The rupture of an atherosclerotic plaque cap overlying a lipid pool and/or necrotic core can lead to thrombotic cardiovascular events. In essence, the rupture of the plaque cap is a mechanical event, which occurs when the local stress exceeds the local tissue strength. However, due to inter- and intra-cap heterogeneity, the resulting ultimate cap strength varies, causing proper assessment of the plaque at risk of rupture to be lacking. Important players involved in tissue strength include the load-bearing collagenous matrix, macrophages, as major promoters of extracellular matrix degradation, and microcalcifications, deposits that can exacerbate local stress, increasing tissue propensity for rupture. This review summarizes the role of these components individually in tissue mechanics, along with the interplay between them. We argue that to be able to improve risk assessment, a better understanding of the effect of these individual components, as well as their reciprocal relationships on cap mechanics, is required. Finally, we discuss potential future steps, including a holistic multidisciplinary approach, multifactorial 3D in vitro model systems, and advancements in imaging techniques. The obtained knowledge will ultimately serve as input to help diagnose, prevent, and treat atherosclerotic cap rupture.
Introduction: Fibrocalcific remodeling is an end-stage feature of bioprosthetic (BP) structural valve degeneration and calcific aortic valve (AV) disease. However, the processes governing BP calcification are understudied. Here we conduct a histopathological assessment of BP degeneration in the aortic position and build a proteomic comparison map of BP degeneration versus AV disease in humans. Methods: Macroscopic segmentation was performed on entire explanted degenerated bovine pericardial BP leaflets (n=48) and diseased AV valves (n=19) and validated with histology to classify their state (BP: non-degenerated/thrombotic/neotissue/calcified, AV: non-diseased/fibrotic/calcified). Segment-specific bulk mass spectrometry-based proteomics was performed on BP/AV tissues. Laser capture microdissection enabled spatially resolved proteomics of BP calcification within discrete bioprosthetic/thrombotic/neotissue matrices versus explanted non-calcified regions. Results: Principal component analysis revealed BP and AV proteomes (2,005 and 2,012 proteins) clustered according to their degenerated and diseased segments; BP thrombotic and BP calcified sample clusters overlapped (Fig.A). Correlations of segment proteome-wide abundances revealed the highest intra-tissue similarity between non-degenerated BP and calcified BP (r p =0.87). The highest inter-tissue similarity was found between BP neotissue and calcified AV (r p =0.69) (Fig.B). Histopathological observations supported these proteomic findings, confirming the presence of calcification within discrete BP matrices: bioprosthetic (22/59), thrombus (22/59), and neotissue (15/59) (Fig.C). Laser capture microdissection revealed that 252 proteins were enriched in either bioprosthetic, thrombotic, or neotissue matrix calcification compared to explanted non-calcified regions. Only 3% of differentially enriched proteins overlapped, suggesting different mechanisms (Fig.D). Conclusions: This is the first comparative proteomic study of segmented degenerated BP and diseased AV tissue. We identified 3 subtypes of BP calcification within bioprosthetic, thrombotic, or neotissue matrices. Spatial proteomics revealed different proteins associated with the calcification of these matrices.
Thrombus computed tomography (CT) imaging characteristics may correspond with thrombus mechanical properties and thus predict thrombectomy success. The impact of red blood cell (RBC) content on these properties (imaging and mechanics) has been widely studied. However, the additional effect of platelets has not been considered. The objective of the current study was to examine the individual and combined effects of blood clot RBC and platelet content on resultant CT imaging and mechanical characteristics. Human blood clot analogues were prepared from a combination of preselected RBC volumes and platelet concentrations to decouple their contributions. The resulting clot RBC content (%) and platelet content (%) were determined using Martius Scarlet Blue and CD42b staining, respectively. Non-contrast and contrast-enhanced CT (NCCT and CECT) scans were performed to measure the clot densities. CECT density increase was taken as a proxy for clinical perviousness. Unconfined compressive mechanics were analysed by performing 10 cycles of 80% strain. RBC content is the major determinant of clot NCCT density. However, additional consideration of the platelet content improves the association. CECT density increase is influenced by clot platelet and not RBC content. Platelet content is the dominant component driving clot stiffness, especially at high strains. Both RBC and platelet content contribute to the clot's viscoelastic and plastic compressive properties. The current in vitro results suggest that CT density is reflective of RBC content and subsequent clot viscoelasticity and plasticity, and that perviousness reflects the clot's platelet content and subsequent stiffness. However, these indications should be confirmed in a clinical stroke cohort.
