Effect of mechanical fatigue on commercial bioprosthetic TAVR valve mechanical and microstructural properties.

Valvular structural deterioration is of particular concern for transcatheter aortic valve replacements due to their suspected shorter longevity and increasing use in younger patient populations. In this work we investigated the mechanical and microstructural changes in commercial TAVR valves composed of both glutaraldehyde fixed bovine and porcine pericardium (GLBP and GLPP) following accelerated wear testing (AWT) as outlined in ISO 5840 standards. This provided greater physiological relevance to the loading compared to previous studies and by utilizing digital image correlation we were able to obtain strain contours for each leaflet pre and post fatigue and identify sites of fatigue damage. The areas of greatest change in mechanical strain for each leaflet were then further probed using biaxial tensile testing, confocal microscopy, and electron microscopy. It was observed that overall strain decreased in the GLPP valves following AWT of 200 million cycles while the GLBP valve showed an increase in overall strain. Biaxial tensile testing showed a statistically significant reduction in stress for GLPP while no significant changes were seen for GLBP. Both confocal and electron microscopy showed a disruption to the gross collagen organization and fibrillar structure, including fragmentation, for GLPP but only the former for GLBP. However, further test data is required to confirm these findings and to provide a better understanding of this fatigue pathway is required such that it can be incorporated into both valve design and selection processes to improve overall longevity for both GLPP and GLBP devices.

Automata, reason, and free will: Leibniz's critique of Descartes on animal and human nature.

This paper argues that Leibniz's use of the concept of "automaton" to characterize the nature of souls and bodies of living beings constitutes a systematic critique of Descartes' earlier use of automata. Whereas Descartes conceived non-human animals in terms of mechanical automata, he also denied that the human rational soul can be modeled on the nature of an automaton. In contrast, Leibniz understood living things to involve both an organic body, or "natural automaton," as well as an immaterial soul, or "spiritual automaton," that spontaneously produces its own perceptions. In extending the concept of the automaton to souls, Leibniz rejected key Cartesian assumptions about animals and free will and draws on the concept of the automaton to understand a range of cognitive capacities including volition. Leibniz thus occupies a distinctive place in the history of the use of automata to understand the nature of living things.

A direct comparison of the optically stimulated luminescent properties of BeO and Al2O3 for clinical in-vivo dosimetry.

Optically stimulated luminescence dosimetry is a relatively recent field of in-vivo dosimetry in clinical radiotherapy, developing over the last 20 years. As a pilot study, this paper presents a direct comparison between the sensitivity variance with use, stability of measurement and linearity of the current clinical standard Al2O3:C and a potential alternative, beryllium oxide. A set of ten optically stimulated luminescence dosimeters (OSLD), including five of each type, were used simultaneously and irradiated on a Versa HD linear accelerator. Having similar sensitivity, while Al2O3:C showed a relatively stable signal response from initial use, BeO was found to have a higher response to the same dose. However, BeO displayed a strong exponential decline from initial signal response following a model of [Formula: see text], reaching stability after approximately 10 irradiation cycles. BeO was shown to have potentially higher accuracy than Al2O3:C, with less variation between individual doses. Both OSLD showed good linearity between 0.2-5.0 Gy. Between these bounds, Al2O3:C demonstrated a strong linear response following the trend [Formula: see text], however beyond this showed deviation from linearity, resulting in a measured dose of [Formula: see text] Gy at 10.0 Gy dose delivery. BeO showed strong linearity across the full examined range of 0.2-10.0 Gy with following a model of [Formula: see text] Gy with a recorded dose at 10.0 Gy delivery as [Formula: see text] Gy. In conclusion, BeO does show large variance in sensitivity between individual OSLD and a considerable initial variance and decline in dose-response, however after pre-conditioning and individual normalisation to offset OSLD specific sensitivity BeO provides not only a viable alternative to Al2O3:C, but potentially provide higher accuracy, precision and reproducibility for in-vivo dosimetry.

Webinar and survey on quality management principles within the Australian and New Zealand ACPSEM Workforce.

