Organoid bioprinting to pattern the matrix microenvironment

Abstract

The development of organoid cultures has propelled the fields of cell biology, tissue engineering, and regenerative medicine forward. These cultures better mimic in vivo tissue structure and function compared to 2D cell culture; however, organoids are limited in size and do not inherently allow precise control over tissue architecture and cell heterogeneity. Hand-wrought organoid biofabrication approaches enable the production of larger and more complex tissues, but they still lack reproducible control of spatiotemporal tissue patterns. In contrast, bioprinting is a collection of machine-wrought technologies that are emerging as powerful tools in tissue engineering and disease modeling, but have not yet been widely applied to organoids. When combined with advances in biomaterials science, bioprinting offers the possibility to control spatiotemporal cellular and microenvironmental features. The interactions between biomaterial inks, support baths, and embedded cells provide the opportunity to guide the maturation and functionality of engineered tissues. This review describes how recent advances in organoid technology, bioprinting, and biomaterials science can be integrated to achieve spatiotemporal patterning of four aspects of the microenvironment: matrix structure and mechanics, matrix ligands and morphogens, co-culture of multiple cell types, and incorporation of vasculature. These insights underscore the potential for organoid bioprinting to advance the fabrication of in vitro tissue mimics for applications in drug screening, disease modeling, and regenerative medicine.