Towