Patent ductus arteriosus (PDA) is a congenital defect characterized by abnormal blood flow between the aorta and pulmonary artery. Existing closure devices, such as the Amplatzer Duct Occluder (ADO), face challenges with affordability, biocompatibility, and anatomical adaptability. This study evaluates the safety and feasibility of a novel nitinol-based PDA occluder, the first developed sample in Iran, designed to enhance biocompatibility, reduce thrombogenicity, and improve durability. Methods: This preclinical study was conducted in 2024 at the Large Animal Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran. The occluder was fabricated from custom-made nitinol wires braided into a 72-wire conical mesh, ensuring flexibility and durability. Deployment was tested in a sheep model via femoral and pulmonary artery access. Post-procedure evaluations included angiography, clinical monitoring, and histopathological analyses to assess tissue integration, thrombogenicity, and biocompatibility. Results: The device was successfully deployed in two target sites with stable positioning and no procedural complications. Angiographic imaging confirmed vessel patency, even in an artery with a size mismatch. The animal exhibited no adverse outcomes, maintaining normal pulses and activity over a three-month follow-up. Post-mortem analysis revealed secure device placement without migration, perforation, or aneurysm. Histopathological findings demonstrated mild inflammation, neointimal formation, and re-endothelialization, with no significant thrombus or granuloma, indicating excellent biocompatibility. Conclusion: This study provides preliminary evidence supporting the feasibility, safety, and biocompatibility of the Iranian-developed PDA occluder. These findings suggest the device may serve as a viable, cost-effective alternative for PDA closure, addressing device shortages and advancing regional medical technology.

The fields of mechanobiology and biomechanics are expanding our understanding of the complex behavior of soft biological tissues across multiple scales. Given the intricate connection between tissue microstructure and its macroscale mechanical behavior, unraveling this mechanistic relationship remains an ongoing challenge. Reconstituted fiber networks serve as valuable in vitro models to simplify the intricacy of in vivo systems for targeted investigations. Concurrently, advances in imaging enable microstructure visualization and, through generative pipelines, modeling as discrete element networks. These mesoscale (μm) models provide insights into macroscale (mm) tissue behavior. However, there is still no clear way to systematically incorporate detailed experimentally observed microstructural changes into in silico models of biological networks. In this work, we develop a novel framework to generate topologically-driven discrete fiber networks using high-resolution images that account for how environmental changes during polymerization influence the resulting structure. Leveraging these networks, we generate models of interconnected load-bearing fiber components that exhibit softening under compression and are bending-resistant. The generative topology framework enables control over network-level features, such as fiber volume fraction and cross-link density, along with fiber-level properties, like length distribution, to simulate changes driven by different polymerization conditions. We validate the robustness of our simulations against experimental data in a collagen-specific study case where we examine nonlinear elastic responses of collagen networks across varying conditions. TopoGEN provides a versatile tool for tissue biomechanics and engineering, helping to bridge microstructural insights and bulk mechanical behavior by linking image-derived microstructural topological organization to soft tissue mechanics.

Endovascular thrombectomy (EVT) aims at restoring blood flow in case of acute ischemic stroke by removing the thrombus occluding a large cerebral artery. During the procedure with stent-retriever, the thrombus is captured within the device, which is then retrieved, subjecting the thrombus to several forces, potentially leading to its fragmentation. In silico studies, along with mechanical characterisation of thrombi, can enhance our understanding of the EVT, helping the development of new devices and interventional strategies. Our group previously validated a numerical approach to study EVT able to account for thrombus fragmentation. In this study, the same methodology was employed to explore the applicability of the chosen failure criterion to EVT simulations and the impact of thrombus composition on the outcome of the in silico procedure. For the first time, human clot analogues experimental data were applied to this methodology. Clot analogues of three different compositions were tested, and a material model incorporating failure was calibrated, followed by a verification analysis. Finally, the calibrated material model was used to perform EVT simulations, combining the three tested thrombus compositions with three different stent retriever models. The experimental tests confirmed a compression-tension asymmetry in the stress-strain curves, showing decreasing stiffness with increasing the red blood cell (RBC) content. Applying the resulting material models to EVT simulations demonstrated: (i) the dependency of the failure criterion on the thrombus mesh size, (ii) a greater tendency for RBC-rich thrombi to fragment, and (iii) increased difficulty in retrieving RBC-poor thrombi compared to RBC-rich thrombi.

