Publications

First Prize: Evaluation of the Tensile Strength of the Human Ureter—Preliminary Results

The circumferential tensile strength of the ureter was found to be significantly lower than the longitudinal strength. Circumferential tensile strength was also lower with more proximal parts of the ureter. This information may be important for the design of "intelligent" devices and simulators to prevent complications.

EFFECTS OF DIMINISHED PULSATILE PERFUSION ON THE MECHANICAL PROPERTIES AND VASO-RESPONSE OF BOVINE LEFT EXTERNAL CAROTID ARTERY

The purpose of this work was to test the effects of diminished pulse on the mechanical properties and vasoresponse of bovine arteries. A segment was harvested at the time of implant of a continuous flow ventricular assist device. The goal was to maintain pump flow ∼ 50% of cardiac output. Another segment was removed at necropsy (after 30 days). The vessels were implanted into an ex-vivo perfusion system. Compliance was assessed by measuring external diameter change over a pressure pulse (P = 120/80 mmHg). The vessels were then tested to failure in a tensile testing device. Young's modulus, yield strength, and ultimate strength were derived from the data. The results of the work do not indicate a statistically significant change in vasoresponse or mechanical properties between arteries removed at baseline and at necropsy from the pump-implanted animals. However, the data suggests several trends occurring in the pump-implanted: the compliance (C) decreases (p < 0.25) the ultimate strength (US) of the tissue increases (p < 0.18) and the % constriction increases (p < 0.25). Statistical comparisons were also made between controls (n=2) and the implanted cows (n=7) at necropsy. The C in the controls is greater than in the implants (p < 0.06) The US of the arteries taken from the implanted cows is significantly greater than the sham controls at necropsy (p < 0.05). Further research i s required to verify if these observed trends are indeed significant.

Modeling in cardiovascular biomechanics

Mesenchymal Progenitor Cells Differentially Respond to Mechanical Stimulation: Morphology, Proliferation, Gene and Protein Expression

Mechanical stimulation has been shown to regulate gene and protein expression in many cell types, including stem cells. Cyclic strain has been previously shown by our laboratory and others [1, 2] to regulate smooth muscle gene and protein expression in mesenchymal progenitor cells (MPCs). From these and other results [3], we hypothesize that the differentiated phenotype of MPCs may be controlled by the appropriate type, magnitude, and frequency of mechanical stimulation. We describe here the differential response of MPCs to three mechanical stimuli — cyclic strain, cyclic hydrostatic pressure, and laminar shear stress — over a range of magnitudes and frequencies that are consistent with the cardiovascular system.

Biaxial Mechanical Behavior of Aneurysmal and Nonaneurysmal Human Abdominal Aorta: Preliminary Results

Abstract Rupture of abdominal aortic aneurysm (AAA) is currently the 13th leading cause of death in the US and represents a mechanical failure of the diseased aortic wall. Therefore, accurate estimation of the wall stress distribution in AAA may be a clinically useful tool to predict their risk of rupture [1]. A necessary precursor to an accurate stress analysis is an appropriate representation of the constitutive behavior of the AAA wall. Many previous biomechanical analyses of AAA have employed a linearly elastic constitutive behavior [2,3]. However, we have shown that the AAA wall is nonlinearly elastic [4] and undergoes large strain in-vivo [5]. With this as motivation, we recently developed an isotropic, nonlinearly elastic, large strain constitutive model for AAA wall based on uniaxial tensile testing data [6]. The assumption of isotropy was not validated, however. Utilization of an isotropic material symmetry in models of anisotropic structures may lead to significant errors in stress distribution [7]. Indeed, experiments suggest that the nonaneurysmal aorta is anisotropic (orthotropic) [8,9], but the material symmetry of AAA is not presently known. Moreover, most of the previous work investigating the material symmetry of aorta has been performed on animal tissue. To evaluate the anisotropy of aortic tissue, biaxial experimentation is necessary. There has been very little published work involving the biaxial experimentation of human aortic tissue, and none for AAA tissue. We present here a preliminary evaluation of the biaxial mechanical behavior of human aneurysmal and nonaneurysmal abdominal aorta.

