Mechanical and leakage integrity testing considerations for evaluating the performance of tissue containment systems.

Tissue containment systems (TCS) are medical devices that may be used during morcellation procedures during minimally invasive laparoscopic surgery. TCS are not new devices but their use as a potential mitigation for the spread of occult malignancy during laparoscopic power morcellation of fibroids and/or the uterus has been the subject of interest following reports of upstaging of previously undetected sarcoma in women who underwent a laparoscopic hysterectomy. Development of standardized test methods and acceptance criteria to evaluate the safety and performance of these devices will speed development, allowing for more devices to benefit patients. As a part of this study, a series of preclinical experimental bench test methods were developed to evaluate the mechanical and leakage performance of TCS that may be used in power morcellation procedures. Experimental tests were developed to evaluate mechanical integrity, e.g., tensile, burst, puncture, and penetration strengths for the TCS, and leakage integrity, e.g., dye and microbiological leakage (both acting as surrogates for blood and cancer cells) through the TCS. In addition, to evaluate both mechanical integrity and leakage integrity as a combined methodology, partial puncture and dye leakage was conducted on the TCS to evaluate the potential for leakage due to partial damage caused by surgical tools. Samples from 7 different TCSs were subjected to preclinical bench testing to evaluate leakage and mechanical performance. The performance of the TCSs varied significantly between different brands. The leakage pressure of the TCS varied between 26 and > 1293 mmHg for the 7 TCS brands. Similarly, the tensile force to failure, burst pressure, and puncture force varied between 14 and 80 MPa, 2 and 78 psi, and 2.5 N and 47 N, respectively. The mechanical failure and leakage performance of the TCS were different for homogeneous and composite TCSs. The test methods reported in this study may facilitate the development and regulatory review of these devices, may help compare TCS performance between devices, and increase provider and patient accessibility to improved tissue containment technologies.

Fluid-Structure Interaction Models of Bioprosthetic Heart Valve Dynamics in an Experimental Pulse Duplicator.

Computer modeling and simulation is a powerful tool for assessing the performance of medical devices such as bioprosthetic heart valves (BHVs) that promises to accelerate device design and regulation. This study describes work to develop dynamic computer models of BHVs in the aortic test section of an experimental pulse-duplicator platform that is used in academia, industry, and regulatory agencies to assess BHV performance. These computational models are based on a hyperelastic finite element extension of the immersed boundary method for fluid-structure interaction (FSI). We focus on porcine tissue and bovine pericardial BHVs, which are commonly used in surgical valve replacement. We compare our numerical simulations to experimental data from two similar pulse duplicators, including a commercial ViVitro system and a custom platform related to the ViVitro pulse duplicator. Excellent agreement is demonstrated between the computational and experimental results for bulk flow rates, pressures, valve open areas, and the timing of valve opening and closure in conditions commonly used to assess BHV performance. In addition, reasonable agreement is demonstrated for quantitative measures of leaflet kinematics under these same conditions. This work represents a step towards the experimental validation of this FSI modeling platform for evaluating BHVs.

A Computational Study on Deformed Bioprosthetic Valve Geometries: Clinically Relevant Valve Performance Metrics.

Transcatheter aortic valves (TAV) are symmetrically designed, but they are often not deployed inside cylindrical conduits with circular cross-sectional areas. Many TAV patients have heavily calcified aortic valves, which often result in deformed prosthesis geometries after deployment. We investigated the effects of deformed valve annulus configurations on a surgical bioprosthetic valve as a model for TAV. We studied valve leaflet motions, stresses and strains, and analog hydrodynamic measures (using geometric methods), via finite element (FE) modeling. Two categories of annular deformations were created to approximate clinical observations: (1) noncircular annulus with valve area conserved, and (2) under-expansion (reduced area) compared to circular annulus. We found that under-expansion had more impact on increasing stenosis (with geometric orifice area metrics) than noncircularity, and that noncircularity had more impact on increasing regurgitation (with regurgitation orifice area metrics) than under-expansion. We found durability predictors (stress/strain) to be the highest in the commissure regions of noncircular configurations such as EllipMajor (noncircular and under-expansion areas). Other clinically relevant performance aspects such as leaflet kinematics and coaptation were also investigated with the noncircular configurations. This study provides a framework for choosing the most challenging TAV deformations for acute and long-term valve performance in the design and testing phase of device development.

