Characterization of primary human leptomeningeal cells in 2D culture.

Maintaining the integrity of brain barriers is critical for a healthy central nervous system. While extensive research has focused on the blood-brain barrier (BBB) of the brain vasculature and blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus, the barriers formed by the meninges have not received as much attention. These membranes create a barrier between the brain and cerebrospinal fluid (CSF), as well as between CSF and blood. Recent studies have revealed that this barrier has been implicated in the development of neurological and immunological disorders. In order to gain a deeper comprehension of the functioning and significance of the meningeal barriers, sophisticated models of these barriers, need to be created. The aim of this paper is to investigate the characteristics of commercially available primary leptomeningeal cells (LMCs) that form the meningeal barriers, in a cultured environment, including their morphology, proteomics, and barrier properties, and to determine whether passaging of these cells affects their behaviour in comparison to their in vivo state. The results indicate that higher passage numbers significantly alter the morphology and protein localisation and expression of the LMCs. Furthermore, the primary cell culture co-stained for S100A6 and E-cadherin suggesting it is a co-culture of both pial and arachnoid cells. Additionally, cultured LMCs showed an increase in vimentin and cytokeratin expression and a lack of junctional proteins localisation on the cell membrane, which could suggest loss of epithelial properties due to culture, preventing barrier formation. This study shows that the LMCs may be a co-culture of pial and arachnoid cells, that the optimal LMC passage range is between passages two and five for experimentation and that the primary human LMCs form a weak barrier when in culture.

Microindentation of fresh soft biological tissue: A rapid tissue sectioning and mounting protocol.

Microindentation of fresh biological tissues is necessary for the creation of 3D biomimetic models that accurately represent the native extracellular matrix microenvironment. However, tissue must first be precisely sectioned into slices. Challenges exist in the preparation of fresh tissue slices, as they can tear easily and must be processed rapidly in order to mitigate tissue degradation. In this study, we propose an optimised mounting condition for microindentation and demonstrate that embedding tissue in a mixture of 2.5% agarose and 1.5% gelatin is the most favourable method of tissue slice mounting for microindentation. This protocol allows for rapid processing of fresh biological tissue and is applicable to a variety of tissue types.

Region-Specific Phosphorylation Determines Neuroligin-3 Localization to Excitatory Versus Inhibitory Synapses.

BACKGROUND: Neuroligin-3 is a postsynaptic adhesion molecule involved in synapse development and function. It is implicated in rare, monogenic forms of autism, and its shedding is critical to the tumor microenvironment of gliomas. While other members of the neuroligin family exhibit synapse-type specificity in localization and function through distinct interactions with postsynaptic scaffold proteins, the specificity of neuroligin-3 synaptic localization remains largely unknown. METHODS: We investigated the synaptic localization of neuroligin-3 across regions in mouse and human brain samples after validating antibody specificity in knockout animals. We raised a phospho-specific neuroligin antibody and used phosphoproteomics, cell-based assays, and in utero CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9) knockout and gene replacement to identify mechanisms that regulate neuroligin-3 localization to distinct synapse types. RESULTS: Neuroligin-3 exhibits region-dependent synapse specificity, largely localizing to excitatory synapses in cortical regions and inhibitory synapses in subcortical regions of the brain in both mice and humans. We identified specific phosphorylation of cortical neuroligin-3 at a key binding site for recruitment to inhibitory synapses, while subcortical neuroligin-3 remained unphosphorylated. In vitro, phosphomimetic mutation of that site disrupted neuroligin-3 association with the inhibitory postsynaptic scaffolding protein gephyrin. In vivo, phosphomimetic mutants of neuroligin-3 localized to excitatory postsynapses, while phospho-null mutants localized to inhibitory postsynapses. CONCLUSIONS: These data reveal an unexpected region-specific pattern of neuroligin-3 synapse specificity, as well as a phosphorylation-dependent mechanism that regulates its recruitment to either excitatory or inhibitory synapses. These findings add to our understanding of how neuroligin-3 is involved in conditions that may affect the balance of excitation and inhibition.

