Multi-Material Extrusion-Based 3D Printing of Hybrid Scaffolds for Tissue Engineering Application

Additive manufacturing of hydrogel-based scaffolds requires concurrent control of material rheology and extrusion dynamics, especially in multi-material architectures. In this work, we develop a modular multi-material extrusion-based 3D-printing platform that combines a filament-fed extruder for thermoplastic polymers with a piston-driven extruder for viscous gel inks, together with an empirical calibration procedure for gel dosing. The calibration algorithm optimizes the pre-extrusion and retraction displacement (E_Pr/R) based on stepwise extrusion experiments and reduces the discrepancy between theoretical and measured deposited mass for shear-thinning alginate gels to below the prescribed tolerance. The calibrated system is then used to fabricate two representative hybrid constructs: partially crosslinked sodium alginate scaffolds with an internal hollow channel supported by a removable polycaprolactone framework, and self-supporting structures based on a sodium alginate-chitosan polyelectrolyte complex obtained by sequential co-extrusion. The resulting constructs remain mechanically stable after ionic crosslinking and solvent treatment and can subsequently be converted into highly porous scaffolds by freeze- or supercritical drying. The proposed combination of hardware architecture and extrusion calibration enables reproducible multi-material 3D printing of hydrogel-thermoplastic hybrid scaffolds and can be readily adapted to other gel-based inks for tissue engineering applications.