In Vitro Leakage Testing of Tissue Containment Bags When Subjected to Power Morcellation Forces.

STUDY OBJECTIVE: To determine the ability of tissue containment systems to prevent leakage of cancer cell surrogates when subjected to forces encountered during power morcellation procedures. DESIGN: In vitro study. SETTING: Medical device research laboratory. INTERVENTIONS: Samples from 7 different legally marketed tissue containment bags (1 of which is indicated for power morcellation) were subjected to dye and bacteriophage penetration tests at pressures ranging from 0.5 to 50 times the insufflation pressure. The minimum pressure required to cause bag leakage was measured. Subsequently, the morcellation leakage safety factor for each bag was determined as the ratio of the minimum leakage pressure of the bag to the total pressure contributed from insufflation pressure and mechanical forces acting during the power morcellation procedure. MEASUREMENT AND MAIN RESULTS: The leakage performance of the bags varied markedly from brand to brand. No correlation was found between leakage pressure and the bag material or the total bag thickness. The leakage pressures ranged from 26 mmHg to >1293 mmHg for the 7 bags, and safety factors ranged from 1 to 50 when only the insufflation pressure was considered. However, if the morcellation forces were included in the calculation, the safety factor dropped by 6-fold for all brands and dropped below 1, indicating likelihood of leakage, for 2 of the 7 brands. CONCLUSION: This study provides a mechanism for more realistically simulating the conditions experienced by containment bags during morcellation and quantifying the level of safety provided by the bags.

Impact of Clinically Relevant Elliptical Deformations on the Damage Patterns of Sagging and Stretched Leaflets in a Bioprosthetic Heart Valve.

After implantation of a transcatheter bioprosthetic heart valve its original circular circumference may become distorted, which can lead to changes in leaflet coaptation and leaflets that are stretched or sagging. This may lead to early structural deterioration of the valve as seen in some explanted transcatheter heart valves. Our in vitro study evaluates the effect of leaflet deformations seen in elliptical configurations on the damage patterns of the leaflets, with circular valve deformation as the control. Bovine pericardial tissue heart valves were subjected to accelerated wear testing under both circular (N = 2) and elliptical (N = 4) configurations. The elliptical configurations were created by placing the valve inside custom-made elliptical holders, which caused the leaflets to sag or stretch. The hydrodynamic performance of the valves was monitored and high resolution images were acquired to evaluate leaflet damage patterns over time. In the elliptically deformed valves, sagging leaflets experienced more damage from wear compared to stretched leaflets; the undistorted leaflets of the circular valves experienced the least leaflet damage. Free-edge thinning and tearing were the primary modes of damage in the sagging leaflets. Belly region thinning was seen in the undistorted and stretched leaflets. Leaflet and fabric tears at the commissures were seen in all valve configurations. Free-edge tearing and commissure tears were the leading cause of valve hydrodynamic incompetence. Our study shows that mechanical wear affects heart valve pericardial leaflets differently based on whether they are undistorted, stretched, or sagging in a valve configuration. Sagging leaflets are more likely to be subjected to free-edge tear than stretched or undistorted leaflets. Reducing leaflet stress at the free edge of non-circular valve configurations should be an important factor to consider in the design and/or deployment of transcatheter bioprosthetic heart valves to improve their long-term performance.

A Parametric Computational Study of the Impact of Non-circular Configurations on Bioprosthetic Heart Valve Leaflet Deformations and Stresses: Possible Implications for Transcatheter Heart Valves.

