Advancements in Finite Element Modeling for Cardiac Device Leads and 3D Heart Models.

The human heart's remarkable vitality necessitates a deep understanding of its mechanics, particularly concerning cardiac device leads. This paper presents advancements in finite element modeling for cardiac leads and 3D heart models, leveraging computational simulations to assess lead behavior over time. Through detailed modeling and meshing techniques, we accurately captured the complex interactions between leads and heart tissue. Material properties were assigned based on ASTM (American Society for Testing and Materials) standards and in vivo exposure data, ensuring realistic simulations. Our results demonstrate close agreement between experimental and simulated data for silicone insulation in pacemaker leads, with a mean force tolerance of 19.6 N ± 3.6 N, an ultimate tensile strength (UTS) of 6.3 MPa ± 1.15 MPa, and a percentage elongation of 125% ± 18.8%, highlighting the effectiveness of simulation in predicting lead performance. Similarly, for polyurethane insulation in ICD leads, we found a mean force of 65.87 N ± 7.1 N, a UTS of 10.7 MPa ± 1.15 MPa, and a percentage elongation of 259.3% ± 21.4%. Additionally, for polyurethane insulation in CRT leads, we observed a mean force of 53.3 N ± 2.06 N, a UTS of 22.11 MPa ± 0.85 MPa, and a percentage elongation of 251.6% ± 13.2%. Correlation analysis revealed strong relationships between mechanical properties, further validating the simulation models. Classification models constructed using both experimental and simulated data exhibited high discriminative ability, underscoring the reliability of simulation in analyzing lead behavior. These findings contribute to the ongoing efforts to improve cardiac device lead design and optimize patient outcomes.

In Vivo Durability of Polyurethane Insulated Implantable Cardioverter Defibrillator (ICD) Leads.

The 6935M Sprint Quattro Secure S and 6947M Sprint Quattro Secure are high voltage leads designed to administer a maximum of 40 joules of energy for terminating ventricular tachycardia or ventricular fibrillation. Both leads utilize silicone insulation and a polyurethane outer coating. The inner coil is shielded with polytetrafluoroethylene (PTFE) tubing, while other conductors are enveloped in ethylene tetrafluoroethylene (ETFE), contributing to the structural integrity and functionality of these leads. Polyurethane is a preferred material for the outer insulation of cardiac leads due to its flexibility and biocompatibility, while silicone rubber ensures chemical stability within the body, minimizing inflammatory or rejection responses. Thirteen implantable cardioverter defibrillator (ICD) leads were obtained from the Wright State University Anatomical Gift Program. The as-received devices exhibited varied in vivo implantation durations ranging from less than a month to 89 months, with an average in vivo duration of 41 ± 27 months. Tests were conducted using the Test Resources Q series system, ensuring compliance with ASTM Standard D 1708-02a and ASTM Standard D 412-06a. During testing, a load was applied to the intact lead, with careful inspection for surface defects before each test. Results of load to failure, percentage elongation, percentage elongation at 5 N, ultimate tensile strength, and modulus of elasticity were calculated. The findings revealed no significant differences in these parameters across all in vivo exposure durations. The residual properties of these ICD leads demonstrated remarkable stability and performance over a wide range of in vivo exposure durations, with no statistically significant degradation or performance changes observed.

Electromagnetic force from electric vehicles: Potential electromagnetic interference source for subcutaneous implantable defibrillator.

BACKGROUND: Electromagnetic interference (EMI) encompasses electromagnetic field signals that can be detected by a device's circuitry, potentially resulting in adverse effects such as inaccurate sensing, pacing, device mode switching, and defibrillation. EMI may impact the functioning of Cardiac Implantable Electronic Devices (CIEDs) and lead to inappropriate therapy. METHOD: An experimental measuring device, a loop antenna mimicking the implantable cardioverted defibrillator (ICD) antenna, was developed, and validated at the US Food and Drug Administration (FDA) and sent to Wright State University for testing. Two sets of measurements were conducted while the vehicle was connected to a 220-Volt outlet with charging at ON and OFF. Each measurement set involved three readings at various locations, with the antenna oriented in three different positions to account for diverse patient postures. The experiment utilized a Tesla Model 3 electric vehicle (EV), assessing scenarios both inside and outside the car, including the driver's seat, driver's seat floor, passenger's seat, rear seat, rear seat floor, cup holder, charging port (car), and near the charging station. RESULTS: The detected voltage (max 400 to 504 millivolts) around the cup holder inside the car differed from all other measurement scenarios. CONCLUSION: The investigation highlights the identification of EMI signals originating from an EV) that could potentially interrupt the functionality of a Subcutaneous Implantable Cardioverter-Defibrillator (S-ICD). These signals fell within the R-wave Spectrum of 30-300 Hz. Further in-vivo studies are essential to determine accurately the level of interference between S-ICDs and EMI from Electric Vehicles.