Mechanical and morphological characterisation of porcine urethras for the assessment of paediatric urinary catheter safety.

Paediatric urinary catheters are often necessary in critical care settings or to address congenital anomalies affecting the urogenital system. Iatrogenic injuries can occur during the placement of such catheters, highlighting the need for a safety device that can function in paediatric settings. Despite successful efforts to develop devices that improve the safety of adult urinary catheters, no such devices are available for use with paediatric catheters. This study investigates the potential for utilising a pressure-controlled safety mechanism to limit the trauma experienced by paediatric patients during inadvertent inflation of a urinary catheter anchoring balloon in the urethra. Firstly, we establish a paediatric model of the human urethra using porcine tissue by characterising the mechanical and morphological properties of porcine tissue at increasing postnatal timepoints (8, 12, 16 and 30 weeks). We identified that porcine urethras harvested from pigs at postnatal week 8 and 12 exhibit morphological properties (diameter and thickness) that are statistically distinct from adult porcine urethras (postnatal week 30). We therefore utilise urethra tissue from postnatal week 8 and 12 pigs as a model to evaluate a pressure-controlled approach to paediatric urinary catheter balloon inflation intended to limit tissue trauma during inadvertent inflation in the urethra. Our results show that limiting catheter system pressure to 150 kPa avoided trauma in all tissue samples. Conversely, all of the tissue samples that underwent traditional uncontrolled urinary catheter inflation experienced complete rupture. The findings of this study pave the way for the development of a safety device for use with paediatric catheters, thereby alleviating the burden of catastrophic trauma and life changing injuries in children due to a preventable iatrogenic urogenital event.

Identification of Nanoparticle Properties for Optimal Drug Delivery across a Physiological Cell Barrier.

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.

Comparison of macroscale and microscale mechanical properties of fresh and fixed-frozen porcine colonic tissue.

Mechanical changes to the microenvironment of the extracellular matrix (ECM) in tissue have been hypothesised to elicit a pathogenic response in the surrounding cells. Hence, 3D scaffolds are a popular method of studying cellular behaviour under conditions that mimic in vivo microenvironment. To create a 3D biomimetic scaffold that captures the in vivo ECM microenvironment a robust mechanical characterisation of the whole ECM at the microscale is necessary. This study examined the multiscale methods of characterising the ECM microenvironment using porcine colon tissue. To facilitate fresh tissue microscale mechanical characterisation, a protocol for sectioning fresh, unfixed, soft biological tissue was developed. Four experiments examined both the microscale and macroscale mechanics of both fresh (Fr) and fixed-frozen (FF) porcine colonic tissue using microindentation for microscale testing and uniaxial compression testing for macroscale testing. The results obtained in this study show a significant difference in elastic modulus between Fr and FF tissue at both the macroscale and microscale. There was an order of magnitude difference between the Fr and FF tissue at the microscale between each of the three layers of the colon tested i.e. the muscularis propria (MP), the submucosa (SM) and the mucosa (M). Macroscale testing cannot capture these regional differences. The findings in this study suggest that the most appropriate method for mechanically characterising the ECM is fresh microscale mechanical microindentation. These methods can be used on a range of biological tissues to create 3D biomimetic scaffolds that are more representative of the in vivo ECM, allowing for a more in-depth characterisation of the disease process.

The Role of Dietary Lipids in Cognitive Health: Implications for Neurodegenerative Disease.

Neurodegenerative diseases are a group of disorders characterised by progressive loss of brain function. The most common of these is Alzheimer's disease, a form of dementia. Intake of macro- and micro-nutrients impacts brain function, including memory, learning, mood, and behaviour. Lipids, particularly phospholipids and sphingolipids, are crucial structural components of neural tissues and significantly affect cognitive function. The importance of functional foods in preventing cardiovascular disease is well-documented in the current literature. However, the significance of such foods for central nervous system health and neurodegenerative diseases is less recognized. Gut microbiome composition affects cognitive health and function, and dietary lipids are known to influence gut health. Thus, this review will discuss different sources of dietary lipids and their effect on cognitive functioning and their interaction with the gut microbiome in the context of neurodegenerative disease.

