Measurement and Comparison of Hyaluronic Acid Hydrogel Mechanics Across Length Scales

Abstract

Hydrogels are an important class of biomaterials that are being developed for use in medicine, such as in drug delivery and tissue engineering applications. To improve properties (e.g., injectability, nutrient transport, cell invasion), hydrogels are often processed as hydrogel microparticles (microgels) that can be used as suspensions or jammed into granular hydrogels. The mechanical properties of microgels are important across length scales, from macroscale bulk properties of granular assemblies to microscale interactions with cells; however, microgel mechanics are rarely reported due to challenges in their measurement. To address this, we report here a cost-effective, easy-to-use do-it-yourself (DIY) active feedback micropipette aspiration device to quantify the mechanics of individual microgels. Using norbornene-modified hyaluronic acid (NorHA) synthesized via an environmentally friendly, aqueous reaction as an exemplary hydrogel, we compare hydrogel mechanics across scales at various macromer concentrations. Hydrogels tested via uniaxial compression exhibit similar moduli values, trends of increasing modulus with increasing macromer concentration, and mechanical stability over time to the same formulations processed as microgels via batch emulsions (~170 μm) and tested via micropipette aspiration. Moduli range from ~50 to ~100 kPa as the NorHA macromer concentration increases from 3 wt% to 5 wt%. These findings are validated by testing with spherical nanoindentation, with similar moduli measured. Collectively, this work provides an accessible device that allows for the rapid testing of microgel mechanical properties, while also improving our understanding of hydrogel mechanics across scales for use in the design of microgels for biomedical applications.