Droplet-based bioprinting for fabrication of tumor spheroids

Cancer is now one of the leading causes of mortality worldwide, and the cancer treatment development is still slow due to the lack of efficient in vitro tumor models for studying tumorigenesis and facilitating drug development. Multicellular tumor spheroids can recapitulate the critical properties of tumors in vivo, including spatial organization, physiological responses, and metabolism, and are considered powerful platform for disease study and drug screening. Although several spheroid fabrication methods have been developed, most of them result in uncontrolled cell aggregations, yielding spheroids of variable size and function. Droplet-based bioprinting is capable of depositing cells in spatiotemporal manner so as to control the composition and distribution of printed biological constructs, thereby facilitating high-throughput fabrication of complicated and reproducible tumor spheroids. In this review, we introduce the progress of droplet-based bioprinting technology for the fabrication of tumor spheroids. First, different droplet-based bioprinting technologies are compared in terms of their strengths and shortcomings, which should be taken into account while fabricating tumor spheroids. Second, the latest advances in modeling distinct types of cancers and the enabled applications with tumor spheroids are summarized. Finally, we discuss the challenges and potentials revolving around the advances of bioprinting technology, improvement of spheroid quality, and integration of different technologies.