Mechanical Behavior of Polyurethane Insulation of CRT Leads in Cardiac Implantable Electronic Devices: A Comparative Analysis of In Vivo Exposure and Residual Properties.

Left ventricle leads are designed for the purpose of long-term pacing in the left ventricle. This study investigated the leads that use polyurethane as an outer insulator and SI-polyimide as an inner insulator. Polyurethane is commonly used for the outer insulation of cardiac leads due to its flexibility and biocompatibility. SI-polyimide (SI-PI) is a high-performance material known for its electrical insulation properties and is used for the inner insulation to maintain the integrity of the electrical pathways within the lead. Ten leads were received from the Wright State University Anatomical Gift Program. The duration of in vivo implantation varied for each lead, from less than a month to 108 months, with an average in vivo duration of 41 ± 31 months. We used the Test Resources Q series system for conducting our tests, as well as samples prepared to ensure compliance with the ASTM Standard D 1708-02a and the ASTM Standard D 412-06a. During the test, the load was applied to the intact lead. Before conducting individual tests, each lead was carefully inspected for surface defects. After conducting the tests, the load to failure, percentage of elongation, percentage of elongation at 5 N, ultimate tensile strength, and modulus of elasticity were calculated. There was no significant difference in load to failure, the percentage of elongation to failure, ultimate tensile strength, and modulus of elasticity (p-value = 0.82, p-value = 0.62, p-value = 0.82, and p-value = 0.12), respectively, when compared to in vivo exposure time. On the other hand, the percentage of elongation at 5 N force showed a significant difference (p-value = 0.0066) after 60 months in an in vivo environment. As the duration of in vivo exposure increased, the load to failure, percentage of elongation, ultimate tensile strength, and modulus of elasticity decreased insignificantly. The residual properties of these left ventricle leads remained relatively stable after 108 months of in vivo exposure duration, with no statistically significant degradation or changes in performance.

Investigation of a Deep Brain Stimulator (DBS) System.

A deep brain stimulator (DBS) device is a surgically implanted system that delivers electrical impulses to specific targets in the brain to treat abnormal movement disorders. A DBS is like a cardiac pacemaker, but instead of sending electrical signals to the heart, it sends them to the brain instead. When DBS leads and extension wires are exposed in the biological environment, this can adversely affect impedance and battery life, resulting in poor clinical outcomes. A posthumously extracted DBS device was evaluated using visual inspection and optical microscopy as well as electrical and mechanical tests to quantify the damage leading to its impairment. The implantable pulse generator (IPG) leads, a component of the DBS, contained cracks, delamination, exfoliations, and breakage. Some aspects of in vivo damage were observed in localized areas discussed in this paper. The duration of the time in months that the DBS was in vivo was estimated based on multiple regression analyses of mechanical property testing from prior research of pacemaker extensions. The test results of three DBS extensions, when applied to the regressions, were used to estimate the in vivo duration in months. This estimation approach may provide insight into how long the leads can function effectively before experiencing mechanical failure. Measurements of the extension coils demonstrated distortion and stretching, demonstrating the changes that may occur in vivo. These changes can alter the impedance and potentially reduce the effectiveness of the clinical treatment provided by the DBS system. Ultimately, as both DBSs and pacemakers use the same insulation and lead materials, the focus of this paper is to develop a proof of concept demonstrating that the mechanical properties measured from pacemaker extensions and leads extracted posthumously of known duration, measured in months while in vivo, can be used to predict the duration of DBS leads of unknown lifespan. The goal is to explore the validity of the proposed model using multiple regression of mechanical properties.

