Probing the Internal Morphology of Injectable Poly(oligoethylene glycol methacrylate) Hydrogels by Light and Small-Angle Neutron Scattering

While injectable, in situ gelling hydrogels have attracted increasing attention in the biomedical literature due to their minimally invasive administration potential, little is known about the internal morphology of these hydrogels and thus how to engineer precursor polymer compositions to achieve desired hydrogel properties. In this paper, the internal morphology of injectable in situ gelling hydrogels based on hydrazide and aldehyde-functionalized poly(oligoethylene glycol methacrylate) precursors with varying lower critical solution temperatures (LCSTs) is investigated using a combination of spectrophotometry, small-angle neutron scattering, and light scattering. If two precursor polymers with similar LCSTs are used to prepare the hydrogel, relatively homogeneous hydrogels are produced (analogous to conventional step-growth polymerized hydrogels); this result is observed provided that gelation is sufficiently slow for diffusional mixing to compensate for any incomplete mechanical mixing in the double-barrel syringe and the volume phase transition temperature (VPTT) of the hydrogel is sufficiently high that phase separation does not occur on the time scale of gelation. Hydrogels prepared from precursor polymers with different LCSTs (1 polymer/barrel) also retain transparency, although their internal morphology is significantly less homogeneous. However, if functionalized polymers with different LCSTs are mixed in each barrel (i.e., 2 polymers/barrel, such that a gelling pair of precursors with both low and high LCSTs is present), opaque hydrogels are produced that contain significant inhomogeneities that are enhanced as the temperature is increased; this suggests phase separation of the hydrogel into lower and higher LCST domains. Based on this work, the internal morphology of injectable hydrogels can be tuned by engineering the gelation time and the physical properties (i.e., miscibility) of the precursor polymers, insight that can be applied to improve the design of such hydrogels for biomedical applications.