Background The purpose of this study was to validate a technique for measuring mean calcium density and to determine associations of cardiovascular risk factors with carotid calcium density. Methods and Results We performed a cross‐sectional study in a random sample of 100 stroke‐free participants from the population‐based Rotterdam Study. The mean calcium density of the combined left and right carotid bifurcations was quantified with a threshold of 130 Hounsfield Units (HU) using a novel density technique. To validate the methodology, carotid calcium volumes acquired using the technique in the current study were compared with measurements computed using dedicated clinical software (semiautomatic technique based on a threshold of ≥130 HU). Next, we investigated the associations of participant demographics, total calcium volume, and known cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, obesity, and smoking status) with the newly derived mean carotid calcium density measurement using linear regression analyses. Calcium volumes obtained with the 2 methods showed a high agreement (intraclass correlation coefficient=0.99, P <0.001), underlining the validity of the density technique. The total calcium volume was statistically significantly associated with the mean calcium density (cardiovascular risk factors adjusted model (B: 0.48 [95% CI, 0.30–0.66], P <0.001). We also found an association between hypercholesterolemia and mean calcium density (0.46 [0.09–0.83], P =0.017). No other significant associations were found between participant demographics or cardiovascular risk factors and mean carotid calcium density. Conclusions We demonstrated the feasibility of a carotid calcium density measurement technique. The data warrant a subsequent longitudinal study to determine the association between carotid calcium density and the risk of cerebrovascular events.
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.
Nanoparticles (NPs) represent an attractive strategy to overcome difficulties associated with the delivery of therapeutics. Knowing the optimal properties of NPs to address these issues could allow for improved in vivo responses. This work investigated NPs prepared from 5 materials of 3 sizes and 3 concentrations applied to a cell barrier model. The NPs permeability across a cell barrier and their effects on cell barrier integrity and cell viability were evaluated. The properties of these NPs, as determined in water (traditional) vs. media (realistic), were compared to cell responses. It was found that for all cellular activities, NP properties determined in media was the best predictor of the cell response. Notably, ZnO NPs caused significant alterations to cell viability across all 3 cell lines tested. Importantly, we report that the zeta potential of NPs correlates significantly with NP permeability and NP-induced changes in cell viability. NPs with physiological-based zeta potential of −12 mV result in good cell barrier penetration without considerable changes in cell viability.
Background Clot composition, contraction, and mechanical properties are likely determinants of endovascular thrombectomy success. A pre-interventional estimation of these properties is hypothesized to aid in selecting the most suitable treatment for different types of thrombi. Here we determined the association between the aforementioned properties and computed tomography (CT) characteristics using human blood clot analogues.Methods Clot analogues were prepared from the blood of 4 healthy human donors with 5 red blood cell (RBC) volume suspensions: 0%, 20%, 40%, 60% and 80% RBCs. Contraction was measured as the weight of the contracted clots as a percentage of the original suspension. The clots were imaged using CT with and without contrast to quantify clot density and density increase. Unconfined compression was performed to determine the high strain compressive stiffness. The RBC content was analysed using H&E staining.Results The 5 RBC suspensions formed only two groups of clots, fibrin-rich (0% RBCs) and RBC-rich (>90% RBCs), as determined by histology. The density of the fibrin-rich clots was significantly lower (31-38HU) compared to the RBC-rich clots (72-89HU), and the density increase of the fibrin-rich clots was significantly higher (82-127HU) compared to the RBC-rich clots (3-17HU). The compressive stiffness of the fibrin-rich clots was higher (178-1624 kPa) than the stiffness of the RBC-rich clots (6-526 kPa). Additionally, the degree of clot contraction was higher for the fibrin-rich clots (89-96%) compared to the RBC-rich clots (11-77%).Conclusions CT imaging clearly reflects clot RBC content and seems to be related to the clot contraction and stiffness. CT imaging might be a useful tool in predicting the thrombus characteristics. However, future studies should confirm these findings by analysing clots with intermediate RBC and platelet content.
