cell-labeling-targeting-with-superparamagnetic-iron-oxide

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 ...

ferromagnetic-bare-metal-stent-for-endothelial-cell-capture

Ferromagnetic Bare Metal Stent for Endothelial Cell Capture and Retention

Rapid endothelialization of cardiovascular stents is needed to reduce stent thrombosis and to avoid anti-platelet therapy which can reduce bleeding risk. ...

fabrication-small-caliber-stent-grafts-using-electrospinning-balloon

Fabrication of Small Caliber Stent-grafts Using Electrospinning and Balloon Expandable Bare Metal Stents

Stent-grafts are widely used for the treatment of various conditions such as aortic lesions, aneurysms, emboli due to coronary intervention procedures and ...

proximal-cadaveric-femur-preparation-for-fracture-strength-testing

Proximal Cadaveric Femur Preparation for Fracture Strength Testing and Quantitative CT-based Finite Element Analysis

Cadaveric fracture testing is routinely used to understand factors that affect proximal femur strength.  Because ex vivo biological tissues are prone to ...

method-instrumented-fixture-for-femoral-fracture-testing-sideways

Method and Instrumented Fixture for Femoral Fracture Testing in a Sideways Fall-on-the-Hip Position

Mechanical testing of femora brings valuable insights into understanding the contribution of clinically-measureable variables such as bone mineral density ...

a-method-to-estimate-cadaveric-femur-cortical-strains-during-fracture

A Method to Estimate Cadaveric Femur Cortical Strains During Fracture Testing Using Digital Image Correlation

This protocol describes the method using digital image correlation to estimate cortical strain from high speed video images of the cadaveric femoral ...

characterization-blood-outgrowth-endothelial-cells-boec-from-porcine

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, ...

Mayo Clinic

Computational fluid dynamics (CFD) has become a cutting-edge tool for investigating hemodynamic dysfunctions in the body. It has the potential to help physicians quantify in more detail the phenomena difficult to capture with in vivo imaging techniques. CFD simulations in anatomically realistic geometries pose challenges in generating accurate solutions due to the grid distortion that may occur when the grid is aligned with complex geometries. In addition, results obtained with computational methods should be trusted only after the solution has been verified on multiple high-quality grids. The objective of this study was to present a comprehensive solution verification of the intra-aneurysmal flow results obtained on different morphologies of patient-specific cerebral aneurysms. We chose five patient-specific brain aneurysm models with different dome morphologies and estimated the grid convergence errors for each model. The grid convergence errors were estimated with respect to an extrapolated solution based on the Richardson extrapolation method, which accounts for the degree of grid refinement. For four of the five models, calculated velocity, pressure, and wall shear stress values at six different spatial locations converged monotonically, with maximum uncertainty magnitudes ranging from 12% to 16% on the finest grids. Due to the geometric complexity of the fifth model, the grid convergence errors showed oscillatory behavior; therefore, each patient-specific model required its own grid convergence study to establish the accuracy of the analysis.

Grid convergence errors in hemodynamic solution of patient-specific cerebral aneurysms.

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.

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

Rapid healing of vascular stents is important for avoiding complications associated with stent thrombosis, restenosis, and bleeding related to antiplatelet drugs. Magnetic forces can be used to capture iron-labeled endothelial cells immediately following stent implantation, thereby promoting healing. This strategy requires the development of a magnetic stent that is biocompatible and functional. We designed a stent from the weakly ferromagnetic 2205 stainless steel using finite element analysis. The final design exhibited a principal strain below the fracture limit of 30% during crimping and expansion. Ten stents were fabricated and validated experimentally for fracture resistance. Another 10 stents magnetized with a neodymium magnet showed a magnetic field in the range of 100-750 mG. The retained magnetism was sufficiently strong to capture magnetically-labeled endothelial cells on the stent surfaces during in vitro studies. Magnetically-labeled endothelial cell capture was also verified in vivo after 7 days following coronary implantation in 4 pigs using histological analysis. Images of the stented blood vessels showed uniform endothelium formation on the stent surfaces. In conclusion, we have designed a ferromagnetic bare metal stent from 2205 stainless steel that is functional, biocompatible, and able to capture and retain magnetically-labeled endothelial cells in order to promote rapid stent healing.

Design and validation of a novel ferromagnetic bare metal stent capable of capturing and retaining endothelial cells.

