Towards manufacturing of human organoids.

Organoids are 3D miniature versions of organs produced from stem cells derived from either patient or healthy individuals in vitro that recapitulate the actual organ. Organoid technology has ensured an alternative to pre-clinical drug testing as well as being currently used for "personalized medicine" to modulate the treatment as they are uniquely identical to each patient's genetic makeup. Researchers have succeeded in producing different types of organoids and have demonstrated their efficient application in various fields such as disease modeling, pathogenesis, drug screening and regenerative medicine. There are several protocols for fabricating organoids in vitro. In this comprehensive review, we focus on key methods of producing organoids and manufacturing considerations for each of them while providing insights on the advantages, applications and challenges of these methods. We also discuss pertinent challenges faced during organoid manufacturing and various bioengineering approaches that can improve the organoid manufacturing process. Organoids size, number and the reproducibility of the fabrication processes are touched upon. The major factors which are involved in organoids manufacturing such as spatio-temporal controls, scaffold designs/types, cell culture parameters and vascularization have been highlighted.