Anthropomorphic Characterization of Ankle Joint.

Even though total ankle replacement has emerged as an alternative treatment to arthrodesis, the long-term clinical results are unsatisfactory. Proper design of the ankle device is required to achieve successful arthroplasty results. Therefore, a quantitative knowledge of the ankle joint is necessary. In this pilot study, imaging data of 22 subjects (with both females and males and across three age groups) was used to measure the morphological parameters of the ankle joint. A total of 40 measurements were collected by creating sections in the sagittal and coronal planes for the tibia and talus. Statistical analyses were performed to compare genders, age groups, and image acquisition techniques used to generate 3D models. About 13 measurements derived for parameters (TiAL, SRTi, TaAL, SRTa, TiW, TaW, and TTL) that are very critical for the implant design showed significant differences (p-value < 0.05) between males and females. Young adults showed a significant difference (p-value < 0.05) compared to adults for 15 measurements related to critical tibial and talus parameters (TiAL, TiW, TML, TaAL, SRTa, TaW, and TTL), but no significant differences were observed between young adults and older adults, and between adults and older adults for most of the parameters. A positive correlation (r > 0.70) was observed between tibial and talar width values and between the sagittal radius values. When compared with morphological parameters obtained in this study, the sizes of current total ankle replacement devices can only fit a very limited group of people in this study. This pilot study contributes to the comprehensive understanding of the effects of gender and age group on ankle joint morphology and the relationship between tibial and talus parameters that can be used to plan and design ankle devices.

Traumatic Brain Injury Biomarkers, Simulations and Kinetics.

This paper reviews the predictive capabilities of blood-based biomarkers to quantify traumatic brain injury (TBI). Biomarkers for concussive conditions also known as mild, to moderate and severe TBI identified along with post-traumatic stress disorder (PTSD) and chronic traumatic encephalopathy (CTE) that occur due to repeated blows to the head during one's lifetime. Since the pathways of these biomarkers into the blood are not fully understood whether there is disruption in the blood-brain barrier (BBB) and the time it takes after injury for the expression of the biomarkers to be able to predict the injury effectively, there is a need to understand the protein biomarker structure and other physical properties. The injury events in terms of brain and mechanics are a result of external force with or without the shrapnel, in the wake of a wave result in local tissue damage. Thus, these mechanisms express specific biomarkers kinetics of which reaches half-life within a few hours after injury to few days. Therefore, there is a need to determine the concentration levels that follow injury. Even though current diagnostics linking biomarkers with TBI severity are not fully developed, there is a need to quantify protein structures and their viability after injury. This research was conducted to fully understand the structures of 12 biomarkers by performing molecular dynamics simulations involving atomic movement and energies of forming hydrogen bonds. Molecular dynamics software, NAMD and VMD were used to determine and compare the approximate thermodynamic stabilities of the biomarkers and their bonding energies. Five biomarkers used clinically were S100B, GFAP, UCHL1, NF-L and tau, the kinetics obtained from literature show that the concentration values abruptly change with time after injury. For a given protein length, associated number of hydrogen bonds and bond energy describe a lower bound region where proteins self-dissolve and do not have long enough half-life to be detected in the fluids. However, above this lower bound, involving higher number of bonds and energy, we hypothesize that biomarkers will be viable to disrupt the BBB and stay longer to be modeled for kinetics for diagnosis and therefore may help in the discoveries of new biomarkers.

Hierarchical Structure and Properties of the Bone at Nano Level.

