Smart Hydrogels and Biomaterials
Smart Hydrogels and Biomaterials

NAT runs an intensive development program in the polymer-based smart hydrogels that are responsive to the environmental stimulus such as temperature, ionic strength, pH, and other factors (1).

In particular, we developed in situ cross-linkable hydrogels based on biocompatible and biodegradable polymers - hyaluronic acid (HA) and poly(ethylene glycol) (PEG). Related polymers precursors are liquids that may be conveniently delivered to a desired tissue, where they form hydrogels in situ. The hydrogels gradually degrade in vivo by chemical or enzymatic processes, forming non-toxic and easily eliminated fragments. The in situ forming PEG and HA hydrogel systems have a potential to be used in a delivery of biomaterials, cell encapsulation and tissue regeneration processes.

PEG Hydrogels: Formation of hydrogels is achieved when multiple-arm functionalized PEG polymer precursors react with a suitable cross-linking moiety. The linkers’ architecture is designed to render them hydrolytically-labile. That leads to an efficient cleavage and degradation to smaller fragments naturally eliminated by renal filtration. We can control hydrogel properties by the PEG concentration, functionality, molecular weight and pH, and fine-tune the system to a particular application.

Thiolated HA Hydrogels: We have developed a proprietary method of introducing thiol groups into HA. The thiolated HA precursors are low viscosity solutions stable at pH=3-4, which are easy to handle and apply. Gelation occurs with a pH adjustment to 7.0-7.4 in presence of oxygen from air that oxidizes thiol groups with a formation of the disulfide cross-links. The gelation time and properties of the gel can be exquisitely regulated by the thiol content, HA concentration, pH, and temperature. Our approach avoids byproduct formation, exothermic reactions, and potential toxicity inherent to many hydrogel cross-linkers.

(1) J.R. Moreira, L.S. Teixeira, A. Krouwels, P.J. Dijkstra, C.A .van Blitterswijk , M. Karperien , J. Feijen, “Synthesis and Characterization of Hyaluronic Acid-poly(ethylene glycol) Hydrogels via Michael Addition: An Injectable Biomaterial for Cartilage Repair”, Acta Biomater. , 2010, 6(6), pp. 1968-1977.