Bioprinting of Complex Multicellular Organs with Advanced Functionality-Recent Progress and Challenges Ahead.

Bioprinting has emerged as one of the most promising strategies for fabrication of functional organs in the lab as an alternative to transplant organs. While progress in the field has mostly been restricted to a few miniaturized tissues with minimal biological functionality until a few years ago, recent progress has advanced the concept of building three-dimensional multicellular organ complexity remarkably. This review discusses a series of milestones that have paved the way for bioprinting of tissue constructs that have advanced levels of biological and architectural functionality. Critical materials, engineering and biological challenges that are key to addressing the desirable function of engineered organs are presented. These are discussed in light of the many difficulties to replicate the heterotypic organization of multicellular solid organs, the nanoscale precision of the extracellular microenvironment in hierarchical tissues, as well as the advantages and limitations of existing bioprinting methods to adequately overcome these barriers. In summary, the advances of the field toward realistic manufacturing of functional organs have never been so extensive, and this manuscript serves as a road map for some of the recent progress and the challenges ahead.