Bone is a highly hierarchical complex structure that consists of organic and mineral components represented by collagen molecules (CM) and hydroxyapatite crystals (HAC), respectively. The nanostructure of bone can significantly affect its mechanical properties. There is a lack of understanding how collagen fibrils (CF) in different orientations may affect the mechanical properties of the bone. The objective of this study is to investigate the effect of interaction, orientation, and hydration on atomic models of the bone composed of collagen helix (CH) and HAC, using molecular dynamics simulations and therefrom bone-related disease origins. The results demonstrate that the mechanical properties of the bone are affected significantly by the orientation of the CF attributed to contact areas at 0° and 90° models. The molecular dynamics simulation illustrated that there is significant difference (p < 0.005) in the ultimate tensile strength and toughness with respect to the orientation of the hydrated and un-hydrated CF. Additionally, the results indicated that having the force in a longitudinal direction (0°) provides more strength compared with the CF in the perpendicular direction (90°). Furthermore, the results show that substituting glycine (GLY) with any other amino acid affects the mechanical properties and strength of the CH, collagen−hydroxyapatite interface, and eventually affects the HAC. Generally, hydration dramatically influences bone tissue elastic properties, and any change in the orientation or any abnormality in the atomic structure of either the CM or the HAC would be the main reason of the fragility in the bone, affecting bone pathology.

Design and Finite Element Analysis of Patient-Specific Total Temporomandibular Joint Implants.

In this manuscript, we discuss our approach to developing novel patient-specific total TMJ prostheses. Our unique patient-fitted designs based on medical images of the patient's TMJ offer accurate anatomical fit, and better fixation to host bone. Special features of the prostheses have potential to offer improved osseo-integration and durability of the devices. The design process is based on surgeon's requirements, feedback, and pre-surgical planning to ensure anatomically accurate and clinically viable device design. We use the validated methodology of FE modeling and analysis to evaluate the device design by investigating stress and strain profiles under functional/normal and para-functional/worst-case TMJ loading scenarios.

Biomechanical Evaluation of Recurrent Dissociation of Modular Humeral Prostheses.

The purpose of the study was to evaluate the force and torque required to dissociate a humeral head from the unimplanted modular total shoulder replacement system from different manufacturers and to determine if load and torque to dissociation are reduced in the presence of bodily fluids. Impingement, taper contamination, lack of compressive forces, and interference of taper fixation by the proximal humerus have all been reported as possible causes for dissociation. Experimental values determined in this research were compared with literature estimates of dissociation force of the humeral head under various conditions to gain more understanding of the causes of recurrent dissociations of the humeral head. This study examined biomechanical properties under dry and wet conditions under clinically practiced methods. Mean load to dissociation (1513 N ± 508 N) was found to be greater than that exerted by the activities of daily living (578 N) for all implants studied. The mean torque to dissociation was (49.77 N·m ± 19.07 N·m). Analysis of R2 correlation coefficients and p-values (α = 0.05) did not show any significant correlation between dry/bovine, dry/wet, or wet/bovine for load, displacement, or torsional stiffness in the majority of tests performed. Wetting the taper with water or bovine serum did not reduce the dissociation force to a statistically significant degree. Torque and lack of compressive forces at the rotator cuff may be the cause of dissociation at values less than those of activities of daily living. Torque data are provided by this study, but further research is needed to fully appreciate the role of torque in recurrent dissociations.

3D printed transwell-integrated nose-on-chip model to evaluate effects of air flow-induced mechanical stresses on mucous secretion.

While there are many chip models that simulate the air-tissue interface of the respiratory system, only a few represent the upper respiratory system. These chips are restricted to unidirectional flow patterns that are not comparable to the highly dynamic and variable flow patterns found in the native nasal cavity. Here we describe the development of a tunable nose-on-chip device that mimics the air-mucosa interface and is coupled to an air delivery system that simulates natural breathing patterns through the generation of bi-directional air flow. Additionally, we employ computational modeling to demonstrate how the device design can be tuned to replicate desired mechanical characteristics within specific regions of the human nasal cavity. We also demonstrate how to culture human nasal epithelial cell line RPMI 2650 within the lab-on-chip (LOC) device. Lastly, Alcian Blue histological staining was performed to label mucin proteins, which play important roles in mucous secretion. Our results revealed that dynamic flow conditions can increase mucous secretion for RPMI 2650 cells, when compared to no flow, or stationary, conditions.

Retrospective Evaluation and Framework Development of Bone Anisotropic Material Behavior Compared with Elastic, Elastic-Plastic, and Hyper-Elastic Properties.

