Exploring the tunable micro-/macro-structure enabled by alginate-gelatin bioinks for tissue engineering

Abstract

This study explores the development of optimized alginate-gelatin (AG) bioinks for advanced 3D bioprinting applications, particularly in tissue engineering. Central to our investigation is the establishment of a method for producing AG bioinks with highly tunable viscoelastic properties and the ability to create both macro- and micro-porous scaffolds through a liquid-liquid emulsion technique applied to chemically crosslinked hydrogels and shaped by microextrusion. Our methodology encompasses a comprehensive evaluation of homogenization, pasteurization techniques, and rheological assessments to optimize the mechanical properties of AG hydrogels, ensuring their suitability for bioprinting.

The study demonstrates that dynamic homogenization and conventional pasteurization methods yield superior dissolution and sterility of the bioinks, crucial for maintaining optical quality and biological compatibility. Crosslinking optimization significantly enhanced the elasticity and reduced post-crosslinking shrinkage of the hydrogels, a key factor in achieving desired cell viability and function within the engineered tissues. The incorporation of porosity through a controlled liquid-liquid emulsion process was found to enhance cellular interactions and integration within the bioprinted constructs.

Our findings confirm that the rheological properties of bioinks play a crucial role in determining bioprintability, with temperature modulation emerging as a key tool for tailoring these characteristics. The biocompatibility and functional performance of the AG hydrogels were validated through in vitro experiments, demonstrating promising cell viability and proliferation. This research lays the groundwork for the development of advanced bioinks capable of supporting complex tissue architectures in regenerative medicine and tissue engineering. By marrying the versatility of alginate and gelatin with innovative fabrication techniques, our study advances the frontier of 3D bioprinting, paving the way for the creation of biomimetic tissues with enhanced physiological relevance and therapeutic potential.