Although generally manufactured as circular devices with symmetric leaflets, transcatheter heart valves can become non-circular post-implantation, the impact of which on the long-term durability of the device is unclear. We investigated the effects of five non-circular (EllipMajor, EllipMinor, D-Shape, TriVertex, TriSides) annular configurations on valve leaflet stresses and valve leaflet deformations through finite element analysis. The highest in-plane principal stresses and strains were observed under an elliptical configuration with an aspect ratio of 1.25 where one of the commissures was on the minor axis of the ellipse. In this elliptical configuration (EllipMinor), the maximum principal stress increased 218% and the maximum principal strain increased 80% as compared with those in the circular configuration, and occurred along the free edge of the leaflet whose commissures were not on the minor axis (i.e., the "stretched" leaflet). The D-Shape configuration was similar to this elliptical configuration, with the degree to which the leaflets were stretched or sagging being less than the EllipMinor configuration. The TriVertex and TriSides configurations had similar leaflet deformation patterns in all three leaflets and similar to the Circular configuration. In the D-Shape, TriVertex, and TriSides configurations, the maximum principal stress was located near the commissures similar to the Circular configuration. In the EllipMinor and EllipMajor configurations, the maximum principal stress occurred near the center of the free edge of the "stretched" leaflets. These results further affirm recommendations by the International Standards Organization (ISO) that pre-clinical testing should consider non-circular configurations for transcatheter valve durability testing.

Comparison of near-wall hemodynamic parameters in stented artery models.

Four commercially available stent designs (two balloon expandable-Bx Velocity and NIR, and two self-expanding-Wallstent and Aurora) were modeled to compare the near-wall flow characteristics of stented arteries using computational fluid dynamics simulations under pulsatile flow conditions. A flat rectangular stented vessel model was constructed and simulations were carried out using rigid walls and sinusoidal velocity input (nominal wall shear stress of 10+/-5 dyn/cm2). Mesh independence was determined from convergence (<10%) of the axial wall shear stress (WSS) along the length of the stented model. The flow disturbance was characterized and quantified by the distributions of axial and transverse WSS, WSS gradients, and flow separation parameters. Normalized time-averaged effective WSS during the flow cycle was the smallest for the Wallstent (2.9 dyn/cm2) compared with the others (5.8 dyn/cm2 for the Bx Velocity stent, 5.0 dyn/cm2 for the Aurora stent, and 5.3 dyn/cm2 for the NIR stent). Regions of low mean WSS (<5 dyn/cm2) and elevated WSS gradients (>20 dyn/cm3) were also the largest for the Wallstent compared with the others. WSS gradients were the largest near the struts and remained distinctly nonzero for most of the region between the struts for all stent designs. Fully recirculating regions (as determined by separation parameter) were the largest for the Bx Velocity stent compared with the others. The most hemodynamically favorable stents from our computational analysis were the Bx Velocity and NIR stents, which were slotted-tube balloon-expandable designs. Since clinical data indicate lower restenosis rates for the Bx Velocity and NIR stents compared with the Wallstent, our data suggest that near-wall hemodynamics may predict some aspects of in vivo performance. Further consideration of biomechanics, including solid mechanics, in stent design is warranted.

A phospholipid-modified polystyrene-polyisobutylene-polystyrene (SIBS) triblock polymer for enhanced hemocompatibility and potential use in artificial heart valves.

Poly(styrene-block-isobutylene-block-styrene) ('SIBS') is selected for a novel tri-leaflet heart valve due to its high resistance to oxidation, hydrolysis, and enzyme attack. SIBS is modified using six different phospholipids and its mechanical properties characterized by tensile stress, peel strength, shear strength, contact angle, and surface energy, and then for hemocompatibility by studying the adhesion of fluorescently labeled platelets in a parallel plate chamber under physiological flow conditions. Phospholipid modification decreases SIBS tensile stress (at 45% strain) by 30% and reduces platelet adhesion by a factor of 10, thereby improving its hemocompatibility and its potential use as a synthetic heart valve.

Effects of stent geometry on local flow dynamics and resulting platelet deposition in an in vitro model.

