Shape Memory Behaviors of 3D Printed Bovine Lactoferrin-PEGDA Hydrogels

Abstract

Shape memory hydrogels have emerged as a compelling class of stimuli-responsive soft matter, offering geometric reconfigurability for application in soft robotics, bioelectronics, and tissue engineering. While protein-based hydrogels represent a biologically derived and functionally rich platform for shape memory systems, globular proteins in this context represents an under-explored class of proteins. Here, we report the use of bovine lactoferrin (bLF), an iron-binding globular glycoprotein from bovine milk, as a structural building block for a photo-curable bLF-poly(ethylene glycol) diacrylate (PEGDA) resin compatible with digital light processing (DLP) based 3D printing. The printed hydrogels retained iron-binding functionality after photocrosslinking, suggesting that bLF’s native conformational properties were largely preserved within the crosslinked network. The mechanical properties of the printed hydrogels were highly stimuli-dependent. Relative to the as-printed state in Phosphate-Buffered Saline (PBS, E = 43.9 kPa), iron supplementation nearly doubled the Young’s modulus to 80.1 kPa, whereas immersion in acidic solution (pH 2) softened the network, reducing the modulus to 31.0 kPa. A broader screen across metal ions revealed that this mechanical tunability is a general feature of bLF's metal-binding functionality: hydrogels equilibrated in solutions of iron, magnesium, calcium, zinc, copper, cobalt, and nickel exhibited Young's moduli spanning 16.8 to 65.8 kPa, indicating that metal identity is itself a design parameter. The pH-responsive mechanical response was further utilized during a shape memory cycle, where immersion in pH 2 solution enabled programmed deformation of the construct, which was then restored to 90% of its original geometry after immersion in phosphate-buffered saline (pH 7.4). Coupling this iron-binding functionality with a bilayer architecture enabled iron-triggered directional actuation, providing a second, mechanistically distinct route to programmed shape change. This work establishes bLF as a feedstock for photocrosslinkable 3D printed shape memory hydrogels, demonstrating that its unique metal-binding and pH-responsive conformational properties can be harnessed as a molecularly encoded switch in soft matter systems.