Introducing a biomimetic coating for graphene neuroelectronics: towardin-vivoapplications.

Electronic micro and nano-devices are suitable tools to monitor the activity of many individual neurons over mesoscale networks. However the inorganic materials currently used in microelectronics are barely accepted by neural cells and tissues, thus limiting both the sensor lifetime and efficiency. In particular, penetrating intracortical probes face high failure rate because of a wide immune response of cells and tissues. This adverse reaction called gliosis leads to the rejection of the implanted probe after few weeks and prevent long-lasting recordings of cortical neurons. Such acceptance issue impedes the realization of many neuro-rehabilitation projects. To overcome this, graphene and related carbon-based materials have attracted a lot of interest regarding their positive impact on the adhesion and regeneration of neurons, and their ability to provide high-sensitive electronic devices, such as graphene field effect transistor (G-FET). Such devices can also be implemented on numerous suitable substrates including soft substrates to match the mechanical compliance of cells and tissues, improving further the biocompatibility of the implants. Thus, using graphene as a coating and sensing device material could significantly enhance the acceptance of intracortical probes. However, such a thin monolayer of carbon atoms could be teared off during manipulation and insertion within the brain, and could also display degradation over time. In this work, we have investigated the ability to protect graphene with a natural, biocompatible and degradable polymeric film derivated from hyaluronic acid (HA). We demonstrate that HA-based coatings can be deposited over a wide range of substrates, including intracortical probes and graphene FET arrays without altering the underlying device material, its biocompatibility and sensitivity. Moreover, we show that this coating can be monitoredin situby quantifying the number of deposited charges with the G-FET arrays. The reported graphene functionalization offers promising alternatives for improving the acceptance of various neural interfaces.

Sealing hyaluronic acid microgels with oppositely-charged polypeptides: A simple strategy for packaging hydrophilic drugs with on-demand release.

A simple route to deliver on demand hydrosoluble molecules such as peptides, packaged in biocompatible and biodegradable microgels, is presented. Hyaluronic acid hydrogel particles with a controlled structure are prepared using a microfluidic approach. Their porosity and their rigidity can be tuned by changing the crosslinking density. These negatively-charged polyelectrolytes interact strongly with positively-charged linear peptides such as poly-l-lysine (PLL). Their interactions induce microgel deswelling and inhibit microgel enzymatic degradability by hyaluronidase. While small PLL penetrate the whole volume of the microgel, PLL larger than the mesh size of the network remain confined at its periphery. They make a complexed layer with reduced pore size, which insulates the microgel inner core from the outer medium. Consequently, enzymatic degradation of the matrix is fully inhibited and non-affinity hydrophilic species can be trapped in the core. Indeed, negatively-charged or small neutral peptides, without interactions with the network, usually diffuse freely across the network. By simple addition of large PLL, they are packaged in the core and can be released on demand, upon introduction of an enzyme that degrades selectively the capping agent. Single polyelectrolyte layer appears as a simple generic method to coat hydrogel-based materials of various scales for encapsulation and controlled delivery of hydrosoluble molecules.

Lipid Nanoparticles and Their Hydrogel Composites for Drug Delivery: A Review.

Several drug delivery systems already exist for the encapsulation and subsequent release of lipophilic drugs that are well described in the scientific literature. Among these, lipid nanoparticles (LNP) have specifically come up for dermal, transdermal, mucosal, intramuscular and ocular drug administration routes in the last twenty years. However, for some of them (especially dermal, transdermal, mucosal), the LNP aqueous dispersions display unsuitable rheological properties. They therefore need to be processed as semi-solid formulations such as LNP-hydrogel composites to turn into versatile drug delivery systems able to provide precise spatial and temporal control of active ingredient release. In the present review, recent developments in the formulation of lipid nanoparticle-hydrogel composites are highlighted, including examples of successful encapsulation and release of lipophilic drugs through the skin, the eyes and by intramuscular injections. In relation to lipid nanoparticles, a specific emphasis has been put on the LNP key properties and how they influence their inclusion in the hydrogel. Polymer matrices include synthetic polymers such as poly(acrylic acid)-based materials, environment responsive (especially thermo-sensitive) polymers, and innovative polysaccharide-based hydrogels. The composite materials constitute smart, tunable drug delivery systems with a wide range of features, suitable for dermal, transdermal, and intramuscular controlled drug release.