The main motivation for studying damage in bone tissue is to better understand how damage develops in the bone tissue and how it progresses. Such knowledge may help in the surgical aspects of joint replacement, fracture fixation or establishing the fracture tolerance of bones to prevent injury. Currently, there are no standards that create a realistic bone model with anisotropic material properties, although several protocols have been suggested. This study seeks to retrospectively evaluate the damage of bone tissue with respect to patient demography including age, gender, race, body mass index (BMI), height, and weight, and their role in causing fracture. Investigators believe that properties derived from CT imaging data to estimate the material properties of bone tissue provides more realistic models. Quantifying and associating damage with in vivo conditions will provide the required information to develop mathematical equations and procedures to predict the premature failure and potentially mitigate problems before they begin. Creating a realistic model for bone tissue can predict the premature failure(s), provide preliminary results before getting the surgery, and optimize the design of orthopaedic implants. A comparison was performed between the proposed model and previous efforts, where they used elastic, hyper- elastic, or elastic-plastic properties. Results showed that there was a significant difference between the anisotropic material properties of bone when compared with unrealistic previous methods. The results showed that the density is 50% higher in male subjects than female subjects. Additionally, the results showed that the density is 47.91% higher in Black subjects than Mixed subjects, 53.27% higher than Caucasian subjects and 57.41% higher than Asian. In general, race should be considered during modeling implants or suggesting therapeutic techniques.

Biomechanical Behavior of a Variable Angle Locked Tibiotalocalcaneal Construct.

This paper examines the mechanics of the tibiotalocalcaneal construct made with a PHILOS plating system. A failed device consisting of the LCP plate and cortical, locking, and cannulated screws was used to perform the analysis. Visual, microstructure, and fractographic examinations were carried out to characterize the fracture surface topology. These examinations revealed the presence of surface scratching, inclusions, discoloration, corrosion pits, beach marks, and cleavage and striations on the fracture surface. Further examination of the material crystallography and texture revealed an interaction of S, Ni, and Mo-based inclusions that may have raised pitting susceptibility of the device made with Stainless Steel 316L. These features suggest that the device underwent damage by pitting the corrosion-fatigue mechanism and overloading towards the end to fail the plate and screws in two or more components. The screws failed via conjoint bending and torsion fatigue mechanisms. Computer simulations of variable angle locking screws were performed in this paper. The material of construction of the device was governed by ASTM F138-8 or its ISO equivalent 5832 and exhibited inconsistencies in chemistry and hardness requirements. The failure conditions were matched in finite element modeling and those boundary conditions discussed in this paper.

Cyclic Damage Accumulation in the Femoral Constructs Made With Cephalomedullary Nails.

Background: The purpose of this study was to evaluate the risk of peri-prosthetic fracture of constructs made with cephalomedullary (CM) long and short nails. The nails were made with titanium alloy (Ti-6Al-4V) and stainless steel (SS 316L). Methods: Biomechanical evaluation of CM nail constructs was carried out with regard to post-primary healing to determine the risk of peri-implant/peri-prosthetic fractures. Therefore, this research comprised of, non-fractured, twenty-eight pairs of cadaveric femora that were randomized and implanted with four types of fixation CM nails resulting in four groups. These constructs were cyclically tested in bi-axial mode for up to 30,000 cycles. All the samples were then loaded to failure to measure failure loads. Three frameworks were carried out through this investigation, Michaelis-Menten, phenomenological, and probabilistic Monte Carlo simulation to model and predict damage accumulation. Findings: Damage accumulation resulting from bi-axial cyclic loading in terms of construct stiffness was represented by Michaelis-Menten equation, and the statistical analysis demonstrated that one model can explain the damage accumulation during cyclic load for all four groups of constructs (P > 0.05). A two-stage stiffness drop was observed. The short stainless steel had a significantly higher average damage (0.94) than the short titanium nails (0.90, P < 0.05). Long titanium nail group did not differ substantially from the short stainless steel nails (P > 0.05). Results showed gender had a significant effect on load to failure in both torsional and bending tests (P < 0.05 and P < 0.001, respectively). Interpretation: Kaplan-Meier survival analysis supports the use of short titanium CM nail. We recommend that clinical decisions should take age and gender into consideration in the selection of implants.

Macrodamage Accumulation Model for a Human Femur.