The aim of the present study was to compare proximal femur strength and stiffness obtained experimentally with estimations from Finite Element Analysis (FEA) models derived from Quantitative Computed Tomography (QCT) scans acquired at two different scanner settings. QCT/FEA models could potentially aid in diagnosis and treatment of osteoporosis but several drawbacks still limit their predictive ability. One potential reason is that the models are still sensitive to scanner settings which could lead to changes in assigned material properties, thus limiting their results accuracy and clinical effectiveness. To find the mechanical properties we fracture tested 44 proximal femora in a sideways fall-on-the-hip configuration. Before testing, we CT scanned all femora twice, first at high resolution scanner settings, and second at low resolution scanner settings and built 88 QCT/FEA models of femoral strength and stiffness. The femoral set neck bone mineral density, as measured by DXA, uniformly covered the range from osteoporotic to normal. This study showed that the femoral strength and stiffness values predicted from high and low resolution scans were significantly different (p<0.0001). Strength estimated from high resolution QCT scans was larger for osteoporotic, but smaller for normal and osteopenic femora when compared to low resolution scans. In addition, stiffness estimated from high resolution scans was consistently larger than stiffness obtained from low resolution scans over the entire femoral dataset. While QCT/FEA techniques hold promise for use in clinical settings we provided evidence that further improvements are required to increase robustness in their predictive power under different scanner settings and modeling assumptions.

Quantitative computed tomography-based finite element analysis predictions of femoral strength and stiffness depend on computed tomography settings.

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Magnetizable stent-grafts enable endothelial cell capture.

Incomplete endothelialization of intracoronary stents has been associated with stent thrombosis and recurrent symptoms, whereas prolonged use of dual antiplatelet therapy increases bleeding-related adverse events. Facilitated endothelialization has the potential to improve clinical outcomes in patients who are unable to tolerate dual antiplatelet therapy. The objective of this study was to demonstrate the feasibility of magnetic cell capture to rapidly endothelialize intracoronary stents in a large animal model. A novel stent was developed from a magnetizable duplex stainless steel (2205 SS). Polylactic-co-glycolic acid and magnetite (FeO) were used to synthesize biodegradable superparamagnetic iron oxide nanoparticles, and these were used to label autologous blood outgrowth endothelial cells. Magnetic 2205 SS and nonmagnetic 316L SS control stents were implanted in the coronary arteries of pigs (n = 11), followed by intracoronary delivery of magnetically labeled cells to 2205 SS stents. In this study, we show extensive endothelialization of magnetic 2205 SS stents (median 98.4% cell coverage) within 3 days, whereas the control 316L SS stents exhibited significantly less coverage (median 48.9% cell coverage, p < 0.0001). This demonstrates the ability of intracoronary delivery of magnetic nanoparticle labeled autologous endothelial cells to improve endothelialization of magnetized coronary stents within 3 days of implantation.

Nanoparticle-Mediated Cell Capture Enables Rapid Endothelialization of a Novel Bare Metal Stent.

Commercially available heart valves have many limitations, such as a lack of re-modeling, risk of calcification and thromboembolic problems. Many state-of-the-art tissue engineered heart valves rely on recellularization. Current in vitro testing is insufficient in characterizing a soon to be living valve. It is imperative to understand the performance of an in situ valve, but due to the complex in vivo environment this is difficult to accomplish. Finite element analysis has become a standard tool for modeling mechanical behavior of heart valves; yet, research to date has mostly focused on commercial valves. The purpose of this study has been to develop finite element models of a decellularized and recellularized tissue engineered heart valve. Mechanical properties from porcine aortic valves were utilized to develop finite element models, which were run through a full physiological cardiac cycle. Maximum principal stresses and strains from the leaflets and commissures were analyzed. The results of this study demonstrate that the explanted tissues had reduced mechanical strength compared to the implants but were similar to the native tissues. For the finite element models the explanted recellularized leaflets showed lower stress but increased compliance in the leaflet belly compared to native tissues and higher compliance than implant tissues. Histology demonstrated recellularization and remodeling although remodeled collagen had no clear directionality. In conclusion, we observed successful recellularization and remodeling of the tissue, however, the mechanical response indicates the further remodeling is required following implantation in the aortic/pulmonary position.

In Silico Performance of a Recellularized Tissue Engineered Transcatheter Aortic Valve.

The purpose of the work presented here was to establish an experimental testing configuration that would generate a bending compression fracture in a laboratory setting. To this end, we designed and fabricated a fixture to accommodate a three level spine segment and to be able to perform mechanical testing by applying an off-centric compressive loading to create a flexion-type motion. Forces and moments occurring during testing were measured with a six-channel load cell. The initial testing configuration (Fixture A) included plates connected to the superior potted vertebral body and to the ball-socket joint of the testing system ram. Surprisingly, while all cadaveric specimens underwent a similar off-centric compressive loading, most of the specimens showed extension outcomes as opposed to the intended pure-flexion motion. The extension was due to fixture size and weight; by applying an off-centric load directly on the top plate, unintended large shear forces were generated. To resolve the issue, several modifications were made to the original fixture configuration. These modifications included the removal of the superior plates and the implementation of wedges at the superior surface of the fixture (Fixture B). A synthetic sample was used during this modification phase to minimize the number of cadaveric specimens while optimizing the process. The best outcomes were consistently observed when a 15°-wedge was used to provide flexion-type loading. Cadaveric specimens were then experimentally tested to fracture using the modified testing configuration (Fixture B). A comparison between both fixtures, A and B, revealed that almost all biomechanical parameters, including force, moment, and displacement data, were affected by the testing setup. These results suggest that fixture design and implementation for testing is of extreme importance, and can influence the fracture properties and affect the intended motion.

