A Small‐Molecule Polycationic Crosslinker Boosts Alginate‐Based Bioinks for Extrusion Bioprinting

Abstract

AbstractThe importance of bioink suitability for extrusion bioprinting tissue‐like constructs cannot be overemphasized. Owing to their excellent accessibility, alginate (Alg) ‐based bioinks are widely used. However, the printability accuracy and post‐printing stability of current Alg‐based bioinks remain challenging, especially for large‐size fabrication. Herein, an improvement strategy for pre‐crosslinking and post‐crosslinking of methacrylated Alg (AlgMA) bioinks in extrusion bioprinting is presented via introduction of methacrylated ɛ‐polylysine (ɛ‐PLMA) as a small‐molecule polycationic crosslinker. Due to their electrostatic interaction and covalent bonding, ɛ‐PLMA significantly reinforce the operability and prolong stability of AlgMA bioinks, in comparison with single‐molecule Ca2+ or large‐molecule methacrylated gelatin as pre‐crosslinkers. Meanwhile, attributed to their regulation of a charged microenvironment (−345.25 to 121.55 mV) and hydrophilicity (26.64° to 52.00°), the cells in bioprinted AlgMA/PLMA constructs demonstrated improved viability and vitality. Therefore, such a strategy of introducing small‐molecule cationic crosslinker ɛ‐PLMA is a promising booster for improving Alg‐based extrusion bioprinting, potential to extend its biomedical applications.