Methylglyoxal crosslinking increases the fracture toughness of gelatin hydrogels

Abstract

The development of biocompatible hydrogels with high strength and toughness is an ongoing challenge in many tissue engineering and drug delivery applications. Glutaraldehyde crosslinking of gelatin is widely used but increases cell toxicity. We crosslinked bovine gelatin using glutaraldehyde (Control) and methylglyoxal (MGO), a metabolic by-product during non-enzymatic collagen crosslinking, and assessed changes in the material properties of the hydrogels. Scanning electron micrographs show large pores with plate-like walls in MGO hydrogels that help retain water. Monotonic compression tests demonstrate nonlinear stress-strain behaviors. MGO samples had 96% higher moduli as compared to Control hydrogels that had moduli of 4.77 ± 0.73 kPa (n = 4). A first-order Ogden model fits the data from Control and MGO hydrogels well as compared to the Mooney-Rivlin model and neo-Hookean hyperelastic models that fit the Control samples alone. We used cavitation rheology to quantify the maximum pressure for bubble failure in the hydrogels using blunt needles with inner radii of 75, 150, 230, and 320 μm, respectively. Pressures in the bubbles increased linearly with time and dropped sharply following a critical value. High-speed videography studies demonstrate a symmetry break from large spherical bubbles in soft control hydrogels to small ellipsoidal bubbles in stiffer MGO samples. We used the critical pressures to quantify the fracture energies of the hydrogels. MGO treatment increased the fracture energy by 274% from 12.92 J/m2 for control gels. Finally, we show that analytical equations for cavitation based on Ogden and Mooney-Rivlin models present challenges when computing the fracture toughness of hydrogels.