A comprehensive simulation framework for predicting the eCLIPs implant crimping into a catheter and its deployment mechanisms.

Tubular flow diverters (FDs) represent an important subset of the endovascular treatment of cerebral aneurysms (CAs), acting to reduce aneurysm inflow, eventually resulting in aneurysm thrombosis and occlusion. eCLIPs (product of Evasc Neurovascular Enterprises, Vancouver, Canada), an innovative non-tubular implant causes flow diversion by bridging the neck of bifurcation CAs. However, in a small subset of challenging bifurcation aneurysms with fusiform pathology, the currently available eCLIPs models do not provide sufficient neck bridging resulting in a gap created between the device structure and the aneurysm/artery wall. To overcome this challenge, a new design of the eCLIPs (VR-eCLIPs) was developed by varying the rib length to cover such an inflow gap. To optimize the new product development process, and avoiding expensive and time-consuming iterative manufacture of prototype devices, we have developed a new finite element model to simulate the crimping and expansion processes of the VR-eCLIPs implant, and assess the possibility of plastic deformation. Results indicated that neither eCLIPs nor VR-eCLIPs experience plastic deformation during the crimping process. Upon full expansion, the ribs of VR-eCLIPs interact with the aneurysm and artery wall to cover the inflow gap that exists in certain challenging anatomies. This process serves as a basis to expedite design development prior to prototype manufacturing.

Yield stress analysis of cellulose nanocrystals (CNCs) in hyaluronic acid suspensions.

Due to their biodegradability features, cellulose nanocrystals (CNCs) and hyaluronic acid (HA) have been simultaneously used in the matrix of hydrogels for biomedical applications, such as corneal transplantation, and skin regeneration. Although rheology of these hydrogels may provide useful information for their applications, little to no attention has been paid to rheological characterization. In this study, we analyzed the rheology of HA-CNC suspensions and more specifically their yielding behavior. Through different rheological experiments, known as stress ramp, shear rate ramp and amplitude sweep; it was observed that HA-CNC gels possessed two yield points. Reproducible magnitudes of yield stress were obtained by optimizing the experimental conditions. The rheo-optics characterizations confirmed that the first and second yield points could be attributed to the bond and cage breakage phenomena. Studying the effect of concentration, the second yield stress increased linearly by CNC concentration, whereas the first yield point manifested a power-law dependence on concentration (exponent of 0.5). This power-law relationship was further justified by the evolution of average distance between the CNC individual particles (d), calculated through SAXS analysis.

Robust Nanoparticle-Derived Lubricious Antibiofilm Coating for Difficult-to-Coat Medical Devices with Intricate Geometry.

A major medical device-associated complication is the biofilm-related infection post-implantation. One promising approach to prevent this is to coat already commercialized medical devices with effective antibiofilm materials. However, developing a robust high-performance antibiofilm coating on devices with a nonflat geometry remains unmet. Here, we report the development of a facile scalable nanoparticle-based antibiofilm silver composite coating with long-term activity applicable to virtually any objects including difficult-to-coat commercially available medical devices utilizing a catecholic organic-aqueous mixture. Using a screening approach, we have identified a combination of the organic-aqueous buffer mixture which alters polycatecholamine synthesis, nanoparticle formation, and stabilization, resulting in controlled deposition of in situ formed composite silver nanoparticles in the presence of an ultra-high-molecular-weight hydrophilic polymer on diverse objects irrespective of its geometry and chemistry. Methanol-mediated synthesis of polymer-silver composite nanoparticles resulted in a biocompatible lubricious coating with high mechanical durability, long-term silver release (∼90 days), complete inhibition of bacterial adhesion, and excellent killing activity against a diverse range of bacteria over the long term. Coated catheters retained their excellent activity even after exposure to harsh mechanical challenges (rubbing, twisting, and stretching) and storage conditions (>3 months stirring in water). We confirmed its excellent bacteria-killing efficacy (>99.999%) against difficult-to-kill bacteria (Proteus mirabilis) and high biocompatibility using percutaneous catheter infection mice and subcutaneous implant rat models, respectively, in vivo. The developed coating approach opens a new avenue to transform clinically used medical devices (e.g., urinary catheters) to highly infection-resistant devices to prevent and treat implant/device-associated infections.

Durable Surfaces from Film-Forming Silver Assemblies for Long-Term Zero Bacterial Adhesion without Toxicity.