Assessing the ability of pharmaceutics to cross biological barriers and reach the site-of-action requires faithful representation of these barriers in vitro. Difficulties have arisen in replicating in vivo resistance in vitro. This paper investigated serum starvation as a method to increase Caco-2 barrier stability and resistance. The effect of serum starvation on tight junction production was examined using transwell models; specifically, transendothelial electrical resistance (TEER), and the expression and localization of tight junction proteins, occludin and zonula occludens-1 (ZO-1), were studied using western blotting and immunofluorescence. Changing cells to serum-free media 2 days post-seeding resulted in TEER readings of nearly 5000 Ω cm2 but the TEER rapidly declined subsequently. Meanwhile, exchanging cells to serum-free media 4–6 days post-seeding produced barriers with resistance readings between 3000 and 4000 Ω cm2, which could be maintained for 18 days. This corresponded to an increase in occludin levels. Serum starvation as a means of barrier formation is simple, reproducible, and cost-effective. It could feasibly be implemented in a variety of pre-clinical pharmaceutical assessments of drug permeability across various biological barriers with the view to improving the clinical translation of novel therapeutics.
Background and aims: Atherosclerotic calcification is a powerful predictor of cardiovascular disease. This study aims to determine whether circulating levels of a local/systemic calcification inhibitor or a marker of bone formation correlate with measures of coronary or extracoronary calcification. Methods and results: Clinical computed tomography (CT) was performed on 64 arterial disease participants undergoing carotid and lower extremity endarterectomy. Coronary artery calcium (CAC) scores and volumes were acquired from the CT scans (n = 42). CAC scores and volumes were used to derive CAC density scores. Micro-CT was performed on excised carotid (n = 36) and lower extremity (n = 31) plaques to quantify the volume and volume fraction of extracoronary calcification. Circulating levels of dephospho-uncarboxylated Matrix Gla Protein (dpucMGP), fetuin-A, carboxylated and uncarboxylated osteocalcin (ucOC) were quantified using commercial immunoassays. Carotid participant CAC density scores were moderately negatively correlated with plasma dp-ucMGP (rs = -0.592, P = 0.008). A weak negative association was found between CAC scores and %ucOC for all participants (rs = -0.335, P = 0.040). Another weak negative correlation was observed between fetuin-A and the volume of calcification within
Acute ischemic stroke occurs when a thrombus obstructs a cerebral artery, leading to sub-optimal blood perfusion to brain tissue. A recently developed, preventive treatment is the endovascular stroke treatment (EVT), which is a minimally invasive procedure, involving the use of stent-retrievers and/or aspiration catheters. Despite its increasing use, many critical factors of EVT are not well understood. In this respect, in vitro, and in silico studies have the great potential to help us deepen our understanding of the procedure, perform further device and procedural optimization, and help in clinical training. This review paper provides an overview of the previous in vitro and in silico evaluations of EVT treatments, with a special emphasis on the four main aspects of the adopted experimental and numerical set-ups: vessel, thrombus, device, and procedural settings.
Thrombus composition and mechanical properties significantly impact the ease and outcomes of thrombectomy procedures in patients with acute ischemic stroke. A wide variation exists in the composition of thrombi between patients. If a relationship can be determined between the composition of a thrombus and its mechanical behaviour, as well as between the composition of a thrombus and its radiological imaging characteristics, then there is the potential to personalise thrombectomy treatment based on each individual thrombus. This review aims to give an overview of the current literature addressing this issue. Here, we present a scoping review detailing associations between thrombus composition, mechanical behaviour and radiological imaging characteristics. We conducted two searches 1) on the association between thrombus composition and the mechanical behaviour of the tissue and 2) on the association between radiological imaging characteristics and thrombus composition in the acute stroke setting. The review suggests that higher fibrin and lower red blood cell (RBC) content contribute to stiffer thrombi independent of the loading mode. Further, platelet-contracted thrombi are stiffer than non-contracted compositional counterparts. Fibrin content contributes to the elastic portion of viscoelastic behaviour while RBC content contributes to the viscous portion. It is possible to identify fibrin-rich or RBC-rich thrombi with computed tomography and magnetic resonance imaging vessel signs. Standardisation is required to quantify the association between thrombus density on non-contrast computed tomography and the RBC content. The characterisation of the thrombus fibrin network has not been addressed so far in radiological imaging but may be essential for the prediction of device-tissue interactions and distal thrombus embolization. The association between platelet-driven clot contraction and radiological imaging characteristics has not been explicitly investigated. However, evidence suggests that perviousness may be a marker of clot contraction.