A computational multilayer model to simulate hollow needle insertion into biological porcine liver tissue.

Modelling of needle insertion in soft tissue has developed significant interest in recent years due to its application in robot-assisted minimally invasive surgeries such as biopsies and brachytherapy. However, this type of surgery requires real-time feedback and processing which complex computational models may not be able to provide. In contrast to the existing mechanics-based kinetic models, a simple multilayer tissue model using a Coupled Eulerian Lagrangian based Finite Element method has been developed using the dynamic principle. The model simulates the needle motion for flexible hollow bevel-angled needle (15° and 30°, 22 Gauge) insertion into porcine liver tissue, which includes material parameters obtained from unconfined compression testing of porcine liver tissue. To validate simulation results, needle insertion force and cutting force within porcine liver tissue were compared with corresponding experimental results obtained from a custom-built needle insertion system. For the 15° and 30° bevel-angle needles, the percentage error for cutting force (mean) of each needle compared to computational model, were 18.7% and 11.9% respectively. Varying the needle bevel angle from 30° to 15° results in an increase of the cutting force, but insertion force does not vary among the tested bevel angles. The validation of this computationally efficient multilayer Finite Element model can help engineers to better understand the biomechanical behaviour of medical needle inside soft biological tissue. Ultimately, this multilayer approach can help advance state-of-art clinical applications such as robot-assisted surgery that requires real-time feedback and processing. STATEMENT OF SIGNIFICANCE: The significance of the work is in confirming the effectiveness of multilayer material based finite element (FE) method to model biopsy needle insertion into soft biological porcine liver tissue. A multilayer Coupled Eulerian Lagrangian (CEL) based FE modelling technique allowed testing of heterogeneous, non-linear viscoelastic porcine liver tissue in a system, so direct comparison of needle tissue interaction forces on the intrinsic material (tissue) behaviour could be made. To the best of the authors' knowledge, the present research investigates for the first time modelling of a three dimensional (3D) hollow needle insertion using a multilayer stiffness model of biological tissue using FE based CEL method and presents a comparison of simulation results with experimental data.

Vaginal Myomectomy and Total Vaginal Hysterectomy on Large Prolapsed Cervical Myoma: A Case Report.

Cervical myomas are benign tumors originating from cervical muscle tissue with a very rare incidence of only about 8% of all myomas. The surgical approach depends on the position of cervical myoma. This case report discusses a 44-year-old woman who complained of a lump discharge from her birth canal 6 months ago, and currently discharging from her vagina. We performed vaginal myomectomy, and the cervical myoma measuring 8 × 8 × 6 cm with solid consistency was removed. We continued with total vaginal hysterectomy. Post-operative recovery was progressing well. The histopathology report was consistent with leiomyoma. Large prolapsed cervical myoma can be disturbing and discomforting for many patients. It is relatively rare and can be successfully removed vaginally with minimal morbidity.

The effect of serum starvation on tight junctional proteins and barrier formation in Caco-2 cells.

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.

Mechanical characterisation of the human dura mater, falx cerebri and superior sagittal sinus.