The long-term prevention of biofilm formation on the surface of indwelling medical devices remains a challenge. Silver has been reutilized in recent years for combating biofilm formation due to its indisputable bactericidal potency; however, the toxicity, low stability, and short-term activity of the current silver coatings have limited their use. Here, we report the development of silver-based film-forming antibacterial engineered (SAFE) assemblies for the generation of durable lubricous antibiofilm surface long-term activity without silver toxicity that was applicable to diverse materials via a highly scalable dip/spray/solution-skinning process. The SAFE coating was obtained through a large-scale screening, resulting in effective incorporation of silver nanoparticles (∼10 nm) into a stable nonsticky coating with high surface hierarchy and coverage, which guaranteed sustained silver release. The lead coating showed zero bacterial adhesion over a 1 month experiment in the presence of a high load of diverse bacteria, including difficult-to-kill and stone-forming strains. The SAFE coating showed high biocompatibility and excellent antibiofilm activity in vivo.

Effect of ultrasonic treatment on yield stress of highly concentrated cellulose nano-crystalline (CNC) aqueous suspensions.

The yield stress of highly concentrated cellulose nano-crystalline (CNC) suspensions is an important rheological property for different applications. The ultrasonic treatment is a common technique for dispersing CNCs in aqueous media. Although the effect of ultrasonic processing on rheology of CNC suspensions has been previously investigated, a systematic approach studying the sonication effect on yield stress is missing in the literature. In this study, we investigated the effect of sonication energy within the energy level of 0-5000 J/gCNC on static, dynamic and true yield points of a highly concentrated (8 wt%) aqueous CNC suspension, through a rheo-optics analysis. To better understand the yielding behaviour, the sonication effect on physicochemical properties of the CNCs was also investigated. The results revealed that yield stress decreases with sonication energy through a four-step mechanism governed by the microstructural transformations of the CNC agglomerates.

Percutaneous delivery of self-propelling thrombin-containing powder increases survival from noncompressible truncal hemorrhage in a swine model of coagulopathy and hypothermia.

BACKGROUND: Noncompressible truncal hemorrhage (NCTH) remains a leading cause of preventable death on the battlefield. Definitively managing severe NCTH requires surgery within the first hour after injury, which is difficult when evacuating casualties from remote and austere environments. During delays to surgery, hemostatic interventions that are performed prehospital can prevent coagulopathy and hemorrhagic shock and increase the likelihood that casualties survive to receive definitive care. We previously reported that a self-propelling thrombin-containing powder (SPTP) can be delivered percutaneously into the abdomen as a minimally invasive intervention and can self-disperse through pooled blood to deliver the hemostatic agents thrombin and tranexamic acid locally to noncompressible intracavitary wounds. We hypothesized that, in swine with massive NCTH, dilutional coagulopathy, and hypothermia, delivering SPTP could extend survival times. METHODS: Ten swine (n = 5 per group) underwent NCTH from a Grade V liver injury following a midline laparotomy. The laparotomy was closed with sutures afterwards, creating a hemoperitoneum, and animals were managed with crystalloid fluid resuscitation, or crystalloid resuscitation and SPTP. Self-propelling thrombin-containing powder was delivered into the closed abdomen using a CO 2 -powered spray device and a catheter placed into the hemoperitoneum, entering through the upper right quadrant using the Seldinger technique. Survival to 1 and 3 hours was recorded. In an additional animal, hemorrhage was created laparoscopically, and SPTP was imaged in situ within the abdomen to visually track dispersion of the particles. RESULTS: Self-propelling thrombin-containing powder dispersed as far as 35 ± 5.0 cm within the abdomen. It increased survival to 1 and 3 hours (Kaplan-Meier p = 0.007 for both). The median survival time was 61 minutes with SPTP and 31 minutes without ( p = 0.016). CONCLUSION: Self-propelling thrombin-containing powder effectively disperses medications throughout a hemoperitoneum and increases survival in a model of NCTH. It is a promising strategy for nonsurgical management of NCTH, warranting further testing of its safety and efficacy.

Effect of ultrasonication on lubrication performance of cellulose nano-crystalline (CNC) suspensions as green lubricants.

