Marisa Bazzi

All Publications

• Alterations in ascending aortic hemodynamics and aortic length correlate with sex-specific thoracic aortic aneurysm dilation and lifespan in a mouse model of severe Marfan syndrome. Computers in biology and medicine Dwivedi, K. K., Wu, Y., Bazzi, M. S., Wiputra, H., Rother, J., Quirk, J. D., Barocas, V. H., Wagenseil, J. E. 2026; 205: 111594

  Abstract

  Thoracic aortic aneurysm (TAA) is a dilation of the aorta that may eventually dissect and/or rupture. It is associated with genetic disorders such as Marfan syndrome (MFS) and is a life-threatening cardiovascular condition if left untreated. Current clinical guidelines for TAA management are primarily based on maximum diameter thresholds that are often inadequate, particularly in MFS patients. Moreover, the diameter thresholds are not sex-specific, despite growing evidence that TAA outcomes in MFS are influenced by sex. The aim of this study was to identify non-invasive biomarkers for better management of TAA using male and female mice that are a genetic model of severe MFS and their littermate controls. Fluid-structure interaction (FSI) simulations were performed to assess aortic geometry, hemodynamics, and wall mechanical stresses during TAA progression (as measured by aortic dilation) and outcomes (as measured by mouse lifespan). Oscillatory shear index (OSI) correlated significantly with TAA progression in males, but not females, while time averaged wall shear stress (TAWSS) correlated significantly with TAA progression in females, but not males. Endothelial cell activation potential (ECAP), a metric that combines OSI and TAWSS, was significantly correlated with TAA progression in both sexes and had the strongest correlation with lifespan of all hemodynamic metrics. The geometric metric of aortic elongation ratio (AER) (i.e. length) also had strong correlations with TAA progression and lifespan in male and female mice. This study demonstrates that hemodynamic and geometric metrics hold promise as non-invasive biomarkers for personalized management of TAA in MFS.

  View details for DOI 10.1016/j.compbiomed.2026.111594

  View details for PubMedID 41775185

• Computational Analysis of Flow and Transport Suggests Reduced Oxygen Levels Within Intracranial Aneurysms, Especially in Individuals With Sickle-Cell Disease JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME Bazzi, M. S., Wiputra, H., Wood, D. K., Barocas, V. H. 2025; 147 (2)

  Abstract

  Sickle cell disease (SCD) is a genetic condition characterized by an abundance of sickle hemoglobin in red blood cells. SCD patients are more prone to intracranial aneurysms (ICA) compared to the general population, with distinctive features such as multiple intracranial aneurysms: 66% of SCD patients with ICAs have multiples ICAs, compared to 20% in nonsickle patients. The exact mechanism behind these associations is not fully understood, but there is a hypothesized link between hypoxic conditions in blood vessels and impaired synthesis of extracellular matrix, which may weaken the vessel walls, favoring aneurysm formation and rupture. SCD patients experience reduced oxygen levels in their blood, potentially exacerbating hypoxia in intracranial aneurysms, and potentially creating a feedback loop that could contribute to aneurysm development and early onset in these patients. In this work, we performed a series of computational studies (Fluent) using idealized geometries to investigate the key differences in the oxygen transport and blood flow dynamics inside an aneurysm formation for sickle and nonsickle cases. We found that using sickle cell disease parameters resulted in a 14% to 68% reduction in blood flow and a 37% to 70% reduction in oxygen availability within the aneurysm, depending on the vessel curvature and the aneurysm throat diameter, due to factors including oxygen-dependent viscosity and alteration in the oxygen transport. The results indicate that depending on geometry and flow characteristics, some degree of hypoxia maybe present in aneurysm bulb and would be more severe in sickle-cell disease patients. This study hopes to bring into attention the potential presence of hypoxic environment in the aneurysm bulb.