The cranial meninges have been shown to play a pivotal role in traumatic brain injury mechanopathology. However, while the mechanical response of the brain and its many subregions have been studied extensively, the meninges have conventionally been overlooked. This paper presents the first comparative mechanical analysis of human dura mater, falx cerebri and superior sagittal sinus tissues. Biaxial tensile analysis identified that these tissues are mechanically heterogeneous, in contrast to the assumption that the tissues are mechanically homogeneous which is typically employed in FE model design. A thickness of 0.91 ± 0.05 (standard error) mm for the falx cerebri was also identified. This data can aid in improving the biofidelity of the influential falx structure in FE models. Additionally, the use of a collagen hybridizing peptide on the superior sagittal sinus suggests this structure is particularly susceptible to the effects of circumferential stretch, which may have important implications for clinical treatment of dural venous sinus pathologies. Collectively, this research progresses understanding of meningeal mechanical and structural characteristics and may aid in elucidating the behaviour of these tissues in healthy and diseased conditions. STATEMENT OF SIGNIFICANCE: This study presents the first evaluation of human falx cerebri and superior sagittal sinus mechanical, geometrical and structural properties, along with a comparison to cranial dura mater. To mechanically characterise the tissues, biaxial tensile testing is conducted on the tissues. This analysis identifies, for the first time, mechanical stiffness differences between these tissues. Additionally, geometrical analysis identifies that there are thickness differences between the tissues. The evaluation of human meningeal tissues allows for direct implementation of the novel data to finite element head injury models to enable improved biofidelity of these influential structures in traumatic brain injury simulations. This work also identifies that the superior sagittal sinus may be easily damaged during clinical angioplasty procedures, which may inform the treatment of dural sinus pathologies.

Cryopreservation of porcine urethral tissue: Storage at -20°C preserves the mechanical, failure and geometrical properties.

Cryopreservation is required to preserve the native properties of tissue for prolonged periods of time. In this study, we evaluate the impact that 4 different cryopreservation protocols have on porcine urethral tissue, to identify a protocol that best preserves the native properties of the tissue. The cryopreservation protocols include storage in cryoprotective agents at -20 °C and -80 °C with a slow, gradual, and fast reduction in temperature. To evaluate the effects of cryopreservation, the tissue is mechanically characterised in uniaxial tension and the mechanical properties, failure mechanics, and tissue dimensions are compared fresh and following cryopreservation. The mechanical response of the tissue is altered following cryopreservation, yet the elastic modulus from the high stress, linear region of the Cauchy stress - stretch curves is unaffected by the freezing process. To further investigate the change in mechanical response following cryopreservation, the stretch at different tensile stress values was evaluated, which revealed that storage at -20 °C is the only protocol that does not significantly alter the mechanical properties of the tissue compared to the fresh samples. Conversely, the ultimate tensile strength and the stretch at failure were relatively unaffected by the freezing process, regardless of the cryopreservation protocol. However, there were alterations to the tissue dimensions following cryopreservation that were significantly different from the fresh samples for the tissue stored at -80 °C. Therefore, any study intent on preserving the mechanical, failure, and geometric properties of urethral tissue during cryopreservation should do so by freezing samples at -20 °C, as storage at -80 °C is shown here to significantly alter the tissue properties.

On the association between circulating biomarkers and atherosclerotic calcification in a cohort of arterial disease participants.

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 (dp-ucMGP), 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 excised carotid specimens (rs = -0.366, P = 0.031). Despite substantial differences in coronary and extracoronary calcium measurements, the levels of circulating biomarkers did not vary significantly between carotid and lower extremity subgroups. CONCLUSION: Correlations identified between circulating biomarkers and measures of coronary and extracoronary calcium were not consistent among participant subgroups. Further research is required to determine the association between circulating biomarkers, coronary and extracoronary calcium.

Mechanical Properties of the Cranial Meninges: A Systematic Review.

The meninges are membranous tissues that are pivotal in maintaining homeostasis of the central nervous system. Despite the importance of the cranial meninges in nervous system physiology and in head injury mechanics, our knowledge of the tissues' mechanical behavior and structural composition is limited. This systematic review analyzes the existing literature on the mechanical properties of the meningeal tissues. Publications were identified from a search of Scopus, Academic Search Complete, and Web of Science and screened for eligibility according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review details the wide range of testing techniques employed to date and the significant variability in the observed experimental findings. Our findings identify many gaps in the current literature that can serve as a guide for future work for meningeal mechanics investigators. The review identifies no peer-reviewed mechanical data on the falx and tentorium tissues, both of which have been identified as key structures in influencing brain injury mechanics. A dearth of mechanical data for the pia-arachnoid complex also was identified (no experimental mechanics studies on the human pia-arachnoid complex were identified), which is desirable for biofidelic modeling of human head injuries. Finally, this review provides recommendations on how experiments can be conducted to allow for standardization of test methodologies, enabling simplified comparisons and conclusions on meningeal mechanics.

