Integration of reconstructed human skin (RhS) into organ‐on‐chip (OoC) platforms addresses current limitations imposed by static culturing. This innovation, however, is not without challenges. Microfluidic devices, while powerful, often encounter usability, robustness, and gas bubble issues that hinder large‐scale high‐throughput setups. This study aims to develop a novel re‐usable multi‐well microfluidic adaptor (MMA) with the objective to provide a flexible tool for biologists implementing complex 3D biological models (e.g., skin) while enabling simultaneous user control over temperature, medium flow, oxigen (O₂), nitrogen (N₂), and carbon dioxide (CO₂) without the need for an incubator. The presented MMA device is designed to be compatible with standard, commercially available 6‐well multi‐well plates (6MWPs) and 12‐well transwells. This MMA‐6MWP setup is employed to generate a skin‐on‐chip (SoC). RhS viability is maintained under flow for three days and their morphology closely resembles that of native human skin. A proof‐of‐concept study demonstrates the system's potential in toxicology applications by combining endothelialised RhS with flowing immune cells. This dynamic setting activates the monocyte‐like MUTZ‐3 cells (CD83 and CD86 upregulation) upon topical exposure of RhS to a sensitizer, revealing the MMA‐6MWP's unique capabilities compared to static culturing, where such activation is absent.

Hepatic sinusoids are lined with thin endothelial cells with transcellular pores, termed fenestrations. These fenestrations are open channels that connect the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. Fenestrations range from 0.05 to 0.35 µm in diameter and cover 5–15% of the sinusoidal endothelial surface area, depending on their location along the sinusoids. The direct measurement of hemodynamic parameters, such as pressure and flow velocity, remains challenging within the narrow sinusoids. Such knowledge would increase our understanding of the physiology of the hepatic niche and possible implications in aging or diseases in which fenestrations are reduced or lost. Few simulations of liver blood flow focus on the level of the individual sinusoid, and fewer still include the transcellular pores (fenestrations) of the sinusoidal endothelium. Furthermore, none have included (i) a porosity gradient along the sinusoid wall, modeled using through-all pores rather than a porous medium, (ii) the presence of the SoD, or (iii) lymphatic drainage. Herein, computed fluid dynamics (CFD) simulations were performed using a numerical model with relevant anatomical characteristics (length, diameter, porosity, inlet/outlet pressure, and lymphatic outflow from the portal region of the SoD). The greatest contribution to luminal velocity magnitude and pressure was the overall shape of the vessel. Divergent-radius models yielded velocity magnitudes 1.5–2 times higher than constant-radius models, and pressures were 5–8% lower in the divergent-radius models compared to the constant-radius models. Porosity only modestly contributed to luminal pressure. The luminal velocity magnitude was largely unaffected by the presence or absence of lymphatic drainage. Velocity magnitudes through fenestrations were lower in higher-porosity models (20%) vs. lower-porosity models (5%) across all models (0.4–0.55-fold lower). Velocity magnitudes through the space of Disse were increased 3–4 times via the addition of lymphatic drainage to the models, while pressures were decreased by 6–12%. The flow velocity in the SoD was modified via differences in porosity, while the flow velocity in the lumens of the sinusoids was largely unaffected. The overall shape of the vessel is the single most important factor in the pressure flow behavior of the sinusoidal lumen. The flow rate over hepatocytes and the SoD is modestly affected by the distribution of porosity along the sinusoid and greatly affected by the lymphatic drainage, parameters that would be of interest for modeling the exchange of blood with the hepatic parenchyma.

The hepatic sinusoids are lined by thin endothelium containing transcellular pores dubbed fenestra. These fenestrations are completely open channels connecting the sinusoidal lumen to the underlying Space of Disse (SoD) and the hepatocytes of the liver parenchyma. The fenestrations are in the size range 0.05-0.35µm in diameter and cover between 5-15% of the sinusoidal endothelial surface area depending on their location along the sinusoids. Motivation/Research Question: So far, the narrowness of the sinusoids prevented the direct measurement of hemodynamic features such as sinusoidal pressure and flow velocity. A better understanding of these parameters might help in better understanding the physiology of the hepatic niche and possible implications in liver diseases. Few simulations of liver blood flow focus on the level of the individual sinusoid, fewer still include the transcellular pores (fenestrations) of the sinusoidal endothelium, and none have included i) a porosity gradient along the sinusoid wall modelled with through-all pores rather than a porus medium, ii) the presence of the Space of Disse, iii) lymphatic drainage. Model: Computed fluid dynamic (CFD) simulations performed using a numerical model with relevant anatomical characteristics (length, diameter, porous size and porosity). Boundary conditions included physiological/pathological values of inlet/outlet pressure and lymphatic outflow from the portal region of the SoD. Results: The pressure and flow velocity of the sinusoidal lumen was entirely dependent on the shape, i.e. constant versus divergent radius and not dependent on porosity in the sinusoidal wall. The velocity through the space of Disse (SoD) was affected by the addition of lymphatic drainage and increases in porosity in the pericentral area of the model. Variations in porosity also affected flow velocity through the fenestrations. Conclusions: The flow velocity in the SoD was modified by differences in porosity, while the flow velocity in the lumen of the sinusoids was unaffected, even by the absence of fenestrations. The overall shape of the vessel is the singular most important factor in the pressure flow behavior of the sinusoidal lumen. The flow rate over the hepatocytes is the flow rate through the SoD, and is modestly affected by the distribution of porosity along the sinusoid, and by the addition of a lymphatic drainage, this parameter would be of interest for modelling blood exchange with the hepatic parenchyma, especially if accounting for zonation.