Fiber micro-architecture in the longitudinal-radial and circumferential-radial planes of ascending thoracic aortic aneurysm media

Effects of uniaxial cyclic strain on adipose-derived stem cell morphology, proliferation, and differentiation

1375: Contributions of Collagen and Elastin to Urethral Biomechanics: Correlation of Damaged Elastin to Stress Urinary Incontinence Induced by Birth Trauma

You have accessJournal of UrologyPodium 41, Tuesday, May 22, 2007, 10:00 am - 12:00 pm1 Apr 20071375: Contributions of Collagen and Elastin to Urethral Biomechanics: Correlation of Damaged Elastin to Stress Urinary Incontinence Induced by Birth Trauma Rachelle L. Prantif, William C. de Groat, Donna J. Haworth, Ronald J. Jankowski, Michael B. Chancellor, Naoki Yoshimura, and David Vorp Rachelle L. PrantifRachelle L. Prantif More articles by this author , William C. de GroatWilliam C. de Groat More articles by this author , Donna J. HaworthDonna J. Haworth More articles by this author , Ronald J. JankowskiRonald J. Jankowski More articles by this author , Michael B. ChancellorMichael B. Chancellor More articles by this author , Naoki YoshimuraNaoki Yoshimura More articles by this author , and David VorpDavid Vorp More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)31589-1AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1375: Contributions of Collagen and Elastin to Urethral Biomechanics: Correlation of Damaged Elastin to Stress Urinary Incontinence Induced by Birth Trauma." The Journal of Urology, 177(4S), pp. 453–454 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 177Issue 4SApril 2007Page: 453-454 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Rachelle L. Prantif More articles by this author William C. de Groat More articles by this author Donna J. Haworth More articles by this author Ronald J. Jankowski More articles by this author Michael B. Chancellor More articles by this author Naoki Yoshimura More articles by this author David Vorp More articles by this author Expand All Advertisement PDF DownloadLoading ...

An Experimental and Numerical Comparison of the Rupture Locations of an Abdominal Aortic Aneurysm

According to these experimental and numerical findings, AAAs experience higher stresses at regions of inflection compared to regions of maximum diameter. Ruptures of the idealized silicone models occurred predominantly at the inflection points, as numerically predicted. Regions of inflection can be easily identified from basic 3-dimensional reconstruction; as ruptures appear to occur at inflection points, these findings may provide a useful insight into the clinical significance of inflection regions. This approach will be applied to patient-specific models in a future study.

Characterization of Isolated Urethral Smooth Muscle Cells and Their Incorporation Into a Tissue Engineered Urethral Wrap

Millions of people worldwide suffer from an involuntary leakage of urine, a condition known as urinary incontinence. In the US alone, the estimated cost of managing this is more than $16 billion [1]. Stress urinary incontinence (SUI), the most common form, is characterized by involuntary leakage of urine from effort or exertion during actions such as laughing, coughing, or sneezing. SUI largely occurs as a result of weak or damaged pelvic muscles that support the bladder and urethra, which makes the urethra unable to maintain its seal and allows urine to leak. Current SUI treatments such as pelvic floor muscle training, vaginal inserts, pharmacologic therapeutics, and surgical procedures are limited by ineffectiveness and/or subsequent complications [2, 3].

