Smart Hydrogels and Biomaterials

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

In particular, we have developed in situ cross-linkable hydrogels based on biocompatible and biodegradable polymers—hyaluronic acid (HA) and poly(ethylene glycol) (PEG). Related polymer precursors are liquids that may be conveniently delivered to 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. In-situ-forming PEG and HA hydrogel systems can 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 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 the presence of oxygen from air, which 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 by-product 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.