Scientific publications

Sustainable production of anti-reflective coatings demands environmentally friendly approaches. This paper introduces a novel method of preparing thin films from an aqueous medium using a sol-gel technique. Single-layer anti-reflective coatings, from water-based silica sols, were prepared and characterized. The thicknesses of thin films were found to be between 75 and 135 nm with refractive indexes between 1.23 and 1.41 and porosities between 7 and 53%. The maximum transmissions of manufactured coatings reached from 99.85% to 99.03% in the visible region. The ageing of silica particles in the aqueous medium was studied using TEM. The transparent water-based sol consisted of individual silicon-dioxide nanoparticles with narrow size distribution (15–20 nm). The TEM images showed, that the silica nanoparticles become uniform and distinguishable within two weeks and no aggregation occurs within 46 days. It was found, that the aqueous silica sol is stable and clear for more than 6 months. The aqueous silica films deposited onto large glass surfaces were found to be homogeneous, with excellent adhesion (Cross Hatch Test is 0; ISO 2409 test standard) and hardness equal to 2H. We present a schematic illustration of the adsorption mechanism of non-ionic silicone surfactant and Pluronic surfactant on the silica surface.

Dendritic cells “patrol” the human body to detect pathogens. In their search, dendritic cells perform a random walk by amoeboid migration. The efficiency of pathogen detection depends on the properties of the random walk. It is not known how the dendritic cells control these properties. Here, we quantify dendritic cell migration under well-defined 2-dimensional confinement and in a 3-dimensional collagen matrix through recording their long-term trajectories. We find 2 different migration states: persistent migration, during which the dendritic cells move along curved paths, and diffusive migration, which is characterized by successive sharp turns. These states exhibit differences in the actin distributions. Our theoretical and experimental analyses indicate that this kind of motion can be generated by spontaneous actin polymerization waves that contribute to dendritic cell polarization and migration. The relative distributions of persistent and diffusive migration can be changed by modification of the molecular actin filament nucleation and assembly rates. Thus, dendritic cells can control their migration patterns and adapt to specific environments. Our study offers an additional perspective on how dendritic cells tune their searches for pathogens.

Abstract Tumor cells present profound alterations in their composition, structural organization, and functional properties. A landmark of cancer cells is an overall altered mechanical phenotype, which so far are linked to changes in their cytoskeletal regulation and organization. Evidence exists that the plasma membrane (PM) of cancer cells also shows drastic changes in its composition and organization. However, biomechanical characterization of PM remains limited mainly due to the difficulties encountered to investigate it in a quantitative and label-free manner. Here, the biomechanical properties of PM of a series of MCF10 cell lines, used as a model of breast cancer progression, are investigated. Notably, a strong correlation between the cell PM elasticity and oncogenesis is observed. The altered membrane composition under cancer progression, as emphasized by the PM-associated cholesterol levels, leads to a stiffening of the PM that is uncoupled from the elastic cytoskeletal properties. Conversely, cholesterol depletion of metastatic cells leads to a softening of their PM, restoring biomechanical properties similar to benign cells. As novel therapies based on targeting membrane lipids in cancer cells represent a promising approach in the field of anticancer drug development, this method contributes to deciphering the functional link between PM lipid content and disease.

Abstract Optogenetics and photonic technologies are changing the future of medicine. To implement light-based therapies in the clinic, patient-friendly devices that can deliver light inside the body while offering tunable properties and compatibility with soft tissues are needed. Here extrusion printing of degradable, hydrogel-based optical waveguides with optical losses as low as 0.1 dB cm−1 at visible wavelengths is described. Core-only and core-cladding fibers are printed at room temperature from polyethylene glycol (PEG)-based and PEG/Pluronic precursors, and cured by in situ photopolymerization. The obtained waveguides are flexible, with mechanical properties tunable within a tissue-compatible range. Degradation times are also tunable by adjusting the molar mass of the diacrylate gel precursors, which are synthesized by linking PEG diacrylate (PEGDA) with varying proportions of DL-dithiothreitol (DTT). The printed waveguides are used to activate photochemical and optogenetic processes in close-to-physiological environments. Light-triggered migration of cells in a photoresponsive 3D hydrogel and drug release from an optogenetically-engineered living material by delivering light across >5 cm of muscle tissue are demonstrated. These results quantify the in vitro performance, and reflect the potential of the printed degradable fibers for in vivo and clinical applications.

Fabrication of intricate and long-term stable 3D polymeric scaffolds by 3D printing technique is still a challenge. The currently used polymeric materials need long post-printing processes and washing steps. In addition, highly concentrated solutions are necessary for maintaining shape fidelity after 3D deposition. This paper reports the fabrication of dual crosslinked 3D scaffolds using a low concentrated (<10 wt-%) ink of Gelatin Methacryloyl (GelMA)/Chitosan and a novel crosslinking agent, a glycerylphytate (G1Phy) to overcome the current limitations in the 3D printing field using hydrogels. The applied methodology consisted of a first ultraviolet light (UV) photopolymerization followed by a post-printing ionic crosslinking treatment with G1Phy. This crosslinker provides a robust framework and avoids the necessity of neutralization with strong bases. The blend ink showed shear-thinning behavior and excellent printability in the form of straight and homogeneous filament. UV curing was undertaken simultaneously to 3D deposition, which enhanced precision, shape fidelity (resolution ≈ 150 µm), and prevented from collapse of the subsequent printed layers (up to 28 layers). In the second step, the novel G1Phy ionic crosslinker agent provided swelling and long term stability properties to the 3D scaffolds. The multi-layered printed scaffolds were mechanically stable at physiological conditions for at least one month. Preliminary in vitro assays using L929 Fibroblasts showed very promising results in terms of adhesion, spreading, and proliferation in comparison to other phosphate-based traditional crosslinkers (i.e. TPP). We envision that the proposed combination of the blend ink and 3D printing approach can have widespread applications in the regeneration of soft tissues.