Background: The Agatston Calcium Score is a predictor of major adverse cardiovascular events but it is unable to identify high-risk lesions. Recent research suggests that examining calcification phenotype could be more indicative of plaque stability. Objective: To examine the Agatston score's ability to determine atherosclerotic calcification phenotype. Methods: Micro-Computed Tomography was performed on 20 carotid and 20 peripheral lower limb lesions. ImageJ pixel histogram analysis quantified the non-calcified (>= 30HU, < 130HU) and calcified (>= 130HU) tissue volumes. ImageJ '3D Objects Counter' plugin determined the calcified particle count, volumes and maximum attenuation density of each particle. Image stacks were subsequently downsampled to a resolution of 0.7 x 0.7 x 3 mm and an approximation for the Extra-Coronary Calcium Scores (ECCS) were calculated. Spearman's correlation examined the relationships between ECCS approximations and calcification parameters. Results: ECCS has a strong positive correlation with the Calcified Volume Fraction (CVF) (r(s) = 0.865, p < 0.0005), weak positive correlations with Calcified Particle Fraction (CPF) (r(s) = 0.422, p = 0.007) and Microcalcification Fraction (micro-CF) (r(s) = 0.361, p = 0.022). There is no correlation evident between ECCS and Calcified Particle Index (CPI) (r(s) = - 0.162, p = 0.318). It is apparent that there is a high prevalence of microcalcifications in both carotid and peripheral lower limb lesions. Additionally, an inverse relationship exists between calcified particle volume and maximum-recorded attenuation density. Conclusion: The density-weighted Agatston calcium scoring methodology needs to be reviewed. Calcium scoring which differentiates between critical calcification morphologies, rather than presenting a density-weighted score, is required to direct high-risk plaques towards tailored treatment.
Background: A thorough understanding of cutting-edge geometry and cutting forces of hollow biopsy needles are required to optimise needle tip design to improve fine needle aspiration procedures. Objectives: To incorporate the dynamics of needle motion in a model for flexible hollow bevel tipped needle insertion into a biological mimetic soft-gel using parameters obtained from experimental work. Additionally, the models will be verified against corresponding needle insertion experiments. Methods: To verify simulation results, needle deflection and insertion forces were compared with corresponding experimental results acquired with an in-house developed needle insertion mechanical system. Additionally, contact stress distribution on needles from agar gel for various time scales were also studied. Results: For the 15 degrees, 30 degrees, 45 degrees, 60 degrees bevel angle needles, and 90 degrees blunt needle, the percentage error in needle deflection of each needle compared to experiments, were 7.3%, 9.9%, 8.6%, 7.8%, and 9.7% respectively. Varying the bevel angle at the needle tip demonstrates that the needle with a lower bevel angle produces the largest deflection, although the insertion force does not vary too much among the tested bevel angles. Conclusion: This experimentally verified computer-based simulation model could be used as an alternative tool for better understanding the needle-tissue interaction to optimise needle tip design towards improved biopsy efficiency.
The Coronary Artery Disease Reporting And Data System (CAD-RADS) and Coronary Artery Calcium Data and Reporting System (CAC-DRS) aim to improve communication of results.Images from 1,769 patients from the Scottish Computed Tomography of the HEART (SCOT-HEART) trial were assessed.Patients classifi ed as CAC-DRS 3 were at an increased risk of fatal or non-fatal myocardial infarction.Patients with higher CAD-RADS categories were at an increased risk of fatal or non-fatal myocardial infarction, with patients classifi ed as CAD-RADS 4B at the highest risk .This confi rms that the classifi cation provides additional prognostic discrimination for future coronary heart disease events.
