Abstract
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.
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