Water dynamics in physical hydrogels based on partially hydrophobized hyaluronic acid.

The dynamics of hyaluronate-based hydrogels has been investigated by quasielastic neutron scattering (QENS). Hyaluronate (HYA) has been compared, in the same conditions of temperature and polymer concentration, to a chemically modified form, HYADD, in which the backbone has been grafted with a hexadecyl (C(16)) side-chain with a degree of substitution of about 2% (mol/mol). This modification increases the hydrophobicity of the polysaccharide and leads to a stable gel already at polymer concentration of 0.3% (w/v), yielding a viscosupplementation with less quantity of polysaccharide. The time-scale covered by our measurements probes both water and segmental biopolymer motions. In both systems, the local dynamics of the network in the ps time-scale is mostly due to local reorientational motions of side groups. Such motions are not significantly affected by the small amount of aliphatic chains forming the hydrophobic junctions in HYADD. The diffusivity of water in both HYA and HYADD coincides with that of pure water within the experimental uncertainty. This result confirms previous ones on the dynamics of water in HYA solutions and it is of relevance for biomedical applications of hyaluronate-based systems because it affects the diffusive processes of metabolites and their interaction with tissues.

A new viscosupplement based on partially hydrophobic hyaluronic acid: a comparative study.

A novel partially hydrophobized derivative of hyaluronic acid (HYADD® 4), containing a low number of C16 side-chains per polysaccharide backbone, provides injectable hydrogels stabilized by side-chain hydrophobic interactions. The rheological properties of Hymovis®, a physical hydrogel based on the hyaluronic acid derivative HYADD® 4, were evaluated using as reference a solution of the parent natural polysaccharide, hyaluronic acid. The rheological measurements were performed both in flow and oscillation regimes at the physiological frequency values of the knee, typically spanning the range from 0.5 Hz (walking frequency) to 3 Hz (running frequency). Moreover, the viscoelastic features of Hymovis® were compared with the market-available viscosupplementation products in view of its use in joint diseases.The different behavior of the investigated materials in crossover frequency measurements and in structure recovery experiments can be explained on the basis of the structural and dynamic properties of the polymeric systems.

Adding chemical cross-links to a physical hydrogel.

Synergistic hydrogels are often encountered in polysaccharide mixtures widely used in food and biopharma products. The xanthan and konjac glucomannan pair provides one of the most studied synergistic hydrogels. Recently we showed that the junction zones stabilizing the 3D structure of this gel are present as macromolecular complexes in solution formed by the partially depolymerised polysaccharidic chains. The non-covalent interactions stabilizing the structure of the polysaccharidic complex cause the melting of the ordered structure of the complex in the solution and of the hydrogels. Introduction of chemical cross-links in the 3D structure of the synergistic hydrogel removes this behaviour, adding new features to the swelling and to the viscoelastic properties of the cured hydrogel. The use of epichlorohydrin as low molecular weight cross-linker does not impact unfavourably on the viability of NIH 3T3 fibroblasts.

Gel-like structure of a hexadecyl derivative of hyaluronic acid for the treatment of osteoarthritis.

Hyaluronic acid is a polysaccharide with viscoelastic and mechanical properties that are crucial for the normal functioning of osteoarticular junctions. It is demonstrated that introduction of a hexadecyl side chain into HA yields an injectable polysaccharide capable of forming physical hydrogels, which are stable at very low polymer concentrations, whereas native hyaluronic acid forms viscous solutions at concentrations that are ten times higher. Characterization of this system showed that the driving force for its gel-like behavior is the occurrence of hydrophobic interactions involving aliphatic side chains, despite the low degree of substitution, as confirmed by molecular dynamics simulations of HYADD4 and HA hydrogels.

Water, solute, and segmental dynamics in polysaccharide hydrogels.

Polysaccharide hydrogels have found several applications in the food industry, in biomedicine, and cosmetics. The study of polysaccharide hydrogels offers a challenging scenario of intrinsic heterogeneities in the crosslinking density and large time and space ranges that characterize a number of dynamic processes entailing segmental motions, water diffusion, and small-molecule diffusion. The understanding of such complex features is essential because of the extensive use of polysaccharidic moieties in the food industry, biomedical devices, and cosmetics. The study of phenomena occurring at the nanoscale to the mesoscale requires the combination of investigative tools to probe different time and distance scales and the structural characterization of the networks by established methodologies such as swelling and elastic modulus measurements. Elastic and quasielastic neutron scattering, and fluorescence recovery after photobleaching are emerging methodologies in this field. In this feature article we focus, somewhat arbitrarily, on these new approaches because other techniques, such as low-resolution proton NMR relaxometry and rheology, have been already described thoroughly in the literature. Case examples of polysaccharide hydrogels studied by neutron scattering and fluorescence recovery are presented here as contributions to the comprehension of the dynamic behavior of physical and chemical hydrogels based on polysaccharides. Quasielastic incoherent neutron scattering experiment on a Sephadex hydrogel sample at different temperatures.