Nitric oxide plays a central role in controlling arterial thrombosis and in cardiovascular diseases by inhibiting the platelet aggregation process. This process is regulated by giving a deactivating signal for the protein membrane integrins, the major platelet adhesion receptors. The localized production of NO, naturally occurring in arterial vessels, is carried out by the NO synthase enzymatic system. Inhibition of platelets aggregation in the coagulation cascade process is due to the antagonist action of NO toward integrin-fibrinogen induced platelet adhesion. However, sometimes the natural supply of NO is not sufficient to prevent clotting. The design of devices for suitable transport and delivery of NO is therefore important. We are developing a new concept of drug delivery in which NO release can be performed by means of polymer shelled microbubbles. The NO release can theoretically be concentrated in vessels with acute thrombosis by bursting of the microparticles upon insonification. This feature is linked to the structural and mechanical properties of the particles shell and it would make minimally invasive local theraphy of acute vascular disease feasible. In this paper, we present a study on some new structural and mechanical features of this microdevice supporting its NO loading capacity and in vitro efficacy in preventing the formation of a clot by releasing NO.

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.

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.

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.