Bioinspired microstructures of chitosan hydrogel provide enhanced wear protection

We describe the fabrication of physical chitosan hydrogels exhibiting a layered structure. This bilayered structure, as shown by SEM and confocal microscopy, is composed of a thin dense superficial zone (SZ), covering a deeper zone (DZ) containing microchannels orientated perpendicularly to the SZ. We show that such structure favors diffusion of macromolecules within the hydrogel matrix up to a critical pressure, σc, above which channels were constricted. Moreover, we found that the SZ provided a higher wear resistance than the DZ which was severely damaged at a pressure equal to the elastic modulus of the gel. The coefficient of friction (CoF) of the SZ remained independent of the applied load with μSZ = 0.38 ± 0.02, while CoF measured at DZ exhibited two regimes: an initial CoF close to the value found on the SZ, and a CoF that decreased to μDZ = 0.18 ± 0.01 at pressures higher than the critical pressure σc. Overall, our results show that internal structuring is a promising avenue in controlling and improving the wear resistance of soft materials such as hydrogels

Effect of polymer architecture on Curcumin 1 encapsulation and release from PEGylated polymer nanoparticles: toward a drug delivery nano-platform to the CNS

We developed a nanoparticles (NPs) library from poly(ethylene glycol)–poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a “micelle-like” or “polymer nano-aggregate” structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to “polymer nano-aggregate” particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers

Unraveling the correlations between conformation, lubrication, and chemical stability of bottlebrush polymers at interfaces

In the present study, we monitored the conformation and chemical stability of a hydrophilic bottlebrush (BB) polymer in pure water and buffered saline solutions. We correlated these parameters to lubricating and wear protecting properties. Using the Surface Forces Apparatus (SFA), we show that the BB polymer partially adsorbs on mica surfaces and extends half its contour length toward the aqueous media. This conformation gives rise to a strong repulsive interaction force when surfaces bearing BB polymer chains are pressed against each other. Analysis of these repulsive forces demonstrated that the adsorbed polymer chains could be described as end-attached elastic rods. After 2 months of aging at temperatures ranging from 4 to 37 °C, partial scission of the BB polymer's lateral chains was observed by Gel Permeation Chromatography with a half-life time of the polymer of at least two years. The thickness of the BB polymer layer assessed by SFA appeared to quickly decrease with aging time and temperature which was mainly caused by the adsorption to the substrate of the released lateral chains. The gradual loss of the BB polymer lateral chains did not impact significantly the tribological properties of the BB polymer solution nor its wear protection capacity. The friction coefficient between mica surfaces immersed in the BB polymer solution was = 0.031 ± 0.002, and was independent of the aging conditions and remained constant up to an applied pressure P = 15 atm. Altogether, this study demonstrates that besides the gradual loss of lateral chains, the BB polymer is still able to perform adequately as a lubricant and wear protecting agent over a time period suitable for in vivo administration

Interaction forces between pegylated star-shaped polymers at mica surfaces

We present a study focused on characterizing the interaction forces between mica surfaces across solutions containing star-shaped polymers with cationic ends. Using the Surface Forces Apparatus, we show that the interaction forces in pure water between surfaces covered with the polymer can be adequately described by the dendronized brush model. In that framework, our experimental data suggest that the number of branches adsorbed at the surface decreases as the concentration of polymer in the adsorbing solution increases. The onset of interaction was also shown to increase with the concentration of polymer in solution up to distances much larger that the contour length of the polymer suggesting that the nanostructure of the polymer film is significantly different from a monolayer. High compression of the polymer film adsorbed at low polymer concentration revealed the appearance of a highly structured hydration layer underneath the polymer layer. The results support that charged polymer chains do not necessarily come into close contact with the surface even if strong electrostatic interaction is present. Altogether, our results provide a comprehensive understanding of the interfacial behavior of star-shaped polymers and revealed the unexpected role of hydration water in the control of the polymer conformation

Lubrication and wear protection of micro-structured hydrogels using bioinspired fluids

