Direct Observation of Microgel Erosion via in-Liquid Atomic Force Microscopy

Abstract

Degradable hydrogel particles have been integrated into a variety of biomedical applications, but there are no studies to date illustrating the detailed morphological changes that occur in single microgels during erosion in complex media. Herein, we use ambient and in-liquid atomic force microscopy (AFM) to interrogate changes in morphology of substrate-supported microgels synthesized from poly(N-isopropylmethacrylamide-co-acrylic acid) cross-linked with a hydrolyzable cross-linker (N,O-dimethacryloyl hydroxylamine). Erosion was monitored under physiological conditions (37 °C in serum-supplemented PBS). At early time points of erosion, the microgel swelling capacity increases due to the hydrolysis of the cross-linker and a concomitant decrease in network connectivity. After longer erosion times and extensive polymer loss, the remnant degraded microgel reveals a high polymer density toward the center of the particle with a low-density corona, which most likely results from internal cross-linking of the polymer. These detailed morphological changes illustrate the complex nature of erodible microgels, which would be difficult to observe using ensemble-averaged analyses.