Block Polyelectrolyte Additives Modulate the Viscoelasticity and Enable 3D Printing of Gelatin Inks at Physiological Temperatures

Abstract

We demonstrate the utility of block polyelectrolyte (bPE) additives to enhance viscosity and resolve longstanding challenges with the three-dimensional printability of extrusion-based biopolymer inks. The addition of oppositely charged bPEs into solutions of photocurable gelatin methacryloyl (GelMA) results in complexation-driven self- assembly of the bPEs, leading to GelMA/bPE inks that are printable at physiological temperatures, representing stark improvements over GelMA inks that suffer from low viscosity at 37 °C leading to low printability and poor structural stability. The hierarchical microstructure of the self-assemblies (either jammed micelles or three-dimensional networks) formed by the oppositely charged bPEs, as confirmed by small angle X-ray scattering, is attributed to the enhancements in the shear strength and printability of the GelMA/bPE inks. Varying bPE concentration in the inks is shown to enable tunability of the rheological properties to meet the criteria of pre- and post-extrusion flow characteristics for 3D bioprinting, including prominent yield stress behavior, strong shear thinning, and rapid recovery upon flow cessation. Moreover, the bPE self-assemblies also contribute to the robustness of the photocrosslinked hydrogels – photocrosslinked GelMA/bPE hydrogels are shown to exhibit higher shear strength than photocrosslinked GelMA hydrogels. We envision this study to serve as a practical guide for the bioprinting of bespoke extrusion inks where bPE are used as scaffolds and viscosity enhancers that can be emulated in a range of biopolymers and photocurable precursors.

Advances, Applications, and Emerging Opportunities in Electrostatic Hydrogels

“…This allows for the fabrication of defect-free scaffolds in which the dissolution of bPE chains and biodegradation of the bioink allow cell growth and proliferation (Figure 5c). 46,50 Cell Scaffolds and Artificial ECMs. The ability to control PEC hydrogel moduli through the precise design of synthetic bPEs has promoted their use as synthetic cell scaffolds for tissue engineering.…”