Marisa Bazzi

All Publications

• 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