Mechanical testing setups affect spine segment fracture outcomes.

Computational fluid dynamics (CFD) has grown as a tool to help understand the hemodynamic properties related to the rupture of cerebral aneurysms. Few of these studies deal specifically with aneurysm growth and most only use a single time instance within the aneurysm growth history. The present retrospective study investigated four patient-specific aneurysms, once at initial diagnosis and then at follow-up, to analyze hemodynamic and morphological changes. Aneurysm geometries were segmented via the medical image processing software Mimics. The geometries were meshed and a computational fluid dynamics (CFD) analysis was performed using ANSYS. Results showed that major geometry bulk growth occurred in areas of low wall shear stress (WSS). Wall shape remodeling near neck impingement regions occurred in areas with large gradients of WSS and oscillatory shear index. This study found that growth occurred in areas where low WSS was accompanied by high velocity gradients between the aneurysm wall and large swirling flow structures. A new finding was that all cases showed an increase in kinetic energy from the first time point to the second, and this change in kinetic energy seems correlated to the change in aneurysm volume.

Morphological and Hemodynamic Changes during Cerebral Aneurysm Growth.

In breast radiology, ultrasound detection of biopsy markers or clips for localization purposes is often challenging, especially in the axilla. The purpose of this research was to test the hypothesis that the surface roughness of biopsy clips would elicit a twinkling signature on color Doppler, making them more readily identifiable by ultrasound. Ultrasound color Doppler imaging of 12 biopsy markers was performed and consensus scoring of the degree of twinkling (0 [no twinkling] to 4 [exuberant twinkling]) was obtained for each of the markers. The surface roughness characteristics of the markers were measured using 3-D coherence scanning interferometry. The 3 markers scoring at least 3 for twinkling in vitro were cork, Q and Vision. Of these 3 markers, only the cork marker scored a 4 ex vivo and in cadaveric tissue. Surface roughness metrics demonstrated a positive estimated correlation with the twinkling scores (rho = 0.33, 95% CI = [-0.48 to 0.84]). Of the 12 markers tested, the markers that twinkled corresponded to surface roughness measured with non-contact 3-D optical imaging. Qualitatively, lower color scales and color frequencies optimized twinkling, but the most specific qualitative predictor of confidence in twinkling was insensitivity to changes in color scale and color frequency values.

ArticleTotal : 7	Year
Publication title Cited by 20	2015
Publication title Cited by 12	2015
Publication title Cited by 10	2016
Publication title Cited by 9	2017
Publication title Cited by 3	2017

Article	Year
Grid convergence errors in hemodynamic solution of patient-specific cerebral aneurysms. Journal of biomechanics\| PubMed ID: 23062796	2012
Computational fluid dynamics simulation of an anterior communicating artery ruptured during angiography. BMJ case reports\| PubMed ID: 23475991	2013
Computational fluid dynamics simulation of an anterior communicating artery ruptured during angiography. Journal of neurointerventional surgery\| PubMed ID: 23493342	2014
Design and validation of a novel ferromagnetic bare metal stent capable of capturing and retaining endothelial cells. Annals of biomedical engineering\| PubMed ID: 25138164	2014
Quantitative computed tomography-based finite element analysis predictions of femoral strength and stiffness depend on computed tomography settings. Journal of biomechanics\| PubMed ID: 25442008	2015
Magnetizable stent-grafts enable endothelial cell capture. Journal of magnetism and magnetic materials\| PubMed ID: 28286359	2017
Nanoparticle-Mediated Cell Capture Enables Rapid Endothelialization of a Novel Bare Metal Stent. Tissue engineering. Part A\| PubMed ID: 29431053	2018
In Silico Performance of a Recellularized Tissue Engineered Transcatheter Aortic Valve. Journal of biomechanical engineering\| PubMed ID: 30874717	2019
Mechanical testing setups affect spine segment fracture outcomes. Journal of the mechanical behavior of biomedical materials\| PubMed ID: 31479817	2019
Morphological and Hemodynamic Changes during Cerebral Aneurysm Growth. Brain sciences\| PubMed ID: 33921861	2021
Using Ultrasound Color Doppler Twinkling to Identify Biopsy Markers in the Breast and Axilla. Ultrasound in medicine & biology\| PubMed ID: 34412903	2021

Susheil Uthamaraj

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