Bioreactors in tissue engineering: Advances in stem cell culture and three‐dimensional tissue constructs

Abstract

Bioreactors play an increasing role in tissue engineering—the generation of mammalian tissue equivalents in vitro. They can be applied for effective (stem) cell expansion, which is a crucial step concerning the fabrication of tissue engineering constructs of clinically relevant dimensions for which large cell numbers are needed. Furthermore, bioreactors are necessary for the maintenance of three‐dimensional (3D) tissue engineering constructs during cultivation ex vivo, and can be used to further stimulate the cells with a variety of physical cues. The development of novel bioreactor systems as well as mathematical modeling of their characteristics is a fast‐developing field of research. The present review provides a concise overview about recent developments in bioreactors for stem cell expansion, perfusion bioreactor systems for 3D cultures, and bioreactors for physical stimulation.

Computational fluid dynamic analysis of bioprinted self‐supporting perfused tissue models

“…the open pores on the surface and through the bulk of a 3D tissue construct (Egger et al, 2017;Gelinsky, Bernhardt, & Milan, 2015).…”

“…While this approach does provide controlled cellular perfusion, it is not suitable for solid tissues with 3D structures, which then need to be removed from the bioreactor. Direct perfusion into porous tissues applies perfusive flow directly to the open pores on the surface and through the bulk of a 3D tissue construct (Egger et al, ; Gelinsky, Bernhardt, & Milan, ). For constructs with nonuniform pore sizes and randomly oriented pores, there are unknown flow paths, unknown conduit dimensions, and unknown or poorly defined conduit shapes, thus increasing the likelihood of producing unwanted turbulent flow, subnutritious flow fields, and uneven nutrient distribution.…”

“…The drawback to using them with porous materials is the same as those presented by spinner flasks. Compression bioreactors are also capable of promoting flow in tissue constructs (Gelinsky et al, ; Kim, Sah, Grodzinsky, Plaas, & Sandy, ). However, this method is most suitable to tissues normally subjected to compression (musculoskeletal tissues) and the force/strain (as much as 10%; Kim et al, ) of compression may also result in damage or disintegration of initially delicate scaffold‐free tissues.…”

Development of surface functionalization strategies for 3D‐printed polystyrene constructs

“…Transforming PS from standard flat cell culture dishes to a 3D scaffold could provide the means to better replicate the in vivo environment by improving cell–cell interactions and enabling higher culture densities . 3D printing provides a unique avenue to rapidly manufacture and test models with biologically relevant structures; a platform that could establish clinical niches in vitro for highly replicative screening of novel pharmaceuticals, cancer therapies, and disease models . The main objective presented in this work explores engineering surface chemistry for 3D‐printed PS scaffolds to target hMSC expansion.…”

Editorial: Cell Culture Engineering

“…This represents a cheap and efficient in vitro expansion method for human immune cells. Gelinsky et al give an overview on the state of the art and recent developments for stem cell expansion, perfusion bioreactors systems for 3D cultures, and bioreactors for physical stimulation.…”