Mesenchymal stem cells isolated from the Wharton’s jelly of human umbilical cords (WJ-MSC) are of increasing interest for cell therapies, but scalable cell production in stirred tank bioreactors (STR) still requires further investigations in order to be more efficient and with decreased costs. To handle the problem of cell confluence on microcarriers leading to cell aggregation, a new strategy of microcarriers addition was proposed. The ’bead-to-bead transfer’ ability of WJ-MSC was indeed used to maintain constant the number of cells per microcarriers. However, the resulting increase of bead shocks frequency could also negatively impact cell quantity and quality. Until now, no quantitative study describing the impact of bead interactions on WJ-MSC death was reported. In this study the influence of microcarriers addition as well as mixing characteristics on cell viability were determined. Obtained results showed that, when particle mixing is below the just-suspended state condition (Njs), local increase of particle volume fraction promotes a significant cell death in an agitation mode of orbital stirring. However, an increase in agitation rate at Njs is clearly beneficial to cell viability and growth. These effects were magnified during microcarrier addition due to the increase of mean volume fraction of particles. The present study also demonstrates the critical influence of Njs and particle distributions within the bioreactor on WJ-MSC culture performances.

Hydrogels for wound management and tissue gluing applications have to adhere to tissues for a given time scale and then disappear, either by removal from the skin or by slow degradation for applications inside the body. Advanced wound management materials also envision the encapsulation of therapeutic drugs or cells to support the natural healing process. The design of hydrogels that can fulfill all of these properties with minimal chemical complexity, a stringent condition to favor transfer into a real medical device, is challenging. Herein, we present a hydrogel design with a moderate structural complexity that fulfills a number of relevant properties for wound dressing: it can form in situ and encapsulate cells, it can adhere to tissues, and it can be degraded on demand by light exposure under cytocompatible conditions. The hydrogels are based on starPEG macromers terminated with catechol groups as cross-linking units and contain intercalated photocleavable nitrobenzyl triazole groups. Hydrogels are formed under mild conditions (N-(2-hydroxyethyl)piperazine-N′-ethanesulfonic acid (HEPES) buffer with 9–18 mM sodium periodate as the oxidant) and are compatible with encapsulated cells. Upon light irradiation, the cleavage of the nitrobenzyl group mediates depolymerization, which enables the on-demand release of cells and debonding from tissues. The molecular design and obtained properties reported here are interesting for the development of advanced wound dressings and cell therapies and expand the range of functionality of current alternatives.

Soft robots consisting of stimuli-responsive soft materials are expected to achieve tasks otherwise impossible by robots with conventional rigid counterparts. In spite of good progress made over the past several years, robot mobility on various surfaces remains challenging. Here, we report a footed soft robot with good terrain adaptability and large load carrying capability by mimicking the anisotropic friction of gecko setae and the gait of caterpillars. The robot, termed as Geca-Robot, is composed of gecko-inspired triangular micropillars as the feet and alternating cuboids of polydimethylsiloxane (PDMS) and graphene–PDMS as the muscle. Geca-Robot is remotely powered by light with wavelengths ranging from ultraviolet to infrared, and moves with a caterpillar-like gait. The gecko-inspired feet allows Geca-Robot to unidirectionally travel on terrains of varying roughness, slope, and dryness with a wide working temperature range, and to carry loads weighing approximately 50 times its own mass. Geca-Robot will inspire the creation of further soft robot designs for various natural terrains.

In this paper we explore the printability of reversible networks formed by catechol functionalized PEG solutions and metal cations (Al3+, Fe3+ or V3+). The printability and shape fidelity were dependent on the ink composition (metal ion type, pH, PEG molecular weight) and printing parameters (extrusion pressure and printing speed). The relaxation time, recovery rate and viscosity of the inks were analyzed in rheology studies and correlated with thermodynamic and ligand exchange kinetic constants of the dynamic bonds and the printing performance (i.e. shape fidelity of the printed structures). The relevance of the relaxation time and ligand exchange kinetics for printability was demonstrated. Cells seeded on the materials crosslinked with Al3+, Fe3+ ions were viable and revealed well-spread morphologies during 7 day culture, indicating the potential of the formulations to be used as inks for cell encapsulation. The proposed dynamic ink design offers significant flexibility for 3D bioprinting, and enables straightforward adjustment of the printable formulation to meet application-specific needs.

Light-responsive hydrogels are useful platforms to study cellular responses. Current photosensitive motifs need UV light to be activated, which is intrinsically cytotoxic and has a low penetration depth in tissues. Herein we describe a strategy for near-infrared (NIR) controlled activation of cellular processes (3D cell spreading and angiogenesis) by embedding upconverting nanoparticles (UCNPs) in a hydrogel modified with light-activatable cell adhesive motifs. The UCNPs can convert NIR light (974 nm) into local UV emission and activate photochemical reactions on-demand. Such optoregulation is spatially controllable, dose-dependent and can be performed at different timepoints of the cell culture without appreciable photodamage of the cells. HUVEC cells embedded in this hydrogel can form vascular networks at predefined geometries determined by the irradiation pattern. The penetration depth of NIR light enabled activation of the angiogenesis response through skin tissue with a thickness of 2.5 mm. Our strategy opens a new avenue for 4D cell cultures, with the potential to be extended to dynamically manipulate cell–matrix interactions and derived cellular processes in vivo.