Healthcare relies upon the accurate and safe delivery of patient care. This is only achievable when systems are developed to ensure high quality, robust outcomes, for instance quality management systems. The concept of quality management can take on a different meaning depending on the context in which it is found. To add complication, the amount of education required for quality management will vary depending on one's exposure to the implementation of quality systems. In part to address these issues, the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) Queensland Branch held a quality management webinar for members and non-members across Australia and New Zealand. The purpose of the webinar was to educate and facilitate discussion regarding the application of quality management principles for the ACPSEM profession. In conjunction, a pre- and post-webinar survey was conducted to gain an insight into existing knowledge and attitudes within the professions governed by the ACPSEM and students undertaking related studies. This paper authored by the webinar speakers reintroduces the quality management principles that were discussed in webinar, exemplifies the importance of quality management skills within the ACPSEM professions and presents the results of the surveys, promoting the need for more educational resources on quality management tools.

Evaluation of Pericardial Tissues from Assorted Species as a Tissue-Engineered Heart Valve Material.

Decellularized pericardial tissue is a strong candidate for a TEHV material as ECM is present to guide cellular infiltration and fixed porcine and bovine pericardial tissue have existing use in bioprosthetic heart valves. In this work, we compare the mechanical and microstructural properties of decellularized-sterilized (DS) porcine, bovine, and bison pericardial tissues with respect to use as a TEHV. H&E staining was used to verify removal of cellular content post-decellularization and to evaluate collagen fiber structure. Additionally, uniaxial and biaxial tension testing were used to compare mechanical performance and, for the latter, acquire constitutive model parameters for subsequent finite element (FE) modeling. H&E staining revealed complete removal of cellular content and good collagen fiber structure. Tensile testing showed comparable mechanical strength between the three DS pericardial tissues and considerably stronger mechanical properties compared to native tissues. Bovine and bison DS pericardial tissues showed the strongest mechanical performance in the FE models with bison demonstrating the overall best mechanical characteristics. The increased thickness of bovine and bison tissues coupled with the strong mechanical behavior and ECM structure indicates that these materials will be resistant to damage until sufficient cellular infiltration has occurred such that damaged tissue can be repaired.

Finite element analysis in clinical patients with atherosclerosis.

Endovascular plaque composition is strongly related to stent strut stress and is responsible for strut fatigue, stent failure, and possible in-stent restenosis. To evaluate the effect of plaque on artery wall resistance to expansion we performed in silico analysis of atherosclerotic vessels. We generated finite element models from in vivo intravascular ultrasound virtual histology images to determine local artery surface stiffness and determined which plaque structures have the greatest influence. We validated the predictive capacity of our modeling approach by testing an atherosclerotic peripheral artery ex vivo with pressure-inflation testing at physiological pressures ranging from 10 to 200 mmHg. For this purpose, the in silico deformation of the arterial wall was compared to that observed ex vivo. We found that calcification had a positive effect on surface stiffness with fibrous plaque and necrotic core having negative effects. Additionally, larger plaque structures demonstrated significantly higher average surface stiffness and calcification located nearer the lumen was also shown to increase surface stiffness. Therefore, more developed plaques will have greater resistance to expansion and higher stent strut stress, with calcification located near the lumen further increasing stress in localized areas. Thus, it may be expected that such plaque structures may increase the likelihood of localized stent strut fracture.

Experience of living with type 1 diabetes in a low-income country: a qualitative study from Liberia.