  View details for DOI 10.1115/1.4067323

  View details for Web of Science ID 001391606300002

  View details for PubMedID 39636010

  View details for PubMedCentralID PMC11748962

• A novel perfusion bioreactor promotes the expansion of pluripotent stem cells in a 3D-bioprinted tissue chamber BIOFABRICATION Komosa, E. R., Lin, W., Mahadik, B., Bazzi, M. S., Townsend, D., Fisher, J. P., Ogle, B. M. 2024; 16 (1)

  Abstract

  While the field of tissue engineering has progressed rapidly with the advent of 3D bioprinting and human induced pluripotent stem cells (hiPSCs), impact is limited by a lack of functional, thick tissues. One way around this limitation is to 3D bioprint tissues laden with hiPSCs. In this way, the iPSCs can proliferate to populate the thick tissue mass prior to parenchymal cell specification. Here we design a perfusion bioreactor for an hiPSC-laden, 3D-bioprinted chamber with the goal of proliferating the hiPSCs throughout the structure prior to differentiation to generate a thick tissue model. The bioreactor, fabricated with digital light projection, was optimized to perfuse the interior of the hydrogel chamber without leaks and to provide fluid flow around the exterior as well, maximizing nutrient delivery throughout the chamber wall. After 7 days of culture, we found that intermittent perfusion (15 s every 15 min) at 3 ml min-1provides a 1.9-fold increase in the density of stem cell colonies in the engineered tissue relative to analogous chambers cultured under static conditions. We also observed a more uniform distribution of colonies within the tissue wall of perfused structures relative to static controls, reflecting a homogeneous distribution of nutrients from the culture media. hiPSCs remained pluripotent and proliferative with application of fluid flow, which generated wall shear stresses averaging ∼1.0 dyn cm-2. Overall, these promising outcomes following perfusion of a stem cell-laden hydrogel support the production of multiple tissue types with improved thickness, and therefore increased function and utility.

  View details for DOI 10.1088/1758-5090/ad084a

  View details for Web of Science ID 001099761400001

  View details for PubMedID 37906964

  View details for PubMedCentralID PMC10636629

• Computational and experimental comparison on the effects of flow-induced compression on the permeability of collagen gels JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS Vidmar, C. S., Bazzi, M., Lai, V. K. 2022; 128: 105107

  Abstract

  Collagen is a naturally occurring polymer and is popular in tissue engineering due to its high biocompatibility, ubiquity throughout the body, and its porous nature. The transport properties of collagen help dictate the delivery of nutrients to tissues, and the mechanical properties can help improve the function of engineered tissues. The objective of this study is to investigate experimentally the change in permeability as collagen gels undergo flow-induced compression and compare these results with model predictions using a finite element model. We developed a horizontal apparatus to measure the hydraulic permeability of collagen gels undergoing flow-induced compression. The permeability of 1.98 mg/mL, 3.5 mg/mL, and 5 mg/mL collagen Type I rat tail hydrogels were determined experimentally by tracking the pressure drop across the gels as water flowed through the samples, which simultaneously compressed them under pressure. The Holmes-Mow model was used to fit the permeability as the gels underwent compression. A finite element model was created using FEBio to estimate the Young's modulus of collagen gels at the macroscopic level by fitting the experimental pressure vs. the compressive stretch ratio to the model. Our results suggest that the initial permeability of collagen gels decreased with increasing concentration, as expected. However, gels with a lower initial concentration compressed to a greater degree, resulting in smaller final permeabilities once fully compressed. Taken together, our work suggests that the treatment of a collagen gel as an isotropic, elastic material is sufficient to model its transport properties on a macroscopic level but is inadequate if more localized transport properties, which are dependent on network architecture (such as collagen alignment or inhomogeneous densification), are required.