Mechanical and structural characterisation of the dural venous sinuses.

The dural venous sinuses play an integral role in draining venous blood from the cranial cavity. As a result of the sinuses anatomical location, they are of significant importance when evaluating the mechanopathology of traumatic brain injury (TBI). Despite the importance of the dural venous sinuses in normal neurophysiology, no mechanical analyses have been conducted on the tissues. In this study, we conduct mechanical and structural analysis on porcine dural venous sinus tissue to help elucidate the tissues' function in healthy and diseased conditions. With longitudinal elastic moduli values ranging from 33 to 58 MPa, we demonstrate that the sinuses exhibit higher mechanical stiffness than that of native dural tissue, which may be of interest to the field of TBI modelling. Furthermore, by employing histological staining and a colour deconvolution protocol, we show that the sinuses have a collagen-dominant extracellular matrix, with collagen area fractions ranging from 84 to 94%, which likely explains the tissue's large mechanical stiffness. In summary, we provide the first investigation of the dural venous sinus mechanical behaviour with accompanying structural analysis, which may aid in understanding TBI mechanopathology.

Bevel angle study of flexible hollow needle insertion into biological mimetic soft-gel: Simulation and experimental validation.

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°, 30°, 45°, 60° bevel angle needles, and 90° 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.

Comparing nanoparticles for drug delivery: The effect of physiological dispersion media on nanoparticle properties.

Delivering therapeutics to disease sites is a challenge facing modern medicine. Nanoparticle delivery systems are of considerable interest to overcome this challenge, but these systems suffer from poor clinical translation. It is believed this is, in part, due to incomplete understanding of nanoparticle physico-chemical properties in vivo. To understand how nanoparticle properties could change following intravenous delivery, Au, Ag, Fe2O3, TiO2, and ZnO nanoparticles of 5, 20, and 50 nm were characterised in water and physiological fluids. The effects of the dispersion medium, concentration, and incubation time on size, dispersion, and zeta potential were measured. Properties varied significantly depending on material type, size, and concentration over 24 h. Gold and silver nanoparticles were generally the most stable. Meanwhile, 20 nm nanoparticles appeared to be the least stable size, across materials. These results could have important implications for selecting nanoparticles for drug delivery that will elicit the desired physiological response.

Simulation of biopsy bevel-tipped needle insertion into soft-gel.

Planning and practice of surgical procedures can be improved through the use of modelling. This study provides an insight into the biopsy needle (i.e. hollow cannula) and needle-tissue interactions using a modelling approach, thus enabling the optimization of needle-tip designs not only for training but also for the planning of surgical procedures. Simulations of needle insertion into agar gel were performed using a Coupled Eulerian-Lagrangian (CEL) based finite element (FE) analysis, adapted for large deformation and tissue fracture. The experimental work covers needle insertion into 3% agar gel using a needle with a beveled tip of various angles, to assess the validity of the simulation. The simulated needle deflection and insertion force for two needles (i.e. Needle 1 with 18° bevel angle and Needle 2 with 27° bevel angle) were compared with corresponding experimental results. The contact stress (i.e. contact pressure) on the needles from the agar gel during the insertion of the needles were also studied. Observations indicate that varying the needle bevel angle from 27° to 18° results in a decrease of the peak force (i.e. puncture force) and an increase in needle deflection. Quantitatively, the percentage errors between the experimental data and the FE model for the total insertion force along the z-direction (i.e. Z Force) for Needle 1 and 2 were 4% and 4.8% (p > 0.05), respectively. Similarly, needle deflection percentage errors along the x-z plane were 5.7% and 10% respectively. Therefore, the forces and needle deflection values predicted by the simulation are a close approximation of the experimental model, validating the Coupled Eulerian-Lagrangian based FE model. Thus, providing an experimentally validated model for biopsy and cytology needle design in silico that has the potential to replace the current build and break approach of needle design used by manufacturers.