“Attractive” Treatment for Abdominal Aortic Aneurysm Repair: Magnetic Localization of Silk-Iron Packaged Extracellular Vesicles

Abdominal aortic aneurysm (AAA) is a dilatation of the distal aorta to a diameter of 50% or more of its normal size of about 2 cm. Risk of aortic rupture can be nearly eliminated with either open surgery or endovascular repair. Procedural risks limit the value of these interventions unless the diameter of the aneurysm has reached a critical threshold (established as 5.5 cm in men or 5.0 cm in women). Thus, patients are monitored until this threshold is reached. Approximately 80% of small AAA will grow and exceed the threshold, providing a therapeutic window for altering this natural history and reducing the risk of rupture. Previous work in our lab has utilized adipose-derived mesenchymal stem cells (ASCs) to treat AAA in vivo, preserving elastic fibers and slowing aneurysm expansion. This work sought to create a delivery system for therapeutic extracellular vesicles (ASC-EVs) secreted by ASCs. Our delivery system incorporated the biocompatibility of regenerated silk fibroin (RSF), the magnetic moveability of iron oxide nanoparticles (IONPs), and the regenerative nature of ASC-EVs to create silk-iron packaged extracellular vesicles (SIPEs). Using this system, we tested the ability to magnetically localize the SIPEs and release their encapsulated ASC-EVs to exert their regenerative effects in vitro. We were successful in magnetically localizing the SIPEs in vitro and silk-iron microparticles (SIMPs) in vivo and in detecting their releasates via flow cytometry and cellular uptake assays. However, while their releasates were detected, their biological effects were diminished compared to unencapsulated controls. Thus, additional optimization related to loading efficiency is needed.

Mechanical wall stress in abdominal aortic aneurysm: Influence of diameter and asymmetry

Abstract Th0006: Clickable Extracellular Vesicles for Localized Abdominal Aortic Aneurysm Repair

Introduction: Abdominal aortic aneurysm (AAA) features a degradative environment and loss of vascular elastin, which we believe could be treated with an engineered regenerative therapy. Our group and others have investigated using mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) for regeneration, but a key barrier to successful implementation is delivery. To address this problem, we have developed an EV delivery system that utilizes click chemistry to improve EV retention within a hydrogel. Hypothesis: Click-bound EVs will have better retention within hydrogels compared to non-clicked EVs. Methods: MSCs were cultured with or without Ac4ManNAz to metabolize an azido tag onto the EVs. After isolation the EVs were labeled with NHs-Cy5 and excess dye was removed by dialysis. DBCO-conjugated fibrinogen and collagen were mixed to form a “hybridgel” with different release characteristics depending on the concentration of each protein. The final concentration of the gel was 7.5 mg/mL with the DBCO collagen gel being a 2:1 mixture with WT collagen and the hybridgel being a 50:50 mixture of collagen and fibrinogen. EVs were characterized by Western blot and nanoparticle tracking analysis. EVs were co-cultured with SMCs in fibrin gels for 6h to assess EV uptake. Results and Conclusions: DBCO-conjugated collagen and fibrinogen had better EV retention than their wild type counterparts. Collagen had better retention compared to fibrinogen, and the hybridgel had a retention profile between the two. Co-culture of EVs with fibrin gels demonstrated uptake into SMCs compared to dye controls. Conclusions/Interpretations: A hybridgel of collagen and fibrinogen can be used to tailor retention. EVs can be taken up by SMCs in 3D fibrin constructs.

Age-Related Differences in the Biaxial Biomechanical Behavior of Human Abdominal Aorta

The biomechanical response of abdominal aortic tissue to uniaxial loading conditions has been reported previously [1]. This testing identified the uniaxial mechanical response of aortic tissue to specimens oriented in the longitudinal and circumferential directions, but did not provide significant evidence for the isotropy or anisotropy of this tissue. The information taken from uniaxial tensile testing is insufficient for the characterization of the multi-axial mechanical response of aortic tissue. In particular, the uniaxial response of a biological tissue in a given direction does not incorporate the effects of loading in an orthogonal direction. For these reasons, there exists a need for an enhanced description of the mechanical response of aortic tissue to loading in multiple planar directions. For the current investigation, biaxial tensile testing was performed on normal abdominal aortic tissue in order to gain insight into the anisotropy and age related differences of the biomechanical response of this tissue.

