Nanostructure of Fully Injectable Hydrazone–Thiosuccinimide Interpenetrating Polymer Network Hydrogels Assessed by Small-Angle Neutron Scattering and dSTORM Single-Molecule Fluorescence Microscopy

• Published in: ACS applied materials & interfaces 2017-12, Vol.9 (48), p.42179-42191
• Main Authors: Gilbert, Trevor, Alsop, Richard J, Babi, Mouhanad, Moran-Mirabal, José, Rheinstädter, Maikel C, Hoare, Todd
• Format: Article
• Language: English
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.7b11637

Herein, we comprehensively investigate the internal morphology of fully injectable interpenetrating networks (IPNs) prepared via coextrusion of functionalized precursor polymer solutions based on thermoresponsive poly­(N-isopropylacrylamide) (PNIPAM) and nonthermoresponsive poly­(vinyl pyrrolidone) (PVP) by reactive mixing using kinetically orthogonal hydrazone and thiosuccinimide cross-linking mechanisms. Small-angle neutron scattering, probing both the full IPN as well as the individual constituent networks of the IPN using index-matching, suggests a partially mixed internal structure characterized by PNIPAM-rich domains entrapped in a clustered PVP-rich phase. This interpretation is supported by super-resolution fluorescence microscopy (direct stochastic optical reconstruction microscopy) measurements on the same gels on a different length scale, which show both the overall phase segregation typical of an IPN as well as moderate mixing of PNIPAM into the PVP-rich phase. Such a morphology is consistent with the kinetics of both gelation and phase separation in this in situ gelling system, in which gelation effectively traps a fraction of the PNIPAM in the PVP phase prior to full phase separation; by contrast, such interphase mixing is not observed in semi-IPN control hydrogels. This knowledge has significant potential for the design of an injectable hydrogel with internal morphologies optimized for particular biomedical applications.