  View details for DOI 10.1016/j.jmbbm.2022.105107

  View details for Web of Science ID 000784290900001

  View details for PubMedID 35182914

• Experimental and Mouse-Specific Computational Models of the <i>Fbln4</i><SUP>SMKO</SUP> Mouse to Identify Potential Biomarkers for Ascending Thoracic Aortic Aneurysm CARDIOVASCULAR ENGINEERING AND TECHNOLOGY Bazzi, M. S., Balouchzadeh, R., Pavey, S. N., Quirk, J. D., Yanagisawa, H., Vedula, V., Wagenseil, J. E., Barocas, V. H. 2022; 13 (4): 558-572

  Abstract

  To use computational methods to explore geometric, mechanical, and fluidic biomarkers that could correlate with mouse lifespan in the Fbln4SMKO mouse. Mouse lifespan was used as a surrogate for risk of a severe cardiovascular event in cases of ascending thoracic aortic aneurysm.Image-based, mouse-specific fluid-structure-interaction models were developed for Fbln4SMKO mice (n = 10) at ages two and six months. The results of the simulations were used to quantify potential biofluidic biomarkers, complementing the geometrical biomarkers obtained directly from the images.Comparing the different geometrical and biofluidic biomarkers to the mouse lifespan, it was found that mean oscillatory shear index (OSImin) and minimum time-averaged wall shear stress (TAWSSmin) at six months showed the largest correlation with lifespan (r2 = 0.70, 0.56), with both correlations being positive (i.e., mice with high OSImean and high TAWSSmin tended to live longer). When change between two and six months was considered, the change in TAWSSmin showed a much stronger correlation than OSImean (r2 = 0.75 vs. 0.24), and the correlation was negative (i.e., mice with increasing TAWSSmin over this period tended to live less long).The results highlight potential biomarkers of ATAA outcomes that can be obtained through noninvasive imaging and computational simulations, and they illustrate the potential synergy between small-animal and computational models.

  View details for DOI 10.1007/s13239-021-00600-4

  View details for Web of Science ID 000745383500001

  View details for PubMedID 35064559

  View details for PubMedCentralID PMC9304450

• An Experimental-Computational Approach to Quantify Blood Rheology in Sickle Cell Disease BIOPHYSICAL JOURNAL Bazzi, M. S., Valdez, J. M., Barocas, V. H., Wood, D. K. 2020; 119 (11): 2307-2315

  Abstract

  In sickle cell disease, aberrant blood flow due to oxygen-dependent changes in red cell biomechanics is a key driver of pathology. Most studies to date have focused on the potential role of altered red cell deformability and blood rheology in precipitating vaso-occlusive crises. Numerous studies, however, have shown that sickle blood flow is affected even at high oxygen tensions, suggesting a potentially systemic role for altered blood flow in driving pathologies, including endothelial dysfunction, ischemia, and stroke. In this study, we applied a combined experimental-computation approach that leveraged an experimental platform that quantifies sickle blood velocity fields under a range of oxygen tensions and shear rates. We computationally fitted a continuum model to our experimental data to generate physics-based parameters that capture patient-specific rheological alterations. Our results suggest that sickle blood flow is altered systemically, from the arterial to the venous circulation. We also demonstrated the application of this approach as a tool to design patient-specific transfusion regimens. Finally, we demonstrated that patient-specific rheological parameters can be combined with patient-derived vascular models to identify patients who are at higher risk for cerebrovascular complications such as aneurysm and stroke. Overall, this study highlights that sickle blood flow is altered systemically, which can drive numerous pathologies, and this study demonstrates the potential utility of an experimentally parameterized continuum model as a predictive tool for patient-specific care.

  View details for DOI 10.1016/j.bpj.2020.10.011

  View details for Web of Science ID 000595631900016

  View details for PubMedID 33096079

  View details for PubMedCentralID PMC7732763

• Effect of viscoelasticity on liquid sheet rupture JOURNAL OF NON-NEWTONIAN FLUID MECHANICS Bazzi, M. S., Carvalho, M. S. 2019; 264: 107-116

  View details for DOI 10.1016/j.jnnfm.2018.10.007

  View details for Web of Science ID 000459364600009