Industrial lubricants are widely introduced to the mechanical systems to reduce the wear and energy losses. With the increasing demand for environmental protection, developing eco-friendly lubricants becomes more crucial. Due to their abundance, biodegradability, non-toxicity, high thermal stability and low cost, cellulose nanocrystals (CNCs) may be an appropriate choice for formulating green lubricants. In this study, using different microstructural and tribological characterization methods, we systematically investigated the effect of ultrasonic treatment on lubrication performance of CNC aqueous suspensions. It was observed that within sonication energy of 4-50 kJ/gCNC, there exists an optimum condition for tribological measurements. In comparison to the unsonicated suspensions, sonicated CNC lubricants could decrease COF (coefficient of friction) and wear by almost 25 and 30% respectively. Results of this study suggest that ultrasonication processing can significantly improve lubrication performance of CNC aqueous suspensions.

Rheological and clot microstructure evaluation of heparin neutralization by UHRA and protamine.

The current study reports the use of small amplitude oscillatory rheometry to investigate the dynamics of blood clot formation upon heparin neutralization under three different oscillatory frequencies, two of which were mimicking physiological heart rates. We utilized two different heparin antidotes, namely protamine and newly developed universal heparin reversal agent (UHRA-7), at different concentrations to determine the quality of blood clot formed upon heparin neutralization by analyzing several key rheological parameters. Scanning electron microscopy (SEM) was used to determine the morphology and microstructure of the blood clot after heparin neutralization to support the rheological observations. The current study revealed that the structure of blood clots formed had significant differences when an oscillatory frequency that mimicked the physiological heart rate was used in comparison to a lower frequency commonly used in current clinical measurements. The limited working dose range for protamine and its intrinsic anticoagulation behaviour was observed. The neutralization profile of UHRA-7 showed a large window of activity. The global assessment of rheological parameters and microstructure of the clot together revealed additional details describing anticoagulant reversal and blood coagulation dynamics by relating the blood clot's fiber thickness and the oscillatory measurements, including storage modulus and blood clot's contractile force. Additionally, a mechanical characterization was conducted to provide a further assessment of blood coagulation using the rheological data.

Self-Limiting Mussel Inspired Thin Antifouling Coating with Broad-Spectrum Resistance to Biofilm Formation to Prevent Catheter-Associated Infection in Mouse and Porcine Models.

Catheter-associated urinary tract infections (CAUTIs) are one of the most commonly occurring hospital-acquired infections. Current coating strategies to prevent catheter-associated biofilm formation are limited by their poor long-term efficiency and limited applicability to diverse materials. Here, the authors report a highly effective non-fouling coating with long-term biofilm prevention activity and is applicable to diverse catheters. The thin coating is lubricous, stable, highly uniform, and shows broad spectrum prevention of biofilm formation of nine different bacterial strains and prevents the migration of bacteria on catheter surface. The coating method is adapted to human-sized catheters (both intraluminal and extraluminal) and demonstrates long-term biofilm prevention activity over 30 days in challenging conditions. The coated catheters are tested in a mouse CAUTI model and demonstrate high efficiency in preventing bacterial colonization of both Gram-positive and Gram-negative bacteria. Furthermore, the coated human-sized Foley catheters are evaluated in a porcine CAUTI model and show consistent efficiency in reducing biofilm formation by Escherichia coli (E. coli) over 95%. The simplicity of the coating method, the ability to apply this coating on diverse materials, and the high efficiency in preventing bacterial adhesion increase the potential of this method for the development of next generation infection resistant medical devices.

The influence of hematocrit on the hemodynamics of artificial heart valve using fluid-structure interaction analysis.

Patients with severe aortic stenosis could regain the proper hemodynamic performance and cardiovascular output by restoring the diseased aortic valve with an artificial heart valve replacement. However, given the uniqueness of each patient, the hemodynamic improvements after an aortic valve replacement could vary. The biomechanical and hemodynamical parameters can be influenced by some major factors including the patient's blood pressure and hematocrit. Therefore, the objective of this study is to analyze the hemodynamics and valve mechanics of a bileaflet mechanical heart valve and investigate the hemorheological characteristics under the change of hematocrit. The fully coupled fluid-structure interaction (FSI) approach was used to model the hemodynamics and valve dynamics. Particle image velocimetry (PIV) experiments were conducted with in vitro benchtop model using ViVitro Pulse Duplicator to verify and validate the FSI models. The current numerical analysis revealed the hematocrit influenced the shear stress distributions over a cardiac cycle. The structural stresses in the mechanical valve were also affected by the distributions of the shear stress in the blood flow. Parameter dependencies found in the current study indicate that the hematocrit is influential when conducting patient-specific modelling of prosthetic heart valves.