INTRODUCTION: While epidemiological data for type 1 diabetes (T1D) in low/middle-income countries, and particularly low-income countries (LICs) including Liberia is lacking, prevalence in LICs is thought to be increasing. T1D care in LICs is often impacted by challenges in diagnosis and management. These challenges, including misdiagnosis and access to insulin, can affect T1D outcomes and frequency of severe complications. Despite the severe nature of T1D and growing burden in sub-Saharan Africa, little is currently known about the impact of T1D on patients and caregivers in the region. METHODS: We conducted a qualitative study consisting of interviews with patients with T1D, caregivers, providers, civil society members and a policy-maker in Liberia to better understand the psychosocial and economic impact of living with T1D, knowledge of T1D and self-management, and barriers and facilitators for accessing T1D care. RESULTS: This study found T1D to have a major psychosocial and economic impact on patients and caregivers, who reported stigma, diabetes distress and food insecurity. Patients, caregivers and providers possessed the knowledge necessary to effectively manage T1D but insufficient community awareness leads to delayed diagnosis, often in an emergency department. Most patients reported receiving free services and materials, though the cost of transportation to clinic visits and recommended foods is a barrier to disease management. Many providers noted the lack of national T1D-specific guidelines and registries. Policy-makers reported a lack of prioritisation of and resources for T1D. These barriers, combined with scarcity and expense of appropriate foods, pose severe barriers for self-management of T1D. CONCLUSION: T1D was found to have a significant impact on patients and caregivers, and informants identified several key individual and systems-level barriers to effective T1D care in Liberia. Addressing these concerns is vital for designing sustainable and effective programmes for treating patients living with T1D.

Automatic Detection and Tracking of Marker Seeds Implanted in Prostate Cancer Patients using a Deep Learning Algorithm.

PURPOSE: Fiducial marker seeds are often used as a surrogate to identify and track the positioning of prostate volume in the treatment of prostate cancer. Tracking the movement of prostate seeds aids in minimizing the prescription dose spillage outside the target volume to reduce normal tissue complications. In this study, You Only Look Once (YOLO) v2™ (MathWorks™) convolutional neural network was employed to train ground truth datasets and develop a program in MATLAB that can visualize and detect the seeds on projection images obtained from kilovoltage (kV) X-ray volume imaging (XVI) panel (Elekta™). METHODS: As a proof of concept, a wax phantom containing three gold marker seeds was imaged, and kV XVI seed images were labeled and used as ground truth to train the model. The projection images were corrected for any panel shift using flex map data. Upon successful testing, labeled marker seeds and projection images of three patients were used to train a model to detect fiducial marker seeds. A software program was developed to display the projection images in real-time and predict the seeds using YOLO v2 and determine the centers of the marker seeds on each image. RESULTS: The fiducial marker seeds were successfully detected in 98% of images from all gantry angles; the variation in the position of the seed center was within ± 1 mm. The percentage difference between the ground truth and the detected seeds was within 3%. CONCLUSION: Our study shows that deep learning can be used to detect fiducial marker seeds in kV images in real time. This is an ongoing study, and work is underway to extend it to other sites for tracking moving structures with minimal effort.

Implementation outcomes of national decentralization of integrated outpatient services for severe non-communicable diseases to district hospitals in Rwanda.

OBJECTIVES: Effective coverage of non-communicable disease (NCD) care in sub-Saharan Africa remains low, with the majority of services still largely restricted to central referral centres. Between 2015 and 2017, the Rwandan Ministry of Health implemented a strategy to decentralise outpatient care for severe chronic NCDs, including type 1 diabetes, heart failure and severe hypertension, to rural first-level hospitals. This study describes the facility-level implementation outcomes of this strategy. METHODS: In 2014, the Ministry of Health trained two nurses in each of the country's 42 first-level hospitals to implement and deliver nurse-led, integrated, outpatient NCD clinics, which focused on severe NCDs. Post-intervention evaluation occurred via repeated cross-sectional surveys, informal interviews and routinely collected clinical data over two rounds of visits in 2015 and 2017. Implementation outcomes included fidelity, feasibility and penetration. RESULTS: By 2017, all NCD clinics were staffed by at least one NCD-trained nurse. Among the approximately 27 000 nationally enrolled patients, hypertension was the most common diagnosis (70%), followed by type 2 diabetes (19%), chronic respiratory disease (5%), type 1 diabetes (4%) and heart failure (2%). With the exception of warfarin and beta-blockers, national essential medicines were available at more than 70% of facilities. Clinicians adhered to clinical protocols at approximately 70% agreement with evaluators. CONCLUSION: The government of Rwanda was able to scale a nurse-led outpatient NCD programme to all first-level hospitals with good fidelity, feasibility and penetration as to expand access to care for severe NCDs.