We report the fabrication and the use of a bioinspired synovial fluid acting as a lubricant fluid and anti-wear agent at soft and porous chitosan hydrogel tribopairs. This synthetic synovial fluid is composed of sodium hyaluronate (HA) and a bottle-brush polymer (BB) having a polycationic attachment group and polyzwitterionic pendant chains. 2.5 %w/w chitosan hydrogel plugs are organized in a bilayered structure exposing a thin and dense superficial zone (SZ), covering a porous deep zone (DZ) and exhibiting microchannels perpendicularly aligned to the SZ. Using a low-load tribometer, the addition of HA lubricating solution at the hydrogel-hydrogel rubbing contact drastically decreased the coefficient of friction (CoF) from μ = 0.20 ± 0.01 to μ = 0.04 ± 0.01 on the DZ configuration and from μ = 0.31 ± 0.01 to μ = 0.08 ± 0.01 on the SZ surface when increasing HA concentration from 0 to 1000 μg/mL and its molecular mass from 10 to 1500 kDa, similar to what was found when using BB polymer alone. When combining the BB polymer and the 1500 kDa HA, the CoF remained stable at μ = 0.04 ± 0.01 for both studied contact configurations, highlighting the synergistic interaction of the two macromolecules. Hydrogel wear was characterized by assessing the final gel surface roughness by the means of an interferometer. Increasing HA concentration and molecular weight plus the addition of BB polymer lead to a dramatic surface wear protection with a final gel surface roughness of the hydrogels similar to the untested gels. In brief, BB polymer in combination with high molecular weight HA is a potential lubricating fluid as well as a wear resistant agent for soft materials lubrication and wear protection

Wear protection without surface modification using a synergistic mixture of molecular brushes and linear polymers

We describe the design of lubricating and wear protecting fluids based on mixtures of bottlebrushes (BB) and linear polymers solutions. To illustrate this concept we used hyaluronic acid (HA) - a naturally occurring linear polyelectrolyte, and a water soluble synthetic BB polymer. Individually, these two polymers exhibit poor wear protecting capabilities compared to saline solutions. Mixture of the two polymers in pure water or in saline allows to drastically increase wear protection of surfaces over a wide range of shearing conditions. We demonstrate that this synergy between the BB and HA polymers emerges from a strong cohesion between the two components forming the boundary film due to entanglements between both polymers. We show that this concept can be applied to other types of linear polymers and surfaces and is independent of the chemical and mechanical properties of the surfaces

Intermolecular interactions between Bottlebrush Polymers boost the protection of surfaces against frictional wear

"This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemistry of materials, copyright American Chemical Society after peer review and technical editing by the publisher."Polymers exhibiting the bottlebrush (BB) architecture have excellent lubricating properties. However, to motivate their use in real life systems, they must also protect surfaces against frictional damage. In this article, we synthesized a library of polyzwiterrionic bottlebrush polymers of different architectures to explore the effect of intermolecular interactions on their conformation at interfaces and their tribological properties. Using the surface forces apparatus, we show that increasing the number of adhesive blocks on the BB polymers does not impact the friction coefficient on mica surfaces, μ, which remained close to μ = 0.02 but drastically increased the threshold pressure, P*, at which wear initiates from P* = 0.4 ± 0.1 up to 8.0 ± 0.8 MPa. In mixtures of high molecular weight hyaluronic acid and BB polymers, a synergistic interaction between polymers occurred, leading to a significant increase in P*, independently of the BB polymer tested and even reaching superprotection for strongly interacting polymers (up to P* > 14 MPa). Overall, these results show that strong intermolecular interaction between BB polymers and high molecular weight linear polymers is a promising strategy to create highly protective lubricants

Chitosan hydrogel micro-bio-devices with complex capillary patterns via reactive-diffusive self-assembly