Influence of dynamic flow conditions on adsorbed plasma protein corona and surface-induced thrombus generation on antifouling brushes.

The information regarding the nature of protein corona (and its changes) and cell binding on biomaterial surface under dynamic conditions is critical to dissect the mechanism of surface-induced thrombosis. In this manuscript, we investigated the nature of protein corona and blood cell binding in heparinized recalcified human plasma, platelet rich plasma and whole blood on three highly hydrophilic antifouling polymer brushes, (poly(N, N-dimethylacrylamide) (PDMA), poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) using an in vitro blood loop model at comparable arterial and venous flow, and static conditions. A fluid dynamics model was used initially to better understand the resulting flow patterns in a vertical channel containing the substrates to arrive at the placement of the substrates within the blood loop. The protein binding on the brush modified substrates was determined using ellipsometry, fluorescence microscopy and the nature of the protein corona was investigated using mass spectrometry based proteomics. The flow elevated fouling on brush coated surface from blood. The extent of plasma protein adsorption and platelet adhesion onto PDMA brush was lower than other surfaces in both static and flow conditions. The profiles of adsorbed protein corona showed strong dependence on the test conditions (static vs. flow), and the chemistry of the polymer brushes. Specially, the PDMA brush under flow conditions was more enriched with coagulation proteins, complement proteins, vitronectin and fibronectin but was less enriched with serum albumin. Apolipoprotein B-100 and complement proteins were the most abundant proteins seen on PMPC and PHPMA surfaces under both flow and static conditions, respectively. Unlike PDMA brush, the flow conditions did not affect the composition of protein corona on PMPC and PHPMA brushes. The nature of the protein corona formed in flow conditions influenced the platelet and red blood cell binding. The dependence of shear stress on platelet adhesion from platelet rich plasma and whole blood highlights the contribution of red blood cells in enhancing platelet adhesion on the surface under high shear condition.

Hemodynamic assessments of the ascending thoracic aortic aneurysm using fluid-structure interaction approach.

Current assessment and management of ascending thoracic aortic aneurysm (ATAA) rely heavily on the diameter of the ATAA and blood pressure rather than biomechanical and hemodynamic parameters such as arterial wall deformation or wall shear stress. The objective of the current study was to develop an accurate computational method for modeling the mechanical responses of the ATAA to provide additional information in patient evaluations. Fully coupled fluid structure interaction simulations were conducted using data from cases with ATAA with measured geometrical parameters in order to evaluate and analyze the change in biomechanical responses under normotensive and hypertensive conditions. Anisotropic hyperelastic material property estimates were applied to the ATAA data which represented three different geometrical configurations of ATAAs. The resulting analysis showed significant variations in maximum wall shear stress despite minimal differences in flow velocity between two blood pressure conditions. Additionally, the three different ATAA conditions identified different aortic expansions that were not uniform under pulsatile pressure. The elevated wall stress with hypertension was also geometry-dependent. The developed models suggest that ATTA cases have unique characteristic in biomechanical and hemodynamic evaluations that can be useful in risk management.

Rheological study of hyaluronic acid derivatives.

The viscoelastic properties of four novel, low molecular weight hyaluronic acid derivatives were investigated and compared to the parent hyaluronic acid compound. Briefly, all derivatives were synthesized by first deacetylating the parent hyaluronic acid. One sample was left as such, while two others were reacytelated. The final compound, of particular interest for its anti-inflammatory properties, was butyrylated. The compounds were dissolved in phosphate buffer solution (PBS) and studied at a concentration of 5 mg/mL. Shear thinning behaviour was observed for all compounds, however, derivative samples had a lower viscosity than the parent compound at high shear rates. Viscoelastic properties were also observed to decrease as a result of the derivative preparation method. It is believed that these changes are primarily caused by a decrease in hyaluronic acid molecular weight. By increasing the concentration of the anti-inflammatory compound, it may be possible to modulate the viscoelastic properties to more closely resemble those of commercial viscosupplements. As a result, an anti-inflammatory derivative of hyaluronic acid may potentially improve upon existing viscosupplements used to treat patients who are susceptible to flare up.