A 3D printed phantom to assess MRI geometric distortion.

Geometric distortions in magnetic resonance can introduce significant uncertainties into applications such as radiotherapy treatment planning and need to be assessed as part of a comprehensive quality assurance program. We report the design, fabrication, and imaging of a custom 3D printed unibody MR distortion phantom along with quantitative image analysis.Methods: The internal cavity of the phantom is an orthogonal three-dimensional planar lattice, composed of 3 mm diameter rods spaced equidistantly at a 20 mm centre-centre offset repeating along the X, Y, and Z axes. The phantom featured an overall length of 308.5 mm, a width of 246 mm, and a height of 264 mm with lines on the external surface for phantom positioning matched to external lasers. The MR phantom was 3D printed in Nylon-12 using an advancement on traditional selective laser sintering (SLS) (HP Jet Fusion 3D-4200 machine). The phantom was scanned on a Toshiba Aquilion CT scanner to check the integrity of the 3D print and correct for any resultant issues. The phantom was then filled with NiSO4solution and scanned on a 3T PET-MR Siemens scanner for selected T1 and T2 sequences, from which distortion vectors were generated and analysed using in-house software written in Python.Results: All deviations of the node positions from the print design were less than 1 mm, with an average displacement of 0.228 mm. The majority of the deviations were smaller than the 0.692 mm pixel size for this dataset.Conclusion: A customised 3D printed MRI-phantom was successfully printed and tested for assessing geometric distortion on MRI scanners. 3D printed phantoms can be considered for clinics wishing to assess geometric distortions under specific conditions, but require resources for design, fabrication, commissioning, and verification.

Evaluation of the role of peripheral artery plaque geometry and composition on stent performance.

Peripheral stent fracture is a major precursor to restenosis of femoral artery atherosclerosis that has been treated with stent implantation. In this work, we validate a workflow for performing in silico stenting on a patient specific peripheral artery with heterogeneous plaque structure. Six human cadaveric femoral arteries were imaged ex vivo using intravascular ultrasound virtual histology (IVUS-VH) to obtain baseline vessel geometry and plaque structure. The vessels were then stented and the imaging repeated to obtain the stented vessel lumen area. Finite element (FE) models were then constructed using the IVUS-VH images, where the material property constants for each finite element were calculated using the proportions of each plaque component in the element, as identified by the IVUS-VH images. A virtual stent was deployed in each FE model, and the model lumen area was calculated and compared to the experimental lumen area to validate the modeling approach. The model was then used to compare stent performance for heterogeneous and homogeneous artery models, to determine whether plaque geometry or composition had added effects on stent performance. We found that the simulated lumen areas were similar to the corresponding experimental values, despite using generic material constants. Additionally, the heterogeneous and homogeneous lumen areas were also similar, implying that plaque geometry is a stronger predictor of stent expansion performance than plaque composition. Comparing stent stress and strain for heterogeneous and homogeneous models, it was found that stress from these two models had a strong linear correlation, while the strain correlation was weaker but still present. This implies that stent performance may be predicted with a simple homogeneous material models accounting for overall geometry of the plaque, providing that stent fatigue is calculated using stress criteria.

Crohn's disease in low and lower-middle income countries: A scoping review.

BACKGROUND: While Crohn's disease has been studied extensively in high-income countries, its epidemiology and care in low and lower-middle income countries (LLMICs) is not well established due to a lack of disease registries and diagnostic capacity. AIM: To describe the published burden, diagnostic/treatment capacity, service utilization, challenges/barriers to individuals with Crohn's in LLMICs and their providers. METHODS: We conducted a scoping review utilizing a full search strategy was developed and conducted in PubMed, Embase and World Health Organization Global Index Medicus. Two independent reviewers screened the titles and abstracts of all of the publications found in this search, reviewed selected publications, and extracted relevant data, which underwent descriptive review and was analyzed in Excel. RESULTS: The database search yielded 4486 publications, 216 of which were determined to be relevant to the research questions. Of all 79 LLMICs, only 21 (26.6%) have publications describing individuals with Crohn's. Overall, the highest number of studies came from India, followed by Tunisia, and Egypt. The mean number of Crohn's patients reported per study is 57.84 and the median is 22, with a wide range from one to 980. CONCLUSION: This scoping review has shown that, although there is a severe lack of population-based data about Crohn's in LLMICs, there is a signal of Crohn's in these settings around the world.

