Document Type



Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence


Medical engineering


The biofabrication of large scaffolds from natural biomaterials into complex 3D shapes with controllable microarchitecture remains a major challenge. Freeze-drying (or lyophilization) is a technique used to create bioactive scaffolds with a porous architecture and is typically only used to generate scaffolds in planar 3D geometries. Here we report the development of a new biofabrication process to form a collagen-based scaffold into a large, complex geometry which has a large height to width ratio, and a controlled porous microarchitecture. This biofabrication process was validated through the successful development of a heart valve shaped scaffold, fabricated from a collagen-glycosaminoglycan co-polymer. Notably, despite the significant challenges in using freeze-drying to create such a structure, the resultant scaffold had a uniform, homogeneous pore architecture throughout. This was achieved through optimization of the freeze-drying mold and freezing parameters. We believe this to be the first demonstration of using freeze-drying to create a large, complex scaffold geometry with a controlled, porous architecture using natural materials. This study validates the potential of using freeze-drying for development of organ-specific scaffold geometries for tissue engineering applications, which up until now might not have been considered feasible.