Osteoarthritic synovial fluid rheology and correlations with protein concentration.

BACKGROUND: Osteoarthritis is a common, localized joint disease that causes pain, stiffness and reduced mobility. Osteoarthritis is particularly common in the knees. The effects of osteoarthritis on the rheology of synovial fluid in the knees are not fully understood and consequently require further study. OBJECTIVE: The purpose of this study is to investigate the effects of protein content on synovial fluid shear rheology. A secondary study outcome will include study of the temperature dependence of synovial fluid behaviour. METHODS: 38 osteoarthritic synovial fluid samples were studied under shear flow. Shear properties were correlated with protein concentration. Viscosupplement was used as a comparison and to verify measurement reliability. The effects of temperature were investigated at 20, 29 and 37°C. RESULTS: Shear rheological properties were found to vary widely between samples, however all samples demonstrated clear non-Newtonian shear thinning behaviour. In general viscoelastic properties were lower in osteoarthritic samples than previously studied healthy synovial fluid. A moderate correlation was observed between synovial fluid dynamic moduli at a frequency of 2.5 Hz and protein concentration. Temperature was found to affect the rheology of osteoarthritic synovial fluid and was fitted with the Arrhenius model. CONCLUSIONS: Increased protein concentration has been correlated with decreased shear rheological parameters. Temperature dependence of synovial fluid was also demonstrated and modelled for use in Part 2 of this article.

Osteoarthritic synovial fluid and correlations with protein concentration.

BACKGROUND: Osteoarthritis is a common, localized joint disease that causes pain, stiffness and reduced mobility. The effects of osteoarthritis on the extensional rheology of synovial fluid in the knees are not fully understood and consequently require further study. OBJECTIVE: The purpose of this work is to study the extensional rheology of osteoarthritic synovial fluid and to investigate a possible correlation between synovial fluid protein concentration and extensional rheology. The study will also investigate possible correlations with the shear rheology. METHODS: 21 osteoarthritic synovial fluid samples were studied under extensional flow with a capillary breakup extensional rheometer. Extensional rheological properties were correlated with protein concentration and with shear rheological properties measured in a prior study. Viscosupplement was also studied under extensional flow for comparison. RESULTS: Extensional rheological properties were found to vary widely between samples, but in general were found to agree with previous studies. No statistically significant correlation was identified between extensional rheological properties and protein concentration. Positive correlations were identified between zero shear viscosity and terminal extensional viscosity (R-squared = 0.73), zero shear viscosity and extensional relaxation time (R-squared = 0.84), and shear relaxation time and extensional relaxation time (R-squared = 0.75). CONCLUSIONS: Appropriate CaBER operating parameters for study of osteoarthritic synovial fluid were identified. No statistically significant correlation was found to exist between protein concentration and extensional rheological parameters. Positive correlations were identified between several shear and extensional rheological parameters. The reported values for extensional viscosity and relaxation times for synovial fluid were found to be within one order of magnitude with a recent study of post mortem synovial fluid.

Shear-induced textural transitions in flow-aligning liquid crystal polymers.

The equations of nematodynamics are formulated, solved, and used to model textural transformations in sheared thermotropic flow-aligning nematic polymers. The solutions are classified and characterized using analytical, scaling, and numerical methods. It is found that as the shear rate increases, the pathway between an oriented nonplanar state and an oriented planar state is through texture formation and coarsening. The two shear-rate dependent dimensionless numbers that control the texture formation and coarsening process are Ericksen Er and Deborah De numbers. The emergence of texture is independent of the Deborah number, and occurs at Er=10(4). As the shear rate increases and Er>10(4) the first texture that arises is a defect lattice. Further increases of the shear rate bring De close to 1, ignite the coarsening processes, and replace the defect lattice with a defect gas. The smallest texture length scale l(t) occurs at the defect lattice-defect gas transition. In the defect lattice regime the texture length scale decreases with increasing shear rate as l(t) proportional to (gamma-a)(-1/2), while in the defect gas regime it increases as l(t) proportional to (gamma-b sqrt[(gamma-a)]-c)(-1). Finally when De>2, an oriented monodomain state emerges, and the texture vanishes since coarsening overpowers defect nucleation. It is found that the texture transition cascade unoriented monodomain=>defect lattice=>defect gas=>oriented monodomain is remarkably consistent with the experimentally observed textural transitions of sheared lyotropic nematic polymers.