Publications

Many neurodegenerative diseases are identified but their causes and cure are far from being well-known. The problem resides in the complexity of the neural tissue and its location which hinders its easy evaluation. Although necessary in the drug discovery process, in vivo animal models need to be reduced and show relevant differences with the human tissues that guide scientists to inquire about other possible options which lead to in vitro models being explored. From organoids to organ-on-a-chips, 3D models are considered the cutting-edge technology in cell culture. Cell choice is a big parameter to take into consideration when planning an in vitro model and cells capable of mimicking both healthy and diseased tissue, such as induced pluripotent stem cells (iPSC), are recognized as good candidates. Hence, we present a critical review of the latest models used to study neurodegenerative disease, how these models have evolved introducing microfluidics platforms, 3D cell cultures, and the use of induced pluripotent cells to better mimic the neural tissue environment in pathological conditions.

JTD Keywords: 3d in vitro models, bioprinting, ipsc cell culture, microfluidic device, 3d in vitro models, Bioprinting, Blood-brain-barrier, Cerebral organoids, Culture model, Endothelial-cells, Expression profile, Extracellular-matrix, Ipsc cell culture, Microfluidic device, Neurodegenerative diseases, On-a-chip, Pluripotent stem-cells, Shear-stress, Substrate stiffness

Endothelial coverage of an exposed cardiovascular stent surface leads to the occurrence of restenosis and late-stent thrombosis several months after implantation. To overcome this difficulty, modification of stent surfaces with topographical or biochemical features may be performed to increase endothelial cells’ (ECs) adhesion and/or migration. This work combines both strategies on cobalt-chromium (CoCr) alloy and studies the potential synergistic effect of linear patterned surfaces that are obtained by direct laser interference patterning (DLIP), coupled with the use of Arg-Gly-Asp (RGD) and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptides. An extensive characterization of the modified surfaces was performed by using AFM, XPS, surface charge, electrochemical analysis and fluorescent methods. The biological response was studied in terms of EC adhesion, migration and proliferation assays. CoCr surfaces were successfully patterned with a periodicity of 10 µm and two different depths, D (≈79 and 762 nm). RGD and YIGSR were immobilized on the surfaces by CPTES silanization. Early EC adhesion was increased on the peptide-functionalized surfaces, especially for YIGSR compared to RGD. High-depth patterns generated 80% of ECs’ alignment within the topographical lines and enhanced EC migration. It is noteworthy that the combined use of the two strategies synergistically accelerated the ECs’ migration and proliferation, proving the potential of this strategy to enhance stent endothelialization.

JTD Keywords: adhesion, bare-metal, biofunctionalization, biomaterials, cell adhesive peptides, cobalt-chromium alloy, direct laser interference patterning (dlip), endothelial cell migration, functionalization, matrix, proliferation, selectivity, shear-stress, surfaces, Direct laser interference patterning (dlip), Drug-eluting stents, Endothelial cell migration

Microphysiological systems (MPS) or organs-on-chips (OoC) can emulate the physiological functions of organs in vitro and are effective tools for determining human drug responses in preclinical studies. However, the analysis of MPS has relied heavily on optical tools, resulting in difficulties in real-time and high spatial resolution imaging of the target cell functions. In this study, the role of scanning probe microscopy (SPM) as an analytical tool for MPS is evaluated. An access hole is made in a typical MPS system with stacked microchannels to insert SPM probes into the system. For the first study, a simple vascular model composed of only endothelial cells is prepared for SPM analysis. Changes in permeability and local chemical flux are quantitatively evaluated during the construction of the vascular system. The morphological changes in the endothelial cells after flow stimulation are imaged at the single-cell level for topographical analysis. Finally, the possibility of adapting the permeability and topographical analysis using SPM for the intestinal vascular system is further evaluated. It is believed that this study will pave the way for an in situ permeability assay and structural analysis of MPS using SPM.

JTD Keywords: cell, electrochemical microscopy, membrane-permeability, microphysiological systems, organs-chips, platform, scanning electrochemical microscopy, scanning ion conductance microscopy, scanning probe microscopy, shear-stress, surface-topography, Ion conductance microscopy, Microphysiological systems, Organs-chips, Scanning electrochemical microscopy, Scanning ion conductance microscopy, Scanning probe microscopy

© 2020 American Chemical Society. The performance of supramolecular nanocarriers as drug delivery systems depends on their stability in the complex and dynamic biological media. After administration, nanocarriers are challenged by physiological barriers such as shear stress and proteins present in blood, endothelial wall, extracellular matrix, and eventually cancer cell membrane. While early disassembly will result in a premature drug release, extreme stability of the nanocarriers can lead to poor drug release and low efficiency. Therefore, comprehensive understanding of the stability and assembly state of supramolecular carriers in each stage of delivery is the key factor for the rational design of these systems. One of the main challenges is that current 2D in vitro models do not provide exhaustive information, as they fail to recapitulate the 3D tumor microenvironment. This deficiency in the 2D model complexity is the main reason for the differences observed in vivo when testing the performance of supramolecular nanocarriers. Herein, we present a real-time monitoring study of self-assembled micelles stability and extravasation, combining spectral confocal microscopy and a microfluidic cancer-on-a-chip. The combination of advanced imaging and a reliable 3D model allows tracking of micelle disassembly by following the spectral properties of the amphiphiles in space and time during the crucial steps of drug delivery. The spectrally active micelles were introduced under flow and their position and conformation continuously followed by spectral imaging during the crossing of barriers, revealing the interplay between carrier structure, micellar stability, and extravasation. Integrating the ability of the micelles to change their fluorescent properties when disassembled, spectral confocal imaging and 3D microfluidic tumor blood vessel-on-a-chip resulted in the establishment of a robust testing platform suitable for real-time imaging and evaluation of supramolecular drug delivery carrier's stability.

JTD Keywords: cancer-on-a-chip, complex, delivery, endothelial-cells, in-vitro, microfluidic, model, nanoparticle, penetration, shear-stress, stability, supramolecular, Cancer-on-a-chip, Cell-culture, Micelle, Microfluidic, Nanoparticle, Stability, Supramolecular