Injectable, Degradable Thermoresponsive Poly(N-isopropylacrylamide) Hydrogels

Degradable, covalently in situ gelling analogues of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) hydrogels have been designed by mixing aldehyde and hydrazide-functionalized PNIPAM oligomers with molecular weights below the renal cutoff. Co-extrusion of the reactive polymer solutions through a double-barreled syringe facilitates rapid gel formation within seconds. The resulting hydrazone cross-links hydrolytically degrade over several weeks into low molecular weight oligomers. The characteristic reversible thermoresponsive swelling-deswelling phase transition of PNIPAM hydrogels is demonstrated. Furthermore, both in vitro and in vivo toxicity assays indicated that the hydrogel as well as the precursor polymers/degradation products were nontoxic at biomedically relevant concentrations. This chemistry may thus represent a general approach for preparing covalently cross-linked, synthetic polymer hydrogels that are both injectable and degradable.