The availability of an autologous transplantable auxiliary liver would dramatically affect the treatment of liver disease. Assembly and function in vivo of a bioengineered human liver derived from induced pluripotent stem cells (iPSCs) has not been previously described. By improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, we generated functional engineered human mini livers and performed transplantation in a rat model. Whereas previous studies recellularized liver scaffolds largely with rodent hepatocytes, we repopulated not only the parenchyma with human iPSC-hepatocytes but also the vascular system with human iPS-endothelial cells, and the bile duct network with human iPSC-biliary epithelial cells. The regenerated human iPSC-derived mini liver containing multiple cell types was tested in vivo and remained functional for 4 days after auxiliary liver transplantation in immunocompromised, engineered (IL2rg À/À ) rats.

BackgroundRight ventricular (RV) diastolic function has been associated with outcomes for patients with pulmonary hypertension; however, the relationship between biomechanics and hemodynamics in the right ventricle has not been studied.Methods and ResultsRat models of RV pressure overload were obtained via pulmonary artery banding (PAB; control, n=7; PAB, n=5). At 3 weeks after banding, RV hemodynamics were measured using a conductance catheter. Biaxial mechanical properties of the RV free wall myocardium were obtained to extrapolate longitudinal and circumferential elastic modulus in low and high strain regions (E1 and E2, respectively). Hemodynamic analysis revealed significantly increased end‐diastolic elastance (Eed) in PAB (control: 55.1 mm Hg/mL [interquartile range: 44.7–85.4 mm Hg/mL]; PAB: 146.6 mm Hg/mL [interquartile range: 105.8–155.0 mm Hg/mL]; P=0.010). Longitudinal E1 was increased in PAB (control: 7.2 kPa [interquartile range: 6.7–18.1 kPa]; PAB: 34.2 kPa [interquartile range: 18.1–44.6 kPa]; P=0.018), whereas there were no significant changes in longitudinal E2 or circumferential E1 and E2. Last, wall stress was calculated from hemodynamic data by modeling the right ventricle as a sphere: )(stress=Pressure×radius2×thickness.Conclusions RV pressure overload in PAB rats resulted in an increase in diastolic myocardial stiffness reflected both hemodynamically, by an increase in Eed, and biomechanically, by an increase in longitudinal E1. Modest increases in tissue biomechanical stiffness are associated with large increases in Eed. Hemodynamic measurements of RV diastolic function can be used to predict biomechanical changes in the myocardium.

In the stomach, a layer of gastric mucus protects the epithelial cells of the stomach wall against damage by the acidic digestive juices in the gastric lumen. Despite considerable research, the biophysical mechanisms for this acid barrier are not understood. We present an in vitro microfluidic tool to characterize the stomach acid barrier, in which purified mucin polymers are "secreted" against an acidic zone on chip, mimicking the in vivo secretion of gastric mucus into an acidic stomach lumen. This device reconstitutes both the H(+) concentration gradient and outward flow environment of the mucus layer in vivo. Our experiments demonstrate that a continuously secreted mucin layer hinders acid diffusion, suggesting novel insights into the barrier role of mucins. More broadly, our system may serve as a platform tool for studying the barrier functions provided by mucus layers in the body and for studying mucus drug interactions.

or alexandra.collin@ pitt.edu. Endothelial cells are prevalent in our bodies and serve multiple functions. By lining the vasculature, they provide a barrier to tissues and facilitate the transport of molecules and cells. They also maintain hemostasis and modulate blood flow by reacting to chemokines and releasing signal molecules. Thus, endothelial dysfunction leads to a wide variety of diseases, including atherosclerosis and coronary artery disease. In today's era of stem cell research, induced pluripotent stem cellederived endothelial cells (iPSC-ECs) have emerged for research and engineering purposes. They are not only tools for studying disease states but are also a crucial part of efforts to engineer vessel and organ grafts. As the techniques in cell culture, microfluidics, and personalized medicine concomitantly improve, the potential for iPSC-ECs is enormous. We review functions of endothelium in our bodies, the development and uses of iPSC-ECs, and the possible avenues to explore in the future.

Biopolymer-based hydrogels such as mucus and the basal lamina play a key role in biology where they control the exchange of material between different compartments. They also pose a barrier that needs to be overcome for successful drug delivery. Characterizing the permeability properties of such hydrogels is mandatory for the development of suitable drug delivery vectors and pharmaceutics. Here, we present an experimental method to measure bulk particle transport through hydrogels. We validate our assay by applying it to mucin hydrogels and show that the permeability properties of these mucin hydrogels can be modulated by the polymer density and pH, in agreement with previous results obtained from single particle tracking. The method we present here is easy to handle, inexpensive, and high-throughput compatible. It is also a suitable platform for the design and screening of drugs that aim at modifying the barrier properties of hydrogels. This system can also aid in the characterization and development of synthetic gels for a wide range of biomedical applications.