Abstract The rupture of atherosclerotic plaques is the prerequisite for adverse cardiovascular events. Calcification morphology plays a critical role in plaque stability, therefore accurate calcification classification is essential for favourable patient management. Blood biomarkers may be a worthwhile approach to stratify patients based on calcification phenotype. Vitamin K-dependent Matrix γ-carboxyglutamate (Gla) protein (MGP) is a potent inhibitor of vascular calcification. Recent studies have demonstrated the potential utility of circulating non-functional MGP (dp-ucMGP) measurements to determine arterial stiffness and calcification levels. The objective of this study was to examine the relationship between circulating dp-ucMGP and calcification phenotype within symptomatic atherosclerotic lesions. Consenting patients undergoing standard endarterectomy procedures were recruited (n = 29). Fasting venous blood was collected preoperatively. Circulating plasma levels of dp-ucMGP were quantified using the inaKtif MGP (dp-ucMGP) iSYS kit. A bicinchoninic acid assay was used to standardise the total protein content present in each sample. High-resolution micro-CT imaging was conducted on the excised atherosclerotic specimens postoperatively. ImageJ post-processing was used to accurately quantify the calcification volume (≥ 130 Hounsfield Units) and determine the total number of calcified particles (3D objects counter plugin). Thirteen carotid (average age 71 years, 9 male) and fourteen peripheral lower limb (average age 65 years, 12 male) patients were examined. One patient had a carotid and a peripheral lower limb plaque (age 79, male). Peripheral lower limb specimens have larger volumes of calcification and higher numbers of calcified particles than carotid samples (472 ± 310 vs 85 ± 113mm3, p < 0.0005; 13919 ± 16034 vs 3476 ± 6208, p = 0.061.) While a higher dp-ucMGP value was noted in carotid than peripheral lower limb patients (214 ± 52 vs 169 ± 36pmol/L, p = 0.014) there was no correlation between circulating dp-ucMGP and calcification volume or number of calcified particles (rs = -0.329 and rs = 0.046). Previous research also found that peripheral lower limb lesions contain higher volumes of calcification than carotid lesions. There is currently no published data on calcified particle comparisons. Patients with symptomatic carotid disease are assumed to have a degree of peripheral arterial disease, this could explain the higher levels of circulating dp-ucMGP in carotid patients. The current study did not examine the dietary patterns of individuals with regards to Vitamin K intake or analyse other areas of the vasculature for additional calcification. This may interfere with dp-ucMGP measurements. This study serves as a preliminary investigation into the potential of dp-ucMGP as a blood based biomarker to distinguish between symptomatic atherosclerotic calcification phenotypes.
Introduction In professional rugby, sports-related concussion (SRC) remains the most frequent time loss injury. Therefore, accurately diagnosing SRC and monitoring player recovery, through a multi-modal assessment process, is critical to SRC management. In this protocol study, we aim to assess SRC over multiple time points post-injury to determine the value of multi-modal assessments to monitor player recovery. This is of significance to minimise premature return-to-play and, ultimately, to reduce the long-term effects associated with SRC. The study will also establish the logistics of implementing such a study in a professional setting to monitor a player’s SRC recovery.Methods and analysis All players from the participating professional rugby club within the Irish Rugby Football Union are invited to participate in the current study. Player assessment includes head injury assessment (HIA), neuropsychometric assessment (ImPACT), targeted biomarker analysis and untargeted biomarker analysis. Baseline HIA, ImPACT, and blood draws are performed prior to the start of playing season. During the baseline tests, player’s complete consent forms and an SRC history questionnaire. Subsequently, any participant that enters the HIA process over the playing season due to a suspected SRC will be clinically assessed (HIA and ImPACT) and their blood will be drawn within 3 days of injury, 6 days post-injury, and 13 days post-injury.Ethics and dissemination Ethical approval was attained from the Science and Engineering Research Ethics Committee, University of Limerick (Approval Code: 2018_06_11_S&E). On completion of the study, further manuscripts will be published to present the results of the tests and their ability to measure player recovery from SRC.Trial registration number NCT04485494.
