(668g) Non-Equilibrium Characterization of Injectable Polymer Nanoparticle Hydrogels

The mechanical properties of injectable hydrogels are critical to their function in a broad range of translational applications, ranging from regenerative medicine to cancer immunotherapy. Specifically, the microstructure and supramolecular interactions of a hydrogel inform the yielding behavior during injection and mechanical properties post-injection in vivo. Polymer-Nanoparticle (PNP) hydrogels are one class of injectable hydrogels composed of a hydrophobically-modified cellulose scaffold and degradable (poly)ethylene glycol (poly)lactic acid (PEG-PLA) nanoparticles. These components interact to form a dynamic, physically-crosslinked entropically-driven hydrogel network. PNP interactions lead to complex rheological characteristics, such as shear-thinning, self-healing, and tunable yield stress and extensibility, as well as tunable mass transfer characteristics, making PNP hydrogels excellent candidates for use as vehicles for cellular and protein therapeutics. However, there is still a distinct gap in rheological and thermodynamic measurements of dynamic PNP systems. Traditional rheological measurements taken in the linear viscoelastic regime have little relevance to the high-shear, post-yield nonlinear regime of injection, in which the PNP network is out of thermodynamic equilibrium. Additionally, to study the driving forces behind the PNP interactions, isothermal titration calorimetry (ITC) experiments have been used, which only extract thermodynamic equilibrium, not kinetic, data. In this talk, I will show the use of dynamic, non-equilibrium characterization techniques to probe previously unexplored features of PNP hydrogels. We prepared a library of cellulose polymers with varying hydrophobic modifications to systematically study the PNP interaction and its effect on the hydrogel rheological properties. I will demonstrate both small and large-angle oscillatory shear (LAOS) measurements and subsequent Sequence of Physical Processes (SPP) LAOS analysis [1] that demonstrate key differences in yielding behavior between PNP hydrogels. Critically, I will show that the yielding process of the PNP hydrogels cannot be defined by a single yield stress value and is more accurately described by a range and velocity of yielding. I will use ITC and the novel analysis, kinetic ITC (kinITC) [2], to show joint thermodynamic and kinetic measurements of the PNP interaction and gain further understanding of the microstructure of PNP hydrogels. The kinetic data from kinITC will further elucidate the nature and strength of the noncovalent interactions. Overall, the work presented here bridges the small length-scale microstructural chemical characterization of the materials to their higher length-scale mechanical rheological properties, establishing a new way of thinking about materials selection for hydrogels in translational applications.

[1] Rogers, S. A. (2012). A sequence of physical processes determined and quantified in LAOS: An instantaneous local 2D/3D approach. Journal of Rheology, 56, 1129. https://doi.org/10.1122/1.4726083

[2] Burnouf, D., Ennifar, E., Guedich, S., Puffer, B., Hoffmann, G., Bec, G., Disdier, F., Baltzinger, M., & Dumas, P. (2012). KinITC: A new method for obtaining joint thermodynamic and kinetic data by isothermal titration calorimetry. Journal of the American Chemical Society, 134(1), 559–565. https://doi.org/10.1021/JA209057D/SUPPL_FILE/JA209057D_SI_001.PDF