Standardization of research methods employed in assessing the interaction between metallic-based nanoparticles and the blood-brain barrier: Present and future perspectives.

Treating diseases of the central nervous system (CNS) is complicated by the presence of the blood-brain barrier (BBB), a semipermeable boundary layer protecting the CNS from toxins and homeostatic disruptions. However, this layer also excludes almost 100% of therapeutics, impeding the treatment of CNS diseases. The advent of nanoparticles, in particular metallic-based nanoparticles, presents the potential to overcome this barrier and transport drugs into the CNS. Recent interest in metallic-based nanoparticles has generated an immense array of information pertaining to nanoparticles of different materials, sizes, morphologies, and surface properties. Nanoparticles with different physico-chemical properties lead to distinct nanoparticle-host interactions; yet, comprehensive characterization is often not completed. Similarly, in vivo testing has involved a mixed evaluation of parameters, including: BBB permeability, integrity, biodistribution, and toxicity. The methods applied to assess these parameters are inconsistent; this complicates the comparison of different nanoparticle-host system responses. A systematic review was conducted to investigate the methods by which metallic-based nanoparticles are characterized and assessed in vivo. The introduction of a standardized approach to nanoparticle characterization and in vivo testing is crucial if research is to transition to a clinical setting. The approach suggested, herein, is based on equipment and techniques that are accessible and informative to facilitate the routine incorporation of this standardized, informative approach into different research settings. Thorough characterization could lead to improved interpretation of in vivo responses, which could clarify nanoparticle properties that result in favorable in vivo outcomes whilst exposing nanoparticle-specific weaknesses. Only then will researchers successfully identify nanoparticles capable of delivering life-saving therapeutics across the blood-brain barrier.

Digital and Mechanical Characterization of Ureteral Stent Luminal Reduction in Response to Extrinsic Compression Forces.

PURPOSE: To investigate the principles that govern ureteral stent failure by digitally and mechanically characterizing their luminal reduction in response to various extrinsic compression forces. To explore the relationship between ureteral stent "material area," "luminal area," and "cross-sectional area (CSA)" for resisting extrinsic compression forces. MATERIALS AND METHODS: We mechanically investigated 4.8F (n = 9), 6F (n = 9), and 7F (n = 9) ureteral stents to determine parameters that contribute to resisting radial compression forces. Digitalized images of luminal reduction values under incrementally increased reductions of stent outer diameters were obtained (0%, 25%, 50%, and 60% of original outer diameter). Forces (Newton [N]) and percentage luminal reduction that resulted in complete ureteral stent obstruction were determined. RESULTS: Uniaxial incremental compression in the radial direction demonstrated complete luminal reduction (95%-100%) when 58% to 62% of the outer stent diameter was compressed. The 6F ureteral stents demonstrated the greatest resistance to extrinsic compression and the greatest "material area" relative to "CSA" (mm2). The force (N) required for 50% compression of outer stent diameter was 10.44, 28.13, and 25.39 N for 4.8F, 6F, and 7F ureteral stents, respectively. The "material area"/"CSA" at 50% compression of the outer stent diameter was 76%, 86%, and 78% for 4.8F, 6F, and 7F ureteral stents, respectively. CONCLUSIONS: Maintenance of intraluminal stent diameter in the presence of extrinsic compressive forces is primarily dependent on the stent's ratio of "material area" to "CSA." Urologists should be aware of these findings to decrease the risk of ureteral stent failure when treating extrinsic ureteral obstruction.