Background and Purpose: The purpose of this study is to examine the ability of ex vivo derived Agatston, Volume, and Density-Volume calcium scores or calcium density measurements to differentiate between carotid plaques based on preoperative cerebrovascular symptomatology. Methods: Thirty-eight carotid plaques were acquired from standard endarterectomy. Micro-computed tomography was performed on the ex vivo samples. Image series were downsampled to represent the resolution of clinical multidetector computed tomography. Agatston, Volume, and Density-Volume carotid calcium scores were then calculated using coronary methodologies. The fractions of low- and high-density calcification were also determined. Results: The coronary calcium scores could not differentiate between carotid plaques from asymptomatic versus symptomatic patients. However, plaques from asymptomatic patients contained significantly lower fractions of low-density calcification and higher fractions of high-density calcification. Conclusions: Screening for carotid calcium density in noncontrast computed tomography could reflect plaque stability.
Biomechanical models predicting plaque rupture and device-tissue interactions rely on accurate material properties to produce reliable simulation results. However, there is a wide variation in the reported stiffness properties for advanced atherosclerotic lesions. The purpose of this study was to characterise isolated calcified and non-calcified portions of ex vivo carotid atherosclerotic tissues using nanomechanical techniques and compare the results against those from previous studies. Eleven carotid plaque samples were acquired from patients undergoing endarterectomy. Calcification was characterised using traditional instrumented indentation (TII) (n = 06). Micro-Computed Tomography was used to identify areas of calcification. Ferrule-top cantilever nanoindentation (FTC) was conducted on non-calcified tissue regions (n = 05). Adjacent tissue slices were stained with Alizarin Red to select regions of non-calcified tissue for testing. Scanning electron microscopy was employed to qualitatively assess the calcified and non-calcified samples’ surface roughness. The results from this study demonstrate over 6 orders of magnitude difference in stiffness between the elastic moduli of calcified (22.40 [17.70–27.55] GPa) and non-calcified (8.16 [3.85–14.78] kPa) carotid atherosclerotic tissues. Microscopy analysis indicates a larger variation in surface roughness produced with non-calcified tissue cryosectioning than with calcified tissue metallographic preparation, which may account for the increased amount of indent failures with FTC (32%) than with TII (11%). Performing high-resolution imaging and nanomechanical approaches in parallel produce results that clarify the wide range in reported properties for advanced atherosclerotic lesions. Future studies should examine the viscoelastic nature of diseased human arterial tissues.
Background: There is a lack of data on urethral injuries due to misplaced urinary catheters in paediatric patients. Our aim was to characterise the mechanical and histological features of juvenile porcine urethras after catheter-induced urethral trauma. We also propose the porcine model as being mechanically representative of a paediatric urethra. An understanding of paediatric urethral properties and their responses to catheter trauma is a vital foundation in preventing iatrogenic catheter-related injuries. Methods: Juvenile porcine urethras of varying ages (n=23, age: 2–7 months) were obtained from an abattoir to evaluate their mechanical and histological properties. The 7-month porcine model is representative of an adult urethra and corresponding testing was performed in adult embalmed cadavers (n=7) and a Thiel cadaver to correlate human relevance with this porcine model. Paediatric porcine urethras were mounted onto an experimental apparatus designed to measure pressure and diameter changes in response to catheter induced trauma. Eight-, 10- and 12-Fr silicone urinary catheters were inserted into the 2-, 3- and 7-month porcine urethral models respectively and the anchoring balloon was intentionally inflated in the bulbar urethra with the relevant recommended inflation volume. Results: Catheter balloon inflation pressures for 8-, 10- and 12-Fr urinary catheters were 198, 160, 284, 421 and 450 kPa in 2-, 3-, 7-month Thiel cadaver and embalmed cadaver respectively. On histological analysis, tearing and rupture of pediatric porcine urethra were observed following catheter balloon inflation with disruption of complete collagen, elastin and muscle fibres. Conclusions: Seven-month-old porcine urethra models approximate the mechanical properties of the cadaveric urethras. Conversely, 2- and 3-month porcine urethras provide significantly less “resistance to expansion” compared to the 7-month model. Therefore, young porcine models can represent the mechanical properties of pediatric urethral tissue in the context of catheter associated urethral trauma.