Injectable Interpenetrating Network Hydrogels via Kinetically Orthogonal Reactive Mixing of Functionalized Polymeric Precursors

The enhanced mechanics, unique chemistries, and potential for domain formation in interpenetrating network (IPN) hydrogels have attracted significant interest in the context of biomedical applications. However, conventional IPNs are not directly injectable in a biological context, limiting their potential utility in such applications. Herein, we report a fully injectable and thermoresponsive interpenetrating polymer network formed by simultaneous reactive mixing of hydrazone cross-linked poly(N-isopropylacrylamide) (PNIPAM), and thiosuccinimide cross-linked poly(N-vinylpyrrolidone) (PVP). The resulting IPN gels rapidly (<1 min) after injection without the need for heat, UV irradiation, or small-molecule cross-linkers. The IPNs, cross-linked by kinetically orthogonal mechanisms, showed a significant synergistic enhancement in shear storage modulus compared to the individual component networks as well as distinctive pore morphology, degradation kinetics, and thermal swelling; in particular, significantly lower hysteresis was observed over the thermal phase transition relative to single-network PNIPAM hydrogels.