A multiparallel bioreactor for the cultivation of mammalian cells in a 3D‐ceramic matrix

Abstract

For adherently growing cells, cultivation is limited by the provided growth surface. Excellent surface-to-volume ratios are found in highly porous matrices, which have to face the challenge of nutrient supply inside the matrices' caverns. Therefore, perfusion strategies are recommended which often have to deal with the need of developing an encompassing bioreactor periphery. We present a modular bioreactor system based on a porous ceramic matrix that enables the supply of cells with oxygen and nutrients by perfusion. The present version of the reactor system focuses on simple testing of various inoculation and operation modes. Moreover, it can be used to efficiently test different foam structures. Protocols are given to set-up the system together with handling procedures for long-time cultivation of a CHO cell line. Experimental results confirm vital growth of cells inside the matrices' caverns.

Microbioreactor design for 3‐D cell cultivation to create a pharmacological screening system

“…According to 3‐D cell culture research publications in the past 20 years, there is an exponentially growing interest in the development of microfluidic devices for culturing cells [http://www.3dcellculture.com/]. New possible applications in biotechnology and medicine including current issues like stem cell research and tissue engineering accelerate the fusion of micro system technology and biological research 1–4. Further, application of 3‐D cell cultures is especially relevant for ADME/Tox testing, in particular using hepato‐ or keratinocytes.…”

“…Conventionally, preclinic drug development includes cellular cultivation and testing of toxicity and ADME parameters in monolayer cultures (2‐D culture). Nevertheless, it has been widely assumed that 3‐D cell culture systems may provide useful tools that could lead to a gain of information regarding extracellular interactions that define a drug's residence time, its distribution and metabolization 1–5. Within this context, 3‐D cell culture designs aim to closer model the in vivo cellular environment characterized by multilayered cell structures in the xyz directions and an extracellular matrix that provides a scaffolding structure the cells interact with.…”

Mimicking the biological world: Methods for the 3D structuring of artificial cellular environments

“…The integration of microsystem technology and biological research has accelerated developments in stem cell research and tissue engineering and is additionally promising the decrease of laboratory-animal use for experimentation [8,15,33,63]. Although current approaches in 3D cell culturing have not reached the level of standard applications, it is widely accepted that miniaturized bioreactors better reflect in vivo environments as they can more accurately represent diffusion gradients across tissues and cellular interactions [64].…”

“…Various bioreactors that have been published differ not only in their dimensions and their seeding capacity for cells [15,24,25], but also in the material they are made of, medium supply, cultivation period, and peripheral equipment, such as connectors, integration of perfusion, sensors, and potential automation [66]. Various bioreactors that have been published differ not only in their dimensions and their seeding capacity for cells [15,24,25], but also in the material they are made of, medium supply, cultivation period, and peripheral equipment, such as connectors, integration of perfusion, sensors, and potential automation [66].…”

“…The resulting 3D structures, normally made of ceramic or polymer (preferably modified synthetic polymer or natural polymer) are then seeded with cells for cultivation [4,[15][16][17]. The resulting 3D structures, normally made of ceramic or polymer (preferably modified synthetic polymer or natural polymer) are then seeded with cells for cultivation [4,[15][16][17].…”