Embedded 3D Bioprinting of Collagen Inks into Microgel Baths to Control Hydrogel Microstructure and Cell Spreading

Abstract

Microextrusion‐based 3D bioprinting into support baths has emerged as a promising technique to pattern soft biomaterials into complex, macroscopic structures. We hypothesized that interactions between inks and support baths, which are often composed of granular microgels, could be modulated to control the microscopic structure within these macroscopic‐printed constructs. Using printed collagen bioinks crosslinked either through physical self‐assembly or bioorthogonal covalent chemistry, we demonstrate that microscopic porosity is introduced into collagen inks printed into microgel support baths but not bulk gel support baths. The overall porosity is governed by the ratio between the ink's shear viscosity and the microgel support bath's zero‐shear viscosity. By adjusting the flow rate during extrusion, the ink's shear viscosity was modulated, thus controlling the extent of microscopic porosity independent of the ink composition. For covalently crosslinked collagen, printing into support baths comprised of gelatin microgels (15‐50 µm) resulted in large pores (∼40 µm) that allowed human corneal mesenchymal stromal cells to readily spread, while control samples of cast collagen or collagen printed in non‐granular support baths did not allow cell spreading. Taken together, these data demonstrate a new method to impart controlled microscale porosity into 3D printed hydrogels using granular microgel support baths.This article is protected by copyright. All rights reserved