Biomaterial Applications in Cell-Based Therapy in Experimental Stroke.

Stroke is an important health issue corresponding to the second cause of mortality and first cause of severe disability with no effective treatments after the first hours of onset. Regenerative approaches such as cell therapy provide an increase in endogenous brain structural plasticity but they are not enough to promote a complete recovery. Tissue engineering has recently aroused a major interesting development of biomaterials for use into the central nervous system. Many biomaterials have been engineered based on natural compounds, synthetic compounds, or a mix of both with the aim of providing polymers with specific properties. The mechanical properties of biomaterials can be exquisitely regulated forming polymers with different stiffness, modifiable physical state that polymerizes in situ, or small particles encapsulating cells or growth factors. The choice of biomaterial compounds should be adapted for the different applications, structure target, and delay of administration. Biocompatibilities with embedded cells and with the host tissue and biodegradation rate must be considerate. In this paper, we review the different applications of biomaterials combined with cell therapy in ischemic stroke and we explore specific features such as choice of biomaterial compounds and physical and mechanical properties concerning the recent studies in experimental stroke.

Synthesis and biological evaluation of multivalent carbohydrate ligands obtained by click assembly of pseudo-rotaxanes.

Multivalent carbohydrate ligands have been prepared by assembling alpha-cyclodextrin-based pseudo-rotaxanes through "click chemistry". The inclusion complex formed by a lactosyl-alpha-CD conjugate and a decane axle carrying a lactosyl stopper at one extremity and an azido group at the other end was dimerized by bis-propargyl spacers of different lengths to provide oligorotaxanes having adjustable threading ratios. For the first time, saccharidic ligands have been introduced on rotaxanes both as a biological recognition element and as a capping group. The supramolecular species have been isolated and characterized by mass spectrometry as well as by 1D and DOSY NMR experiments. Their ability to inhibit the binding of Arachis hypogaea agglutinin to asialofetuin, assayed by enzyme linked lectin assays (ELLA), was shown to be valency-dependent.

Effect of electrolyte concentration on the dynamic surface tension and dilational viscoelasticity of adsorption layers of chitosan and dodecyl chitosan.

The effect of an external salt (AcONa) on the kinetics of adsorption and structure formation inside the adsorption layers (ALs) of chitosan (Ch) and dodecyl chitosan (C12Ch) as well as on the frequency dependence of the complex dilational elasticity modulus of these layers has been studied. The complex dilational elasticity modulus of adsorption layers of polymers has been measured on the drop tensiometer (Tracker, IT Concept, France) upon applying a small sinusoidal variation of the drop area with a given frequency, omega, in the range from 10(-2) to 0.63 rad/s and recording the variation of the surface pressure. It has been found that, in the absence of the salt, the dilational storage modulus, E'(omega), of ALs of both Ch and C12Ch is lower with regard to the loss modulus, E' '(omega), in the whole range of frequencies used, testifying for the liquidlike rheological behavior of these layers. With an increase of the salt concentration up to CAcONa > 0.1 M, the ALs become solidlike, as shown when E'(omega) > E' '(omega). Consequently, the characteristic frequency, omega c, corresponding to the intercept between the E'(omega) and E' '(omega) curves, gradually varies from omega c > 1 rad/s to omega c < 0.01 rad/s when the salt concentration is increased from zero to CAcONa = 1 M. Hydrophobically modified C12Ch, having long grafted alkyl chains, exhibited a higher sensitivity to the presence of salt than Ch: the former solidifies more readily and at lower salt concentrations than the latter. It has been found that the experimental E'(omega) and E' '(omega) curves exhibit two characteristic relaxation frequencies, omega 01 approximately 1 rad/s and omega 02 approximately 10(-3)-10(-2) rad/s, whose physical meaning and values were related to the structure of the ALs and to the competitive contribution of electrostatic and hydrophobic interactions between amino and nonpolar groups of Ch and C12Ch to the formation of a gel-like network inside the polymeric film at the interface.

Multilayer films based on host-guest interactions between biocompatible polymers.

Multilayer films are formed using host-guest interaction between two derivatized chitosans, one, with beta-cyclodextrin cavities and the other with adamantyl moieties.