Mature red blood cell (RBC) consists of cytoplasm, mainly normal hemoglobin (HbA) within a plasma membrane. In sickle cell disease, abnormal sickle hemoglobin (HbS) molecule polymerizes and forms into rigid fibers at low oxygen tension, which contributes to variation in the biophysical properties of sickle cells from healthy RBCs. This paper presents an electrical equivalent circuit (EEC) model of sickle cell that considers the phase transition of oxy-HbS solution to deoxy-HbS polymers. Briefly, we model the oxy-HbS solution following healthy RBCs using a resistor and deoxy-HbS fibers as a capacitor. To validate the model, electrical impedance measurements of cell suspensions for normal RBCs and sickle cells are performed, using a multi-channel lock in amplifier in the frequency range of 1 kHz to 10 MHz in a customized microfluidic chamber. Quantitative measurements of the classical components of EEC model are extracted using the developed EEC sickle cell model, allowing us to better understand the biophysics of cell sickling event in sickle cell disease.

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Tissue engineering of the blood-brain barrier (BBB) in vitro has been rapidly expanding to address the challenges of mimicking the native structure and function of the BBB. Most of these models utilize 2D conventional microfluidic techniques. However, 3D microvascular models offer the potential to more closely recapitulate the cytoarchitecture and multicellular arrangement of in vivo microvasculature, and also can recreate branching and network topologies of the vascular bed. In this perspective, we discuss current 3D brain microvessel modeling techniques including templating, printing, and self-assembling capillary networks. Furthermore, we address the use of biological matrices and fluid dynamics. Finally, key challenges are identified along with future directions that will improve development of next generation of brain microvasculature models.

More than a billion people are affected by neurological disorders, and few have effective therapeutic options. A key challenge that has prevented promising preclinically proven strategies is the translation gap to the clinic. Humanized tissue engineering models that recreate the brain environment may aid in bridging this translational gap. Here, we showcase the methodology that allows for the practical fabrication of a comprehensive microphysicological system (MPS) of the blood-brain barrier (BBB). Compared to other existing 2D and 3D models of the BBB, this model features relevant cytoarchitecture and multicellular arrangement, with branching and network topologies of the vascular bed. This process utilizes 3D bioprinting with digital light processing to generate a vasculature lumen network surrounded by embedded human astrocytes. The lumens are then cellularized with primary human brain microvascular endothelial cells and pericytes. To initiate mechanotransduction pathways and complete maturation, vascular structures are continuously perfused for 7 days. Constructs are validated for complete endothelialization with viability dyes prior to functional assessments that include barrier integrity (permeability) and immune-endothelial interactions. This MPS has applications for the study of novel therapeutics, toxins, and elucidating mechanisms of pathophysiology.

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