Noncommunicable Disease (NCD) strategic plans in low- and lower-middle income Sub-Saharan Africa: framing and policy response.

BACKGROUND: Global efforts to address NCDs focus primarily on 4-by-4 interventions - interventions to prevent and treat four groups of conditions affecting mainly older adults (some cardiovascular disease and cancers, type 2 diabetes, chronic respiratory disease) and four associated risk factors (alcohol, tobacco, poor diets, and physical inactivity). However, the NCD burden in Sub-Saharan Africa (SSA) is composed of a more diverse set of conditions, driven by a more complex group of risks, and impacting all segments of the population. OBJECTIVE: To document the NCD priorities identified by NCD strategic plans, to characterize the proposed policy response, and to assess the alignment between the two. METHODS: Using a two-part conceptual framework, we undertook a descriptive study to characterize the framing and overall policy response of strategic plans from 24 low- and lower-middle-income countries across SSA. RESULTS: The national situation assessments that ground strategic plans emphasize a diversity of conditions that range in terms of severity and frequency. These assessments also highlight a wide diversity of factors that shape this burden. Most include discussions of a broad range of behavioral, structural, genetic, and infectious risk factors. Plans endorse a more narrow response to this diverse burden, with a focus on primary and secondary prevention that is generally convergent with the objectives established in global policy documents. CONCLUSIONS: Broadly, we observe that plans developed by countries in SSA recognize the heterogeneity of the NCD burden in this region. However, they emphasize interventions that are consistent with global strategies focused on preventing a narrower set of cardiometabolic risk factors and their associated diseases. In comparison, relatively few countries detail plans to prevent, treat, and palliate the full scope of the needs they identify. There is a need for increased support for bottom-up planning efforts to address local priorities.

Chronic care service delivery models for people living with type 1 diabetes in low- and lower-middle income countries: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to map the published literature that describes the distribution and organization of chronic care service delivery models for people living with type 1 diabetes (PLWT1D) in low- and lower-middle-income countries (LLMICs). INTRODUCTION: Type 1 diabetes is an autoimmune condition commonly diagnosed in childhood and early adolescence; it cannot be prevented and is deadly without daily insulin injections. Among PLWT1D, the islet cells in the pancreas produce insufficient amounts of the glucose-regulating hormone, insulin, resulting in the need for chronic insulin replacement therapy. Epidemiological information regarding type 1 diabetes (T1D) is limited in LLMICs. Improving survival for PLWT1D in LLMICs requires early diagnosis and greater access to high quality chronic care service delivery models for T1D. The identification and reporting of service delivery model typologies for PLWT1D will allow for more specific research questions regarding individual typologies in subsequent systematic reviews. INCLUSION CRITERIA: The review will consider all types of literature on the organization and distribution of chronic care services for the management of PLWT1D provided out of facilities in LLMICs, published from 2000 to the present. METHODS: The JBI methodology for conducting scoping reviews will be employed. The search will be implemented across PubMed, Embase, and Web of Science. Full texts of the publications selected will be reviewed and data will be extracted through a charting table. The findings will be charted to summarize the results.

Ex Vivo Evaluation of IVUS-VH Imaging and the Role of Plaque Structure on Peripheral Artery Disease.

