3D Bioprinting of Highly Thixotropic Alginate/Methylcellulose Hydrogel with Strong Interface Bonding

Abstract

A robust alginate/methylcellulose (Alg/MC) blend hydrogel, with a strategy to improve adhesion between printed layers, has been fabricated for the first time for three-dimensional (3D) bioprinting. The optimized Alg/MC blend hydrogel exhibits a highly thixotropic property, great extrudability, and stackability. With treatment by a trisodium citrate (TSC) solution, the interfacial bonding between the printed layers is significantly improved. The TSC solution acts as a chelating agent to remove the superficial calcium ions at each layer. Post-cross-linking in a CaCl₂ bath after 3D printing further enhances the adhesion strength between the layers. The key parameters affecting the interfacial strength of the Alg/MC hydrogel are found to be the concentration of TSC, the volume of TSC, and the concentration of CaCl₂ in the bath. The Alg/MC hydrogel with the aid of TSC demonstrates superior printability, high stackability (150 layers can be printed), and high shape fidelity. A good cell viability of >95% is obtained for a freshly 3D-bioprinted Alg/MC construct. The novel Alg/MC hydrogel with the aid of TSC has been shown to have a great potential as an advanced 3D bioprinting material.