Designing multivalent probes for tunable superselective targeting

This is the author accepted manuscript. The final version is available from PNAS via http://dx.doi.org/10.1073/pnas.1500622112Specific targeting is common in biology and is a key challenge in nanomedicine. It was recently demonstrated that multivalent probes can selectively target surfaces with a defined density of surface binding sites. Here we show, using a combination of experiments and simulations on multivalent polymers, that such “superselective” binding can be tuned through the design of the multivalent probe, to target a desired density of binding sites. We develop an analytical model that provides simple yet quantitative predictions to tune the polymer’s superselective binding properties by its molecular characteristics such as size, valency, and affinity. This work opens up a route toward the rational design of multivalent probes with defined superselective targeting properties for practical applications, and provides mechanistic insight into the regulation of multivalent interactions in biology. To illustrate this, we show how the superselective targeting of the extracellular matrix polysaccharide hyaluronan to its main cell surface receptor CD44 is controlled by the affinity of individual CD44–hyaluronan interactions.This work was supported by the Marie Curie Career Integration Grant “CELLMULTIVINT,” PCIG09-GA-2011-293803 (to G.V.D.), and the European Research Council (ERC) Starting Grant “JELLY,” 306435 (to R.P.R.). D.F. acknowledges ERC Advanced Grant 227758 and EPSRC Programme Grant EP/I001352/1. T.C. acknowledges support from the Herchel Smith Fund

Rheological properties of calcium carbonate self-setting injectable paste

With the development of minimally invasive surgical techniques, there is growing interest in the research and development of injectable biomaterials with controlled rheological properties. In this context, the rheological properties and injectability characteristics of an original CaCO3 self-setting paste have been investigated. Two complementary rheometrical procedures have been established using a controlled stress rheometer to follow the structure build-up at rest or during gentle mixing and/or handling on the one hand, and the likely shear-induced breakdown of this structure at 25 or 35 C on the other. The data obtained clearly show the influence of temperature on the development of a cement microstructure during setting, in all cases leading to a microporous cement made of an entangled network of aragonite-CaCO3 needle-like crystals. Linear viscoelastic measurements arriving from an oscillatory shear at low deformation showed a progressive increase in the viscous modulus (G0 0) during paste setting, which is enhanced by an increase in temperature. In addition, steady shear measurements revealed the shear-thinning behaviour of this self-setting paste over an extended period after paste preparation and its ability to re-build through progressive paste setting at rest. The shear-thinning behaviour of this self-setting system was confirmed using the injectability system and a procedure we designed. The force needed to extrude a homogeneous and continuous column of paste decreases strongly upon injection and reaches a weight level to apply on the syringe piston around 2.5 kg, revealing the ease of injection of this CaCO3 self-setting paste

Development of an injectable composite for bone regeneration

With the development of minimally invasive surgical techniques, there is a growing interest in the research and development of injectable biomaterials especially for orthopedic applications. In a view to enhance the overall surgery benefits for the patient, the BIOSINJECT project aims at preparing a new generation of mineral-organic composites for bone regeneration exhibiting bioactivity, therapeutic activity and easiness of use to broaden the application domains of the actual bone mineral cements and propose an alternative strategy with regard to their poor resorbability, injectability difficulties and risk of infection. First, a physical-chemical study demonstrated the feasibility of self-setting injectable composites associating calcium carbonate-calcium phosphate cement and polysaccharides (tailor-made or commercial polymer) in the presence or not of an antibacterial agent within the composite formulation. Then, bone cell response and antimicrobial activity of the composite have been evaluated in vitro. Finally, in order to evaluate resorption rate and bone tissue response an animal study has been performed and the histological analysis is still in progress. These multidisciplinary and complementary studies led to promising results in a view of the industrial development of such composite for dental and orthopaedic applications

Self-assembling polysaccharide systems based on cyclodextrin complexation: Synthesis, properties and potential applications in the biomaterials field

International audienc

Novel hyaluronan-based supramolecular assemblies stabilized by multivalent specific interactions: rheological behavior in aqueous solution

International audienceThe behavior in aqueous medium of new hyaluronic acid (HA) based supramolecular assemblies was fully investigated by rheological measurements. The physical networks studied are stabilized by specific interactions between (i) monomeric β-cyclodextrin (CD) and adamantane (AD) molecules or (ii) dimeric CD and AD molecules, each randomly grafted along the polysaccharide chain. The viscoelastic properties of the resulting "mono- and bi-sticker systems", in which inclusion complexes play the role of sticky point, were analyzed as a function of polymer concentration, temperature and addition of host competitive molecules. These networks were shown to exhibit a marked non-Maxwellian behavior. The mono- and bi-interchain complexes considerably slow down the global dynamic and are believed to involve unusual viscoelastic properties that clearly differ from those of alkylated HA-based systems. These rheological features could be explained by a special mechanism of association leading to the formation of networks constituted by double-chain strands connected by fourfold junction points

Hydrogel-Colloid Composite Bioinks for Targeted Tissue-Printing

International audienceThe development of extrusion-based bioprinting for tissue engineering is conditioned by the design of bioinks displaying adequate printability, shape stability, and postprinting bioactivity. In this context, simple bioink formulations, made of cells supported by a polymer matrix, often lack the necessary versatility. To address this issue, intense research work has been focused on introducing colloidal particles into the ink formulation. By creating weak cross-links between polymer chains, added particles modify the rheology and mechanical behavior of bioinks to improve their printability and structural integrity. Additionally, nano- and microscopic particles display composition- and structure-specific properties that can affect the cellular behavior and enhance the formation of tissue within the printed material. This Review offers a comprehensive picture of the role of colloids in bioprinting from a physicochemical and biological perspective. As such, it provides guidance on devising adaptable bioinks for the fabrication of biomimetic tissues