Bioengineering methods for organoid systems

Organoids have been widely used in fundamental, biomimetic, and therapeutic studies. These multicellular systems form via cell‐autonomous self‐organization where a cohort of stem cells undergoes in vivo‐like proliferation, differentiation, and morphogenesis. They also recapitulate a series of physiological cell organization, complexity and functions that are untouchable by conventional bio‐model systems using immortal cell lines. However, the development of organoids is often not easily controlled and their shape and size are yet fully physiological. Recent research has demonstrated that multiple bioengineering tools could be harnessed to control important internal and external cues that dictate stem cell behavior and stem‐cell based organoid development. In this review, we introduce the current development of organoid systems and their potentials, as well as their limitations that impede their further utility in research and clinical fields. In comparison to conventional autonomous organoid system, we then review bioengineering approaches that offer improved control over organoid growth and development. We focus on the genetic editing tools that allow the program of build‐in responses and phenotypes for organoid systems with enhanced physiological relevance. We also highlight the advances in bioengineering methods to modify cellular external milieus to generate desirable cell composition, 3D micro‐architectures, and complex microfluidic systems. We conclude that the emerging biomimetic methods that employ multidisciplinary approaches could prevail in the future development of organoid systems. Organoid models that better recapitulate organ‐specific cell types and 3D native tissue structures have many applications in development biology and disease modeling. Latest impact of bioengineering approaches to conquer limitations in self‐organized organoids has shifted the field toward rational designed organ‐on‐a‐chip constructs. This offers unprecedented opportunities in developing organoids with strong relevance of real‐world human tissues.