3D Patterning within Hydrogels for the Recreation of Functional Biological Environments

Biological structures are inherently complex in nature. Structural hierarchy, chemical anisotropy, and compositional heterogeneity are ubiquitous in biological systems and play a key role in the functionality of living systems. For decades, methods such as soft lithography have enabled recreation of such arrangements through precise spatial control of molecular patterns in 2D. With technological advances and increasing understanding of molecular and structural biology, there has been an increasing interest in recreating such spatial organizations in 3D. In this review, a comprehensive summary of the latest technologies being used to create 3D patterns of functional molecules within hydrogels for tissue engineering applications is presented. The review is divided into five groups of technologies defined according to the main driving force used to fabricate the patterns including light, precise chemical design, microfluidics, 3D printing, and non‐contact forces (i.e. electric, magnetic, or acoustic fields and self‐assembly). Nature is presented in complex patterns in all taxa. Many biological processes and structures exhibit repetitive motifs of precise shape and size. Traditional and new methodologies are enabling the fabrication of patterns within 3D matter. An extensive review of technologies aiming to recreate the structural and compositional anisotropy of human tissues is presented in this article.