Benchtop proof of concept and comparison of iron- and magnesium-based bioresorbable flow diverters.

OBJECTIVE: Bioresorbable flow diverters (BRFDs) could significantly improve the performance of next-generation flow diverter technology. In the current work, magnesium and iron alloy BRFDs were prototyped and compared in terms of porosity/pore density, radial strength, flow diversion functionality, and resorption kinetics to offer insights into selecting the best available bioresorbable metal candidate for the BRFD application. METHODS: BRFDs were constructed with braided wires made from alloys of magnesium (MgBRFD) or iron (FeBRFD). Pore density and crush resistance force were measured using established methods. BRFDs were deployed in silicone aneurysm models attached to flow loops to investigate flow diversion functionality and resorption kinetics in a simulated physiological environment. RESULTS: The FeBRFD exhibited higher pore density (9.9 vs 4.3 pores/mm2) and crush resistance force (0.69 ± 0.05 vs 0.53 ± 0.05 N/cm, p = 0.0765, n = 3 per group) than the MgBRFD, although both crush resistances were within the range previously reported for FDA-approved flow diverters. The FeBRFD demonstrated greater flow diversion functionality than the MgBRFD, with significantly higher values of established flow diversion metrics (mean transit time 159.6 ± 11.9 vs 110.9 ± 1.6, p = 0.015; inverse washout slope 192.5 ± 9.0 vs 116.5 ± 1.5, p = 0.001; n = 3 per group; both metrics expressed as a percentage of the control condition). Last, the FeBRFD was able to maintain its braided structure for > 12 weeks, whereas the MgBRFD was almost completely resorbed after 5 weeks. CONCLUSIONS: The results of this study demonstrated the ability to manufacture BRFDs with magnesium and iron alloys. The data suggest that the iron alloy is the superior material candidate for the BRFD application due to its higher mechanical strength and lower resorption rate relative to the magnesium alloy.

Bioresorbable flow diverters for the treatment of intracranial aneurysms: review of current literature and future directions.

The use of flow diverters is a rapidly growing endovascular approach for the treatment of intracranial aneurysms. All FDA-approved flow diverters are composed of nitinol or cobalt-chromium, which will remain in the patient for the duration of their life. Bioresorbable flow diverters have been proposed by several independent investigators as the next generation of flow diverting devices. These devices aim to serve their transient function of occluding and healing the aneurysm prior to being safely resorbed by the body, eliminating complications associated with the permanent presence of conventional flow diverters. Theoretical advantages of bioresorbable flow diverters include (1) reduction in device-induced thrombosis; (2) reduction in chronic inflammation and device-induced stenosis; (3) reduction in side branch occlusion; (4) restoration of physiological vasomotor function; (5) reduction in imaging artifacts; and (6) use in pediatric applications. Advances made in the similar bioresorbable coronary stenting field highlight some of these advantages and demonstrate the feasibility and safety of bioresorbable endovascular devices in the clinic. The current work aims to review the progress of bioresorbable flow diverters, identify opportunities for further investigation, and ultimately stimulate the advancement of this technology.

Characterization of Blood Outgrowth Endothelial Cells (BOEC) from Porcine Peripheral Blood.

The endothelium is a dynamic integrated structure that plays an important role in many physiological functions such as angiogenesis, hemostasis, inflammation, and homeostasis. The endothelium also plays an important role in pathophysiologies such as atherosclerosis, hypertension, and diabetes. Endothelial cells form the inner lining of blood and lymphatic vessels and display heterogeneity in structure and function. Various groups have evaluated the functionality of endothelial cells derived from human peripheral blood with a focus on endothelial progenitor cells derived from hematopoietic stem cells or mature blood outgrowth endothelial cells (or endothelial colony-forming cells). These cells provide an autologous resource for therapeutics and disease modeling. Xenogeneic cells may provide an alternative source of therapeutics due to their availability and homogeneity achieved by using genetically similar animals raised in similar conditions. Hence, a robust protocol for the isolation and expansion of highly proliferative blood outgrowth endothelial cells from porcine peripheral blood has been presented. These cells can be used for numerous applications such as cardiovascular tissue engineering, cell therapy, disease modeling, drug screening, studying endothelial cell biology, and in vitro co-cultures to investigate inflammatory and coagulation responses in xenotransplantation.

Finite Element Analysis of the Septal Cartilage L-Strut.

Importance: Septoplasty is one of the most commonly performed operations in the head and neck. However, the reasons for septoplasty failure and the additional stress of performing a chondrotomy on the septal cartilage are not well understood. Design, Setting, and Participants: A finite element model of the nasal septum was created using a microcomputed tomography scan of the nasoseptal complex that was reconstructed into a three-dimensional model in silico. Testing included four common chondrotomy designs: traditional L-strut, double-cornered chondrotomy (DCC), curved L-strut, and the C-curve. Tip displacement was applied in a vector parallel to the caudal strut to simulate nasal tip palpation. Main Outcomes and Measures: With finite element analysis, the maximum principal stress (MPS), von Mises stress (VMS), harvested cartilage volume, and surface area were recorded. Results: The highest MPS for the L-strut, DCC, curved L-strut, and C-curve was identified at the corner of the chondrotomy. The MPS at the corner of the chondrotomy was reduced 44% when comparing the C-curve with the traditional L-strut. The VMS patterns showed compressive stress along the caudal septum in all models, but at the corner, the stresses were highest in the chondrotomies designed with sharp-angled corners. The VMS showed a 76% decrease when comparing the C-curve with the traditional L-strut. The stress across the anterior septal angle is also higher in models with sharp-angled corners. Cartilage harvest volumetric and surface area assessments did not show meaningful differences between shapes. Conclusions and Relevance: The highest area of stress is near the transition of the dorsal to caudal septum in all models. Stresses are relatively higher in chondrotomy shapes that contain sharp-angled corners. The relative reduction in MPS and VMS utilizing a C-curve instead of an L-strut may decrease the likelihood that the septum will deform or fail in this region. The volume and surface area of the C-curve are similar to that of the L-strut technique. Avoiding sharp-angled corners reduces the stresses at the corner of the chondrotomy and across the anterior septal angle. Using a C-curve may be an improved septoplasty design.

Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH)-phase II: rupture risk assessment.

PURPOSE: Assessing the rupture probability of intracranial aneurysms (IAs) remains challenging. Therefore, hemodynamic simulations are increasingly applied toward supporting physicians during treatment planning. However, due to several assumptions, the clinical acceptance of these methods remains limited. METHODS: To provide an overview of state-of-the-art blood flow simulation capabilities, the Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH) was conducted. Seventeen research groups from all over the world performed segmentations and hemodynamic simulations to identify the ruptured aneurysm in a patient harboring five IAs. Although simulation setups revealed good similarity, clear differences exist with respect to the analysis of aneurysm shape and blood flow results. Most groups (12/71%) included morphological and hemodynamic parameters in their analysis, with aspect ratio and wall shear stress as the most popular candidates, respectively. RESULTS: The majority of groups (7/41%) selected the largest aneurysm as being the ruptured one. Four (24%) of the participating groups were able to correctly select the ruptured aneurysm, while three groups (18%) ranked the ruptured aneurysm as the second most probable. Successful selections were based on the integration of clinically relevant information such as the aneurysm site, as well as advanced rupture probability models considering multiple parameters. Additionally, flow characteristics such as the quantification of inflow jets and the identification of multiple vortices led to correct predictions. CONCLUSIONS: MATCH compares state-of-the-art image-based blood flow simulation approaches to assess the rupture risk of IAs. Furthermore, this challenge highlights the importance of multivariate analyses by combining clinically relevant metadata with advanced morphological and hemodynamic quantification.

Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles.

Targeted delivery of cells and therapeutic agents would benefit a wide range of biomedical applications by concentrating the therapeutic effect at the target site while minimizing deleterious effects to off-target sites. Magnetic cell targeting is an efficient, safe, and straightforward delivery technique. Superparamagnetic iron oxide nanoparticles (SPION) are biodegradable, biocompatible, and can be endocytosed into cells to render them responsive to magnetic fields. The synthesis process involves creating magnetite (Fe3O4) nanoparticles followed by high-speed emulsification to form a poly(lactic-co-glycolic acid) (PLGA) coating. The PLGA-magnetite SPIONs are approximately 120 nm in diameter including the approximately 10 nm diameter magnetite core. When placed in culture medium, SPIONs are naturally endocytosed by cells and stored as small clusters within cytoplasmic endosomes. These particles impart sufficient magnetic mass to the cells to allow for targeting within magnetic fields. Numerous cell sorting and targeting applications are enabled by rendering various cell types responsive to magnetic fields. SPIONs have a variety of other biomedical applications as well including use as a medical imaging contrast agent, targeted drug or gene delivery, diagnostic assays, and generation of local hyperthermia for tumor therapy or tissue soldering.

Intra-aneurysmal flow rates are reduced by two flow diverters: an experiment using tomographic particle image velocimetry in an aneurysm model.

BACKGROUND: Limitations on treating large, giant, and wide-necked aneurysms with coiling have made flow diverters a promising alternative to current practice by supporting reconstruction of the parent artery. OBJECTIVE: To assess the changes to fluid dynamics within an aneurysm by studying two different endoluminal flow diverters on a simple aneurysm model, using tomographic particle image velocimetry to determine which device would better minimize fluid flow into an aneurysm and observe any significant changes in aneurysm fluid structures. METHODS: Steady velocity fields of the model's aneurysm dome and neck were measured at three inlet velocities (18, 39, and 59 cm/s) for two flow diverter diameters with different porosities and compared against a baseline case with no flow diverter. RESULTS: In the baseline case a large vortex was present inside the dome for all flow rates. However, both devices eliminated this main vortex at all flow rates and reduced the peak aneurysmal velocities by about 90%. A strong correlation between flow diverter porosity and flow reduction was found. In each case the inflow to the aneurysm shifted from the distal neck to the mid- or proximal neck after flow diverter placement. CONCLUSIONS: Even with this relatively simple experimental setup, we were able to observe the major flow field changes, which occurred immediately after the deployment of each flow diverter. Limitations of the study included a simplified geometry and steady-state flow. Constraints included model making and limited availability of flow diverters.

Computational fluid dynamics simulation of an anterior communicating artery ruptured during angiography.

We present a computational fluid dynamics (CFD) analysis of the hemodynamic environment of an anterior communicating artery that spontaneously ruptured immediately following three-dimensional rotational angiography. Subsequent digital subtraction angiography allowed for the localization of the point of rupture within the aneurysm dome. CFD analysis demonstrated a concentrated jet that impinged directly at the site of rupture. Peak systolic pressure and wall shear stress were both maximal near the rupture location.