Injectable or in situ-gelling hydrogels have attracted significant interest across a range of applications including drug delivery, tissue engineering, additive manufacturing, and biosensors based on their capacity to form well-defined hydrogels from low viscosity precursor polymers without the need for any additional external or catalytic processing steps. However, such systems also present inherent challenges when higher mechanical strength hydrogels are required since there are few options available for enhancing mechanics while maintaining facile injectability. This is particularly true in the context of in vivo injections, in which any toughening strategy must be both biocompatible and practically implemental via minimally or non-invasive strategies. In response, we are developing new strategies for enhancing the elasticity and toughness of in situ-gelling hydrogels based on hydrazone crosslinked thermoresponsive polymers, of practical interest for enabling dynamic switching of cell adhesion for tissue engineering (in which gel mechanics are critical for success) and on-demand drug delivery. First, we have developed dynamically-crosslinked interpenetrating networks by co-extruding pairs of kinetically orthogonal electrophiles (aldehyde-functionalized poly(N-isopropylacrylamide) (PNIPAM) and maleimide-functionalized poly(N-vinylpyrrolidone) (PVP)) and nucleophiles (hydrazide-functionalized PNIPAM and thiolated PVP) using a double barrel syringe. The resulting structures offered both enhanced mechanics and reduced hysteresis of the thermoresponsive phase transition. Second, we have shown that anisotropic cellulose nanocrystals (CNCs) can enhance the mechanics of hydrazone-crosslinked poly(oligoethylene glycol methacrylate) (POEGMA) hydrogels via a combined interfacial and filler effect, increasing the storage modulus up to 35-fold compared to the hydrogel alone at &lt;5 wt% CNC content. Such mechanical enhancement enables, for example, improved cell growth and the capacity to create wrinkled 2.5D hydrogel films with well-defined and optionally oriented patterns using shrinkable polystyrene. In addition, the alignment of the anisotropic CNCs via either directional freezing or diamagnetic alignment can enable anisotropic toughening of the hydrogel in a defined direction, in the latter case even upon injection in vivo. Both strategies offer new alternatives to improve the mechanics of in situ-gelling hydrogels to broaden their potential applications.

Engineering the mechanics of injectable environmentally responsive hydrogels

2019 Fall National Meeting

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