This paper presents a computational study to investigate the mechanical properties of human penile tissues. Different experimental testing regimes, namely indentation and plate-compression tests, are compared to establish the most suitable testing regime for establishing the mechanical properties of the different penile tissues. An idealised MRI-based geometry of the penis, containing different tissue layers, is simulated using the finite element (FE) method to enable realistic predictions of the deformation of the penis. Unlike the linear elastic models used in the literature to-date, hyperelastic isotropic/anisotropic material models are used to capture material nonlinearity and anisotropy. The influence of material properties, morphological variations, material nonlinearity and anisotropy are investigated. Moreover, the implantation of an inflatable penile prosthesis (IPP) is simulated to assess the effects of the implantation procedure, material nonlinearity, and anisotropy on tissue stresses. The results indicate that the interior layers of the penis do not affect the overall stiffness of the penis in the indentation test, while the plate-compression test is able to capture the effects of these layers. Tunica Albuginea (TA) is found to have the most significant contribution to the total stiffness of the penis under load. It can also be observed that buckling occurs in the septum of the penis during the compression tests, and different morphologies dictate different compressive behaviours. There is a clear need for future experimental studies on penile tissues given the lack of relevant test data in the literature. Based on this study, plate-compression testing would offer the most insightful experimental data for such tissue characterisation.

Endovascular thrombectomy procedures are significantly influenced by the mechanical response of thrombi to the multi-axial loading imposed during retrieval. Compression tests are commonly used to determine compressive ex vivo thrombus and clot analogue stiffness. However, there is a shortage of data in tension. This study compares the tensile and compressive response of clot analogues made from the blood of healthy human donors in a range of compositions. Citrated whole blood was collected from six healthy human donors. Contracted and non-contracted fibrin clots, whole blood clots and clots reconstructed with a range of red blood cell (RBC) volumetric concentrations (5–80%) were prepared under static conditions. Both uniaxial tension and unconfined compression tests were performed using custom-built setups. Approximately linear nominal stress–strain profiles were found under tension, while strong strain-stiffening profiles were observed under compression. Low- and high-strain stiffness values were acquired by applying a linear fit to the initial and final 10% of the nominal stress–strain curves. Tensile stiffness values were approximately 15 times higher than low-strain compressive stiffness and 40 times lower than high-strain compressive stiffness values. Tensile stiffness decreased with an increasing RBC volume in the blood mixture. In contrast, high-strain compressive stiffness values increased from 0 to 10%, followed by a decrease from 20 to 80% RBC volumes. Furthermore, inter-donor differences were observed with up to 50% variation in the stiffness of whole blood clot analogues prepared in the same manner between healthy human donors.

INTRODUCTION: Erectile dysfunction (ED) affects to some degree approximately 52% of the male population aged 40-70 years. Many men do not respond to, or are precluded from using, pharmaceutical treatments for ED and are therefore advised to consider penile prostheses. Different types of penile prosthesis are available, such as inflatable penile prostheses (IPPs). IPPs consist of a pair of inflatable cylinders inserted into the corpora cavernosa (CC). During inflation/deflation of these cylinders, the CC and other surrounding tissues such as the tunica albuginea (TA) are highly impacted. Therefore, it is critical to understand the mechanics of penile tissues for successful implantation of IPPs and to reduce tissue damage induced by IPPs. OBJECTIVES: We explored the importance of the biomechanics of penile tissues for successful IPP function and reviewed and summarized the most significant studies on penile biomechanics that have been reported to date. METHODS: We performed an extensive literature review of publications on penile biomechanics and IPP implantation. RESULTS: Indenters have been used to characterize the mechanical behavior of whole penile tissue; however, this technique applied only local deformation, which limited insights into individual tissue components. Although one reported study addressed the mechanical behavior of TA, this investigation did not consider anisotropy, and there is a notable absence of biomechanical studies on CC and CS. This lack of understanding of penile tissue biomechanics has resulted in computational models that use linear-elastic materials, despite soft tissues generally exhibiting hyperelastic behavior. Furthermore, available benchtop/synthetic models do not have tissue properties matched to those of the human penis, limiting the scope of these models for use as preclinical testbeds for IPP testing. CONCLUSION: Improved understanding of penile tissue biomechanics would assist the development of realistic benchtop/synthetic and computational models enabling the long-term performance of IPPs to be better assessed.

