Injectable Poly(N‑isopropylacrylamide)/Poly(vinylpyrrolidone) Interpenetrating Network Hydrogels Formed via Hydrazone/Disulfide Cross-Linking

Injectable in situ gelling interpenetrating network hydrogels in which both interpenetrating phases can independently gel upon injection offer significant potential in applications if their internal structure can be rationally controlled. Herein, we report the fabrication and nanostructural characterization of poly­(N-isopropylacrylamide) (PNIPAM)/poly­(vinylpyrrolidone) (PVP) injectable interpenetrating polymer networks constructed based on a combination of hydrazone (PNIPAM) and disulfide (PVP) cross-linking. Compared to previously reported hydrazone/thiosuccinimide IPN formation, disulfide cross-linking is significantly slower than hydrazone cross-linking, enabling the generation of tunable internal phase morphologies in the injectable IPNs as a function of PVP molecular weight and degree of thiolation. Results from bulk rheology, polarity-sensitive fluorescence measurements, STORM super-resolution fluorescence microscopy, and contrast-matched small-angle neutron scattering measurements suggest that domain formation on the SANS-accessible length scale is driven by the rapid PNIPAM gelation that largely excludes PNIPAM from the PVP-rich domains but results in significant PVP entrapment within the PNIPAM-rich domain. Furthermore, PVP precursor polymers with lower molecular weights (i.e., reduced viscosities) and/or lower degrees of thiolation result in IPNs that undergo significant structural reconfiguration upon heating above the volume phase transition of the PNIPAM phase, a result correlated to the capacity of the thermodynamically favorable PNIPAM phase transition to reconfigure the weaker and dynamic PVP-disulfide phase to maximize the degree of PNIPAM phase collapse. Overall, regulating the relative gelation kinetics of the two interpenetrating in situ gelling phases results in tunable morphologies of relevance to the potential applications of such materials.