Extrusion 3D printing of a multiphase collagen-based material: An optimized strategy to obtain biomimetic scaffolds with high shape fidelity.

Extrusion printing represents one of the leading additive manufacturing techniques for tissue engineering purposes due to the possibility of achieving accurate control of the final shape and porosity of the scaffold. Despite many polymeric materials having already been optimized for this application, the processing of biopolymer-based systems still presents several limitations mainly ascribed to their poor rheological properties. Moreover, the introduction of inorganic components into the biomaterial formulation may introduce further difficulties related to system homogeneity, finally compromising its extrudability. In this context, the present study aimed at developing a new multi-phase biomaterial ink able to mimic the native composition of bone extracellular matrix, combining type-I-collagen with nano-hydroxyapatite and mesoporous bioactive glass nanoparticles. Starting from a comprehensive rheological assessment, computational-fluid-dynamics-based models were exploited to describe the material flow regime and define the optimal printing process planning. During printing, a gelatin-based bath was exploited to support the deposition of the material, while the gelation of collagen and its further chemical crosslinking with genipin enabled the stabilization of the printed structure, characterized by high shape fidelity. The developed strategy enables the extrusion printing of complex multi-phase systems and the design of high-precision biomimetic scaffolds with great potential for bone tissue engineering.