Freeze-drying is a well-established process in biomedical engineering for the fabrication of three-dimensional open-porous medical devices, especially those based on biopolymers. One of the most used biopolymers in this field is collagen, the most abundant protein in the human body and the main component of the extracellular-matrix, as well as its derivatives. Freeze-dried collagen-based sponges with a wide variety of attributes can be produced by design and have led to a wide range of successful commercial medical devices, foremost for dental, orthopedic, hemostatic and neuronal applications. However, this is still considered a high-cost and time-consuming process that is often used in a non-optimized manner. By combining advances in other technological fields, the opportunity arises to further evolve this process in a sustainable manner, and optimize the resulting products as well as create new opportunities in this field.