An Experimental System to Expose Perfused Vascular Segments to Cyclic Bending Ex-Vivo

Abstract Portions of coronary and other blood vessels undergo cyclic bending due to attachment to the heart or crossing of joints [1,4,9]. Bending of a vascular segment alters the local transmural stresses and strains [5,13] as well as the shear stresses acting on the endothelial surface [8,11]. Fluctuations in both shear stress and in-plane stretch have been shown to influence endothelial cell and smooth muscle cell biology [12]. The purpose of the present work was to create a model to expose perfused, intact vascular segments to cyclic bending in-vitro. Such a system would enable the assessment of the biologic response of vascular tissue to combined alterations in transmural stress and shear stress produced by cyclic bending.

A Custom Image-Based Analysis Tool for Quantifying Elastin and Collagen Fiber Micro-Architecture in the Wall of the Human Aorta From Multi-Photon Microscopy Images

The two primary load-bearing components of the connective fiber micro-architecture of aorta are the proteins elastin and collagen. The structure of elastin and collagen fibers is important to support the proper function of the aorta, and alteration of the quantity and/or arrangement of these fibers can lead to mechanical and functional changes associated with aortic disease. Therefore, an adequate quantification of the micro-architecture of elastin and collagen fibers in the aortic wall would provide insight into the influence of micro-architecture on the biomechanical response of the aorta in health and disease.

Development and 3D Finite Element Implementation of a Multiaxial Constitutive Relation for Abdominal Aortic Aneurysms

Abdominal aortic aneurysm (AAA), a localized dilation of the infrarenal aorta, represents a significant disease in the western population. There are approximately 200,000 patients in the US and 500,000 patients worldwide diagnosed with AAAs every year (Bosch, et al. 2001), and rupture of AAAs currently ranks as the 13th leading cause of death in the US. (Silverberg and Lubera 1987) In the past 30 years, the diagnosis of AAA has tripled in the Western world, and this will likely increase in the coming years as the average age of the population is increasing. (Bosch, et al. 2001)

Extracellular Vesicles Enhance the Remodeling of Cell-Free Silk Vascular Scaffolds in Rat Aortae

Vascular tissue engineering is aimed at developing regenerative vascular grafts to restore tissue function by bypassing or replacing defective arterial segments with tubular biodegradable scaffolds. Scaffolds are often combined with stem or progenitor cells to prevent acute thrombosis and initiate scaffold remodeling. However, there are limitations to cell-based technologies regarding safety and clinical translation. Extracellular vesicles (EVs) are nanosized particles released by most cell types, including stem and progenitor cells, that serve to transmit protein and RNA cargo to target cells throughout the body. EVs have been shown to replicate the therapeutic effect of their parent cells; therefore, EVs derived from stem or progenitor cells may serve as a more translatable, cell-free, therapeutic base for vascular scaffolds. Our study aims to determine if EV incorporation provides a positive effect on graft patency and remodeling <i>in vivo</i>. We first assessed the effect of human adipose-derived mesenchymal stem cell (hADMSC) EVs on vascular cells using <i>in vitro</i> bioassays. We then developed an EV-functionalized vascular graft by vacuum-seeding EVs into porous silk-based tubular scaffolds. These constructs were implanted as aortic interposition grafts in Lewis rats, and their remodeling capacity was compared to that observed for hADMSC-seeded and blank (non-seeded) controls. The EV group demonstrated improved patency (100%) compared to the hADMSC (56%) and blank controls (82%) following eight weeks <i>in vivo</i>. The EV group also produced significantly more elastin (126.46%) and collagen (44.59%) compared to the blank group, while the hADMSC group failed to produce significantly more elastin (57.64%) or collagen (11.21%) compared to the blank group. Qualitative staining of the explanted neo-tissue revealed improved endothelium formation, increased smooth muscle cell infiltration, and reduced macrophage numbers in the EV group compared to the controls, which aids in explaining this group's favorable pre-clinical outcomes.

Local Quantification of Wall Thickness and Intraluminal Thrombus Offer Insight into the Mechanical Properties of the Aneurysmal Aorta