International audienceWe present chitosan hydrogel microfluidic devices with self-assembled complex microcapillary patterns, conveniently formed by a diffusion-reaction process. These patterns in chitosan hydrogels are formed by a single-step procedure involving diffusion of a gelation agent into the polymer solution inside a microfluidic channel. By changing the channel geometry, it is demonstrated how to control capillary length, trajectory and branching. Diffusion of nanoparticles (NPs) in the capillary network is used as a model to effectively mimic the transport of nano-objects in vascularized tissues. Gold NPs diffusion is measured locally in the hydrogel chips, and during their two-step transport through the capillaries to the gel matrix and eventually to embedded cell clusters in the gel. In addition, the quantitative analyses reported in this study provide novel opportunities for theoretical investigation of capillary formation and propagation during diffusive gelation of biopolymers.Statement of SignificanceHydrogel micropatterning is a challenging task, which is of interest in several biomedical applications. Creating the patterns through self assembly is highly beneficial, because of the accessible and practical preparation procedure. In this study, we introduced complex self-assembled capillary patterns in chitosan hydrogels using a microfluidic approach. To demonstrate the potential application of these capillary patterns, a vascularized hydrogel with microwells occupied by cells was produced, and the diffusion of gold nanoparticles travelling in the capillaries and diffusing in the gel were evaluated. This model mimics a simplified biological tissue, where nanomedicine has to travel through the vasculature, extravasate into and diffuse through the extracellular matrix and eventually reach targeted cells

Development of bioinspired synthetic synovial fluids

La bioinspiration consiste à analyser les systèmes naturels qui se sont adaptés parfaitement à leurs environnements pour développer des solutions ingénieuses. Ce projet de thèse aborde la thématique de la lubrification articulaire dans le but de développer un traitement contre l'ostéoarthrite (OA). Nous nous sommes inspirés des articulations synoviales, systèmes tribologiques très performants grâce aux interactions synergiques entre la structure unique du cartilage et les molécules lubrifiantes (ML) du fluide synovial (SF). Cependant, lors de l'OA des mécanismes inflammatoires et d'érosion mécanique aboutissent à la dégénérescence progressive du cartilage et la dégradation spécifique des ML du SF (aggrécane et lubricine). Des mimes des ML du SF ont été synthétisés reprenant leur structure particulière dite en écouvillon moléculaire (BB), structure responsable de la lubrification. Des tests tribologiques (SFA, tribomètre) ont montré que les BB garantissent à la fois une faible friction et une résistance à l'usure sur des surfaces dures de mica. Ceci est dû à la présence, sur nos EM, de groupements d'ancrage spécifiques assurant l’adsorption sur la surface de mica et à la formation d'enchevêtrements et d’interactions intermoléculaires avec l'acide hyaluronique de haut poids moléculaire, composant essentiel du SF. Des mimes de cartilage à base d'hydrogels de chitosane multicouches ont été également réalisés reprenant les principales propriétés architecturales du cartilage. En combinaison avec nos EM, ces hydrogels, matériaux poroélastiques fragiles, sont capables d’être lubrifiés avec une friction dans la gamme physiologique et une nette amélioration de leur usureBioinspiration consists in the design of materials inspired by biological systems which have developed ingenious solutions to suit their environment. This project deals with bioinspiration for joint lubrication and in particular for the development of treatments for patients suffering from osteoarthritis (OA). To do so, we took our inspiration from joints which are amongst the most efficient aqueous tribological systems. Their unique properties arise from the complex synergistic interactions between cartilage structure and the lubricant macromolecules of the synovial fluid (SF). However, during OA, inflammatory mechanisms as long as mechanical erosion result in the degeneration of cartilage and lubricant macromolecules (aggrecan and lubricin). Polymeric mimes of the SF have been synthesized based on the bottle-brush (BB) architecture of LUB and AGG which is responsible for the joint lubrication. Tribological tests (SFA, tribometer) showed that BB polymers provided mica surfaces with a low friction and a wear protection up to several megapascals, typically in the range of natural joints. This wear protection was essentially due to the incorporation of anchoring groups specific to mica tribopairs on the BB polymers and the intermolecular bridging and entanglements emerging between BB polymers and high molecular weight HA, another main SF component. Cartilage mimes composed of multilayered chitosan hydrogels were designed to mimic the basic features of cartilage. Along with our BB polymers, the hydrogels, which are poroelastic and fragile materials, provided a low friction and a great decrease of wea