Recent advances in bioreactors for cell-based therapies [version 1; referees: 2 approved]

Bioreactors have become indispensable tools in the cell-based therapy industry. Various forms of bioreactors are used to maintain well-controlled microenvironments to regulate cell growth, differentiation, and tissue development. They are essential for providing standardized, reproducible cell-based products for regenerative medicine applications or to establish physiologically relevant in vitro models for testing of pharmacologic agents. In this review, we discuss three main classes of bioreactors: cell expansion bioreactors, tissue engineering bioreactors, and lab-on-a-chip systems. We briefly examine the factors driving concerted research endeavors in each of these areas and describe the major advancements that have been reported in the last three years. Emerging issues that impact the commercialization and clinical use of bioreactors include (i) the need to scale up to greater cell quantities and larger graft sizes, (ii) simplification of in vivo systems to function without exogenous stem cells or growth factors or both, and (iii) increased control in the manufacture and monitoring of miniaturized systems to better capture complex tissue and organ physiology