Hyaluronic acid single-network hydrogel with high stretchable and elastic properties.

Stretchable materials have demonstrated great interest in wearable or implantable applications. Most of the existing hydrogels with high stretchability characteristics are based on double networks, exhibit large hysteresis loops, and cannot recover after deformation due to permanent rupture of network. Elastic, biodegradable, and biocompatible hydrogels are desirable for wound dressing of joints with frequent motions or post-surgical healing of mobile tissues. Here, we show a simple strategy for the preparation of a hyaluronic acid (HA) single-network hydrogel that can be stretchable and highly elastic without the addition of other components/partners or complicated processes of preparation. Our strategy relies on the use of high Mw HA to create a chemical hydrogel in which densely entangled HA chains are tied together by a small number of covalent bonds. While the presence of covalent cross-links can prevent disintegration of the HA network, entanglements endow the hydrogel with high stretchability through transmission of tension along the length of the long HA chains. The stretching-relaxation cycles show negligible hysteresis and perfect recovery of material after the release of force. The diminution of Mw together with increasing the concentration or cross-linker amount leads to brittle hydrogels.

Polysaccharide-blend multilayers containing hyaluronan and heparin as a delivery system for rhBMP-2.

It is shown that blend multilayers of hyaluronan (HA) and heparin (HEP) as polyanions and poly(L-lysine) (PLL) as a polycation can be used to prepare films with different thicknesses and chemical compositions. The amounts of recombinant human BMP-2 (rhBMP-2) loaded and the fraction initially released from the films depend on the film's chemical composition. The amounts of rhBMP-2 loaded in the films are much higher for HA mass fractions of more than 0.4. The bioactivity of the rhBMP-2-loaded films is investigated on C2C12 myoblasts, which differentiates into osteoblasts in contact with the films. The alkaline phosphatase expression for cells grown on nanoblend films of various compositions falls over a unique curve. This suggests that the cells "sensing" the rhBMP-2 are not influenced by the film's chemistry. The rhBMP-2 can sustain at least three successive culture sequences while remaining bioactive, thus confirming the important and protective effect of rhBMP-2. Altogether, these results indicate that crosslinked PLL/HA films have superior properties for the incorporation of rhBMP-2 and on its long-lasting bioactivity.

Designing hyaluronic acid-based layer-by-layer capsules as a carrier for intracellular drug delivery.

Polyelectrolyte microcapsules were prepared by the layer-by-layer assembly of hyaluronic acid (HA) and a polycationic polymer, poly(allylamine) (PAH) or poly(lysine) (PLL). The influence of the polycationic partner on the morphology, stability, permeability properties, and enzymatic degradation of microcapsules was thoroughly analyzed. It was found that these properties could be tuned by shell cross-linking. Confocal microscopy studies of cellular uptake of the capsules showed that the polyelectrolyte shells remain stable outside the cells but readily break open once internalized by cells, suggesting their potential as carrier for intracellular drug delivery.

Multilayer assembly of hyaluronic acid/poly(allylamine): control of the buildup for the production of hollow capsules.

The objective of this work was to investigate the formation of hollow microcapsules composed of hyaluronic acid (HA) and poly(allylamine) (PAH) by layer-by-layer adsorption on CaCO 3 microparticles and subsequent core removal by addition of chelating agents for calcium ions. We found that the molecular weight of HA as well as the HA solution concentration used during deposition are crucial parameters influencing the multilayer structure. Whereas the effect of molecular weight of HA was mainly attributed to the porous structure of the template which allows penetration of polyelectrolytes when their size is below the maximum pore size of the template ( approximately 60 nm), that of the concentration of the HA solution was related to the intrinsic properties of the polysaccharide. Indeed, as shown by quartz crystal microbalance with dissipation monitoring as well as electron microscopy techniques, the latter leads to dense structures for concentrations from five to ten times the critical overlap concentration during adsorption. Such conditions were found to be favorable for the formation of hollow shells. Regarding conditions for core dissolution, we demonstrated the possibility to use either ethylenediaminetetraacetic acid (EDTA) or citric acid as chelating agents. However, in some cases, it was necessary to chemically cross-link the shell to maintain its integrity.