, and 85% partial tears, respectively). Types III, IV, and V maintained a nonlinear trend, with ATTs of 3.85 mm, 4.2 mm, and 4.95 mm for Type III, 3.85 mm, 4.25 mm, and 5.1 mm for Type IV, and 3.6 mm, 4.25 mm, and 5.3 mm for Type V, for 25%, 55%, and 85% partial tears, respectively. Therefore, for small tears (25%), knee stability was most affected when the tears were located around the center of the ligament. For moderate tears (55%), the effect on knee stability was the greatest for tears at the proximal half of the ACL. However, severe tears (85%) demonstrated considerable growth in knee instability from the distal to the proximal ends of the tissue, with a substantial increase in knee instability around the insertion sites. The proposed model can enhance the characterization of partial ACL tears, leading to more accurate preliminary diagnoses. It can aid in developing new techniques for repairing partially torn ACLs, potentially preventing more severe injuries.

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.

Fluid-structure interaction model of aortic valve with porcine-specific collagen fiber alignment in the cusps.

Native aortic valve cusps are composed of collagen fibers embedded in their layers. Each valve cusp has its own distinctive fiber alignment with varying orientations and sizes of its fiber bundles. However, prior mechanical behavior models have not been able to account for the valve-specific collagen fiber networks (CFN) or for their differences between the cusps. This study investigates the influence of this asymmetry on the hemodynamics by employing two fully coupled fluid-structure interaction (FSI) models, one with asymmetric-mapped CFN from measurements of porcine valve and the other with simplified-symmetric CFN. The FSI models are based on coupled structural and fluid dynamic solvers. The partitioned solver has nonconformal meshes and the flow is modeled by employing the Eulerian approach. The collagen in the CFNs, the surrounding elastin matrix, and the aortic sinus tissues have hyperelastic mechanical behavior. The coaptation is modeled with a master-slave contact algorithm. A full cardiac cycle is simulated by imposing the same physiological blood pressure at the upstream and downstream boundaries for both models. The mapped case showed highly asymmetric valve kinematics and hemodynamics even though there were only small differences between the opening areas and cardiac outputs of the two cases. The regions with a less dense fiber network are more prone to damage since they are subjected to higher principal stress in the tissues and a higher level of flow shear stress. This asymmetric flow leeward of the valve might damage not only the valve itself but also the ascending aorta.

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.

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.

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.

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.

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.

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.

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.

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.