The objective of this study was to more fully understand the mechanical behavior of bone tissue that is important to find an alternative material to be used as an implant and to develop an accurate model to predict the fracture of the bone. Predicting and preventing bone failure is an important area in orthopaedics. In this paper, the macrodamage accumulation models in the bone tissue have been investigated. Phenomenological models for bone damage have been discussed in detail. In addition, 3D finite element model of the femur prepared from imaging data with both cortical and trabecular structures is delineated using MIMICS and ANSYS® and simulated as a composite structure. The damage accumulation occurring during cyclic loading was analyzed for fatigue scenario. We found that the damage accumulates sooner in the multiaxial than in the uniaxial loading condition for the same number of cycles, and the failure starts in the cortical bone. The damage accumulation behavior seems to follow a three-stage growth: a primary phase, a secondary phase of damage growth marked by linear damage growth, and a tertiary phase that leads to failure. Finally, the stiffness of the composite bone comprising the cortical and trabecular bone was significantly different as expected.

Effect of Lipophilicity and Drug Ionization on Permeation Across Porcine Sublingual Mucosa.

Sublingual route is one of the oldest alternative routes studied for the administration of drugs. However, the effect of physical-chemical properties on drug permeation via this route has not been systemically investigated. The objective of this study was to determine the effect of two key physicochemical properties, lipophilicity and ionization, on the transport of drugs across porcine sublingual mucosa. A series of ß-blockers were used to study the effect of lipophilicity on drug permeation across the sublingual mucosa, while nimesulide (pKa 6.5) was used as a model drug to study the effect of degree of ionization on sublingual mucosa permeation of ionized and unionized species. Permeation of ß-blockers increased linearly with an increase in the lipophilicity for the range of compounds studied. The permeability of nimesulide across sublingual mucosa decreased with an increase of pH. The flux of ionized and unionized forms of nimesulide was determined to delineate the contribution of ionized and unionized species to the total flux. At low pH, the apparent flux was primarily contributed by unionized species; however, when the pH is increased beyond its pKa, the primary contributor to the apparent flux, nimesulide, is ionized species. The contribution of each species to the apparent flux was shown to be determined by the thermodynamic activity of ionized or unionized species. This study identified the roles of lipophilicity and thermodynamic activity in drug permeation across the sublingual mucosa. The findings can help guide the design of sublingual drug delivery systems with optimal pH and solubility.

An expert's opinion on what lies ahead in the field of alternative drug delivery.

Tarun Goswami speaks to Hannah Makin, Commissioning Editor: Tarun Goswami obtained his BS (Pharmacy) in 2003 from Delhi University (India) and his PhD in Pharmaceutical Sciences in 2008 from the University of the Pacific (CA, USA). He currently works at Amneal Pharmaceuticals as a Formulation Scientist in the Transdermal Drug Delivery Group. Having published multiple abstracts and articles in the area of transdermal and oral mucosal drug delivery, his current interests include the development of drug products that are administered via alternate routes such as through the skin and oral mucosa.

Role of pressure-sensitive adhesives in transdermal drug delivery systems.

Transdermal drug delivery systems (TDDS) are employed for the delivery of drugs across skin into the systemic circulation. Pressure-sensitive adhesive (PSA) is one of the most critical components used in a TDDS. The primary function of PSA is to help in adhesion of patch to skin, but more importantly it acts as a matrix for the drug and other excipients. Hence, apart from adhesion of the patch, PSA also affects other critical quality attributes of the TDDS such as drug delivery, flux through skin and physical and chemical stability of the finished product. This review article provides a summary of the adhesives used in various types of TDDS. In particular, this review will cover the design types of TDDS, categories of PSAs and their evaluation and regulatory aspects.

Chemistry, manufacturing and controls in passive transdermal drug delivery systems.

Transdermal drug delivery systems (TDDS) are used for the delivery of the drugs through the skin into the systemic circulation by applying them to the intact skin. The development of TDDS is a complex and multidisciplinary affair which involves identification of suitable drug, excipients and various other components. There have been numerous problems reported with respect to TDDS quality and performance. These problems can be reduced by appropriately addressing chemistry, manufacturing and controls requirements, which would thereby result in development of robust TDDS product and processes. This article provides recommendations on the chemistry, manufacturing and controls focusing on the unique technical aspects of TDDS.