Mechanical thrombectomy (MT) treatment of acute ischemic stroke (AIS) patients typically involves use of stent retrievers or aspiration catheters alone or in combination. For in silico trials of AIS patients, it is crucial to incorporate the possibility of thrombus fragmentation during the intervention. This study focuses on two aspects of the thrombectomy simulation: i) Thrombus fragmentation on the basis of a failure model calibrated with experimental tests on clot analogs; ii) the combined stent-retriever and aspiration catheter MT procedure is modeled by adding both the proximal balloon guide catheter and the distal access catheter. The adopted failure criterion is based on maximum principal stress threshold value. If elements of the thrombus exceed this criterion during the retrieval simulation, then they are deleted from the calculation. Comparison with in-vitro tests indicates that the simulation correctly reproduces the procedures predicting thrombus fragmentation in the case of red blood cells rich thrombi, whereas non-fragmentation is predicted for fibrin-rich thrombi. Modeling of balloon guide catheter prevents clot fragments' embolization to further distal territories during MT procedure.

Treatment of acute ischemic stroke has been recently improved with the introduction of endovascular mechanical thrombectomy, a minimally invasive procedure able to remove a clot using aspiration devices and/or stent-retrievers. Despite the promising and encouraging results, improvements to the procedure and to the stent design are the focus of the recent efforts. Computational studies can pave the road to these improvements, providing their ability to describe and accurately reproduce a real procedure. A patient with ischemic stroke due to intracranial large vessel occlusion was selected and after the creation of the cerebral vasculature from computed tomography images and a histologic analysis to determine the clot composition, the entire thrombectomy procedure was virtually replicated. As in the real situation, the computational replica showed that two attempts were necessary to remove the clot, as a result of the position of the stent retriever with respect to the clot. Furthermore, the results indicated that clot fragmentation did not occur as the deformations were mainly in a compressive state without the possibility for clot cracks to propagate. The accurate representation of the procedure can be used as an important step for operative optimization planning and future improvements of stent designs.

Background and Purpose: Mechanical properties of thromboemboli play an important role in the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke. However, very limited data on mechanical properties of human stroke thrombi are available. We aimed to mechanically characterize thrombi retrieved with EVT, and to assess the relationship between thrombus composition and thrombus stiffness. Methods: Forty-one thrombi from 19 patients with acute stroke who underwent EVT between July and October 2019 were mechanically analyzed, directly after EVT. We performed unconfined compression experiments and determined tangent modulus at 75% strain (E^t75) as a measure for thrombus stiffness. Thrombi were histologically analyzed for fibrin/platelets, erythrocytes, leukocytes, and platelets, and we assessed the relationship between histological components and E^t75with univariable and multivariable linear mixed regression. Results: Median E^t75was 560 (interquartile range, 393-1161) kPa. In the multivariable analysis, fibrin/platelets were associated with increased E^t75(aβ, 9 [95% CI, 5 to 13]) kPa, erythrocytes were associated with decreased E^t75%(aβ,-9 [95% CI,-5 to-13]) kPa. We found no association between leukocytes and E^t75. High platelet values were strongly associated with increased E^t75(aβ, 56 [95% CI, 38-73]). Conclusions: Fibrin/platelet content of thrombi retrieved with EVT for acute ischemic stroke is strongly associated with increased thrombus stiffness. For thrombi with high platelet values, there was a very strong relationship with thrombus stiffness. Our data provide a basis for future research on the development of next-generation EVT devices tailored to thrombus composition.