Organs are complex systems composed of different cells, proteins and signalling molecules that are arranged in a highly ordered structure to orchestrate a myriad of functions in our body. Biofabrication strategies can be applied to engineer 3D tissue models in vitro by mimicking the structure and function of native tissue through the precise deposition and assembly of materials and cells. This approach allows the spatiotemporal control over cell-cell and cell-extracellular matrix communication and thus the recreation of tissue-like structures. In this Review, we examine biofabrication strategies for the construction of functional tissue replacements and organ models, focusing on the development of biomaterials, such as supramolecular and photosensitive materials, that can be processed using biofabrication techniques. We highlight bioprinted and bioassembled tissue models and survey biofabrication techniques for their potential to recreate complex tissue properties, such as shape, vasculature and specific functionalities. Finally, we discuss challenges, such as scalability and the foreign body response, and opportunities in the field and provide an outlook to the future of biofabrication in regenerative medicine.

A microfluidic system was used to prepare a large number of size‐controlled collagen gel beads to form microtissue units, “cell beads”, as tissue building blocks. By stacking cell beads into a doll‐shaped silicone chamber, millimeter‐thick tissue with uniform cell density was formed rapidly. The bead structure allowed the application into the 3D printing, achieving automated geometrical control of the formed tissues for the fabrication of functional complex tissues.

Biohybrid robots are attracting attention as promising candidates to enhance robot applicability to studies on biological designs and in vitro construction of biological dynamic systems. Rapid progress in biohybrid robots with skeletal muscle tissues formed on a flexible substrate has enabled various types of locomotion powered by muscle tissue. However, it has been difficult to achieve high levels of both large and long-term actuations of the skeletal muscle tissues because of their spontaneous shrinkage through the course of the tissue culture. To overcome this limitation, we adapted the concept of biological systems and developed a biohybrid robot actuated by an antagonistic pair of skeletal muscle tissues. Our robot achieved large actuation (~90° of rotation of a joint) by selective contractions of the skeletal muscle tissues and a long lifetime (~1 week) by balancing tensions of the antagonistic tissues to prevent the spontaneous shrinkage. As a demonstration, we showed that our biohybrid robots allowed a pick-and-place manipulation of objects. This research may provide a platform to exceed the limitations of design in conventional biohybrid robots and replicate various lifelike movements.

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