Cellular uptake of rose bengal is mediated by OATP1B1/1B3 transporters.

Due to its fluorescent properties and high yield of singlet oxygen, rose bengal (RB) is one of the most promising photosensitizers for cancer treatment. However, the negative charge of RB molecule may significantly hamper its intracellular delivery by passive diffusion through the cell membrane. Thus, specific membrane protein transporters may be needed. The organic anion transporting polypeptides (OATPs) are a well-characterized group of membrane protein transporters, responsible for cellular uptake of a number of drugs. To our knowledge, this is the first study that evaluates cellular transport of RB mediated by the OATP transporter family. First, electrified liquid-liquid interface, together with biophysical analysis and molecular dynamics simulations were used to characterize the interaction of RB with several models of a cellular membranes. These experiments proved that RB interacts only with the membrane's surface, without spontaneously crossing the lipid bilayer. Evaluation of intracellular uptake of RB by flow cytometry and confocal microscopy showed significant differences in uptake between liver and intestinal cell line models differing in expression of OATP transporters. The use of specific pharmacological inhibitors of OATPs, together with Western blotting and in silico analysis, indicated that OATPs are crucial for cellular uptake of RB.

A survey of methods for the evaluation of tissue engineering scaffold permeability.

The performance of porous scaffolds for tissue engineering (TE) applications is evaluated, in general, in terms of porosity, pore size and distribution, and pore tortuosity. These descriptors are often confounding when they are applied to characterize transport phenomena within porous scaffolds. On the contrary, permeability is a more effective parameter in (1) estimating mass and species transport through the scaffold and (2) describing its topological features, thus allowing a better evaluation of the overall scaffold performance. However, the evaluation of TE scaffold permeability suffers of a lack of uniformity and standards in measurement and testing procedures which makes the comparison of results obtained in different laboratories unfeasible. In this review paper we summarize the most important features influencing TE scaffold permeability, linking them to the theoretical background. An overview of methods applied for TE scaffold permeability evaluation is given, presenting experimental test benches and computational methods applied (1) to integrate experimental measurements and (2) to support the TE scaffold design process. Both experimental and computational limitations in the permeability evaluation process are also discussed.

On the use of in vivo measured flow rates as boundary conditions for image-based hemodynamic models of the human aorta: implications for indicators of abnormal flow.

The purpose of this study is to investigate how the imposition of personalized, non-invasively measured blood flow rates as boundary conditions (BCs) influences image-based computational hemodynamic studies in the human aorta. We extracted from 4D phase-contrast MRI acquisitions of a healthy human (1) the geometry of the thoracic aorta with supra-aortic arteries and (2) flow rate waveforms at all boundaries. Flow simulations were carried out, and the implications that the imposition of different BC schemes based on the measured flow rates have on wall shear stress (WSS)-based indicators of abnormal flow were analyzed. Our results show that both the flow rate repartition among the multiple outlets of the aorta and the distribution and magnitude of the WSS-based indicators are strongly influenced by the adopted BC strategy. Keeping as reference hemodynamic model the one where the applied BC scheme allowed to obtain a satisfactory agreement between the computed and the measured flow rate waveforms, differences in WSS-based indicators up to 49% were observed when the other BC strategies were applied. In conclusion, we demonstrate that in subject-specific computational hemodynamics models of the human aorta the imposition of BC settings based on non-invasively measured flow rate waveforms influences indicators of abnormal flow to a large extent. Hence, a BCs set-up assuring realistic, subject-specific instantaneous flow rate distribution must be applied when BCs such as flow rates are prescribed.