Integrating self-assembly and biofabrication for the development of structures with enhanced complexity and hierarchical control

Nature has evolved to grow and regenerate tissues and organs using self-assembling processes capable of organizing a wide variety of molecular building-blocks at multiple size scales. As the field of biofabrication progresses, it is essential to develop innovative ways that can enhance our capacity to build more complex macroscopic structures using molecular and nanoscale components in a rational manner. In this review, we highlight the emerging opportunities, advantages, and challenges of incorporating self-assembly with biofabrication for the development of more biologically relevant, active, and functional structures. The review is organized in four sections. First, to better appreciate the benefits of this integrated approach, we summarize recent advances in self-assembly and biofabrication aimed at improving hierarchical control. Then, we discuss work focused on combining self-assembly with biofabrication in three areas including a) conventional bioprinting techniques using self-assembling bioinks; b) new methods where self-assembly drives the fabrication process, and c) techniques based on cellular self-assembly. The ultimate goal of this review is to emphasize the importance of structural hierarchy in biological systems and to highlight the potential behind the integration of biofabrication and self-assembly towards the development of more functional structures for tissue engineering and regenerative medicine.