Platelet deposition has been shown previously to depend on convective transport patterns, visualized by the instantaneous streamlines. Previous attempts to quantify hemodynamic studies of platelet deposition have been limited to 2D geometries. This study provides a physiologic assessment of the effects of stent geometry on platelet deposition by using actual 3D stents. Human blood with fluorescently labeled platelets was circulated through an in vitro system producing physiologic pulsatile flow in a compliant tube in which Bx Velocity, Wallstent and Aurora stents were implanted. Computational fluid dynamic models of the stents provided flow data to aid in explaining localized platelet deposition. Regions of constant flow separation proximal and distal to the strut exhibited very low platelet deposition. Platelet deposition was highest just downstream of flow stagnation regions due to convection towards the wall, then decreased with axial distance from the strut as flow streamlines became locally parallel to the wall. The nearly helically recirculating regions near the Bx Velocity stent connectors exhibited complex fluid dynamics with more platelet deposition, than the smaller separation regions. Localized platelet deposition was heavily dependent on flow convection, suggesting that arterial reaction to stents can be modulated in part by altering the hemodynamics associated with stent design.

Blood flow in stented arteries: a parametric comparison of strut design patterns in three dimensions.

BACKGROUND: Restenosis after stent implantation varies with stent design. Alterations in secondary flow patterns and wall shear stress (WSS) can modulate intimal hyperplasia via their effects on platelet and inflammatory cell transport toward the wall, as well as direct effects on the endothelium. METHOD OF APPROACH: Detailed flow characteristics were compared by estimating the WSS in the near-strut region of realistic stent designs using three-dimensional computational fluid dynamics (CFD), under pulsatile high and low flow conditions. The stent geometry employed was characterized by three geometric parameters (axial strut pitch, strut amplitude, and radius of curvature), and by the presence or lack of the longitudinal connector. RESULTS: Stagnation regions were localized around stent struts. The regions of low WSS are larger distal to the strut. Under low flow conditions, the percentage restoration of mean axial WSS between struts was lower than that for the high flow by 10-12%. The largest mean transverse shear stresses were 30-50% of the largest mean axial shear stresses. The percentage restoration in WSS in the models without the longitudinal connector was as much as 11% larger than with the connector The mean axial WSS restoration between the struts was larger for the stent model with larger interstrut spacing. CONCLUSION: The results indicate that stent design is crucial in determining the fluid mechanical environment in an artery. The sensitivity of flow characteristics to strut configuration could be partially responsible for the dependence of restenosis on stent design. From a fluid dynamics point of view, interstrut spacing should be larger in order to restore the disturbed flow; struts should be oriented to the flow direction in order to reduce the area of flow recirculation. Longitudinal connectors should be used only as necessary, and should be parallel to the axis. These results could guide future stent designs toward reducing restenosis.

Spatial distribution of platelet deposition in stented arterial models under physiologic flow.

This paper presents dynamic flow experiments with fluorescently labeled platelets to allow for spatial observation of wall attachment in inter-strut spacings, to investigate their relationship to flow patterns. Human blood with fluorescently labeled platelets was circulated through an in vitro system that produced physiologic pulsatile flow in a parallel plate flow chamber that contained three different stent designs that feature completely recirculating flow, partially recirculating flow (intermediate strut spacing), and completely reattached flow. Highly resolved spatial distribution of platelets was obtained by imaging fluorescently labeled platelets between the struts. Platelet deposition was higher in areas where flow is directed towards the wall, and lower in areas where flow is directed away from the wall. Flow detachment and reattachment points exhibited very low platelet deposition. Platelet deposition within intermediate strut spacing continued to increase throughout the experimental period, indicating that the deposition rate had not plateaued unlike other strut spacings. The spatial uniformity and temporal increase in platelet deposition for the intermediate strut spacing confirms and helps explain our previous finding that platelet deposition was highest with this strut spacing. Further experimental investigations will include more complex three-dimensional geometries.