Peripheral artery disease (PAD) results from the buildup of atherosclerotic plaque in the arterial wall, can progress to severe ischemia and lead to tissue necrosis and limb amputation. We evaluated a means of assessing PAD mechanics ex vivo using ten human peripheral arteries with PAD. Pressure-inflation testing was performed at six physiological pressure intervals ranging from 10-200 mmHg. These vessels were imaged with IVUS-VH to determine plaque composition and change in vessel structure with pressure. Statistical analysis was performed to determine which plaque structures and distributions of these structures had the greatest influence on wall deformation. We found that fibrous plaque, necrotic core, and calcification had a statistically significant effect on all variables (p<0.05). The presence of large concentrations of fibrous plaque was linked to reduced vessel compliance and ellipticity, which could lead to stent fractures and restenosis. For the plaque distribution we found that clustered necrotic core increased overall compliance while clustered calcification decreased overall compliance. The effect of plaque distribution on vessel wall deformation must be considered equally important to plaque concentration.

Rate-Dependent and Relaxation Properties of Porcine Aortic Heart Valve Biomaterials.

OBJECTIVE: This work evaluates the rate-dependent and relaxation properties of native porcine heart valves, glutaraldehyde fixed porcine pericardium, and decellularized sterilized porcine pericardium. METHODS: Biaxial tension testing was performed at strain-rates of 0.001 s-1, 0.01 s-1, 0.1 s-1, and 1 s-1. Finally, relaxation testing for 300 s was performed on all heart valve biomaterials. RESULTS: No notable rate-dependent response was observed for any of the three biomaterials with few significant differences between any strain-rates. For relaxation testing, native tissues showed the most pronounced drop in stress and glutaraldehyde the lowest drop in stress although no tissues showed anisotropy in the relaxation. CONCLUSIONS: Increasing the strain-rate of the three biomaterials considered does not increase the stress within the tissue. This indicates that there will not be increased fatigue from accelerated wear testing compared to loading at physiological strain-rates as the increase strain-rates would likely not significantly alter the tissue stress.

Patient specific characterization of artery and plaque material properties in peripheral artery disease.

Patient-specific finite element (FE) modeling of atherosclerotic plaque is challenging, as there is limited information available clinically to characterize plaque components. This study proposes that for the limited data available in vivo, material properties of plaque and artery can be identified using inverse FE analysis and either a simple neo-Hookean constitutive model or assuming linear elasticity provides sufficient accuracy to capture the changes in vessel deformation, which is the available clinical metric. To test this, 10 human cadaveric femoral arteries were each pressurized ex vivo at 6 pressure levels, while intravascular ultrasound (IVUS) and virtual histology (VH) imaging were performed during controlled pull-back to determine vessel geometry and plaque structure. The VH images were then utilized to construct FE models with heterogeneous material properties corresponding to the vessel plaque components. The constitutive models were then fit to each plaque component by minimizing the difference between the experimental and the simulated geometry using the inverse FE method. Additionally, we further simplified the analysis by assuming the vessel wall had a homogeneous structure, i.e. lumping artery and plaque as one tissue. We found that for the heterogeneous wall structure, the simulated and experimental vessel geometries compared well when the fitted neo-Hookean parameters or elastic modulus, in the case of linear elasticity, were utilized. Furthermore, taking the median of these fitted parameters then inputting these as plaque component mechanical properties in the finite element simulation yielded differences between simulated and experimental geometries that were on average around 2% greater (1.30-5.55% error range to 2.33-11.71% error range). For the homogeneous wall structure the simulated and experimental wall geometries had an average difference of around 4% although when the difference was calculated using the median fitted value this difference was larger than for the heterogeneous fits. Finally, comparison to uniaxial tension data and to literature constitutive models also gave confidence to the suitability of this simplified approach for patient-specific arterial simulation based on data that may be acquired in the clinic.

Mechanical and finite element evaluation of a bioprinted scaffold following recellularization in a rat subcutaneous model.

Tissue engineered heart valves (TEHV) provide several advantages over currently available aortic heart valve replacements. Bioprinting provides a patient-specific means of developing a TEHV scaffold from imaging data, and the capability to embed the patient's own cells within the scaffold. In this work we investigated the remodeling capacity of a collagen-based bio-ink by implanting bioprinted disks in a rat subcutaneous model for 2, 4 and 12 weeks and evaluating the mechanical response using biaxial testing and subsequent finite element (FE) modeling. Samples explanted after 2 and 4 weeks showed inferior mechanical properties compared to native tissues while 12 week explants showed a mechanical response of similar magnitude but did not demonstrate the anisotropy present in native tissues. In the FE analysis, the model utilizing mechanical properties from samples explanted after 12 weeks showed the closest mechanical behavior to the native tissues. However, in diastole native tissues showed higher stress in the leaflet belly and lower strain at the commissures compared to 12 week explants, likely due to the anisotropy present in the native tissues. Thus, either further remodeling is required in situ in the aortic valve position or by in vitro preconditioning in an environment such as a bioreactor. Regardless, these results demonstrate the utility of FE analysis to optimize bioprinting process parameters for the most favorable in vivo mechanical performance.

Effect of cyclic deformation on xenogeneic heart valve biomaterials.

Glutaraldehyde-fixed bovine pericardium is currently the most popular biomaterial utilized in the creation of bioprosthetic heart valves. However, recent studies indicate that glutaraldehyde fixation results in calcification and structural valve deterioration, limiting the longevity of bioprosthetic heart valves. Additionally, glutaraldehyde fixation renders the tissue incompatible with constructive recipient cellular repopulation, remodeling and growth. Use of unfixed xenogeneic biomaterials devoid of antigenic burden has potential to overcome the limitations of current glutaraldehyde-fixed biomaterials. Heart valves undergo billion cycles of opening and closing throughout the patient's lifetime. Therefore, understanding the response of unfixed tissues to cyclic loading is crucial to these in a heart valve leaflet configuration. In this manuscript we quantify the effect of cyclic deformation on cycle dependent strain, structural, compositional and mechanical properties of fixed and unfixed tissues. Glutaraldehyde-fixed bovine pericardium underwent marked cyclic dependent strain, resulting from significant changes in structure, composition and mechanical function of the material. Conversely, unfixed bovine pericardium underwent minimal strain and maintained its structure, composition and mechanical integrity. This manuscript demonstrates that unfixed bovine pericardium can withstand cyclic deformations equivalent to 6 months of in vivo heart valve leaflet performance.

In Silico Performance of a Recellularized Tissue-Engineered Transcatheter Aortic Valve.

Commercially available heart valves have many limitations, such as a lack of remodeling, risk of calcification, and thromboembolic problems. Many state-of-the-art tissue-engineered heart valves (TEHV) rely on recellularization to allow remodeling and transition to mechanical behavior of native tissues. Current in vitro testing is insufficient in characterizing a soon-to-be living valve due to this change in mechanical response; thus, it is imperative to understand the performance of an in situ valve. However, due to the complex in vivo environment, this is difficult to accomplish. Finite element (FE) analysis has become a standard tool for modeling mechanical behavior of heart valves; yet, research to date has mostly focused on commercial valves. The purpose of this study has been to evaluate the mechanical behavior of a TEHV material before and after 6 months of implantation in a rat subdermis model. This model allows the recellularization and remodeling potential of the material to be assessed via a simple and inexpensive means prior to more complex ovine orthotropic studies. Biaxial testing was utilized to evaluate the mechanical properties, and subsequently, constitutive model parameters were fit to the data to allow mechanical performance to be evaluated via FE analysis of a full cardiac cycle. Maximum principal stresses and strains from the leaflets and commissures were then analyzed. The results of this study demonstrate that the explanted tissues had reduced mechanical strength compared to the implants but were similar to the native tissues. For the FE models, this trend was continued with similar mechanical behavior in explant and native tissue groups and less compliant behavior in implant tissues. Histology demonstrated recellularization and remodeling although remodeled collagen had no clear directionality. In conclusion, we observed successful recellularization and remodeling of the tissue giving confidence to our TEHV material; however, the mechanical response indicates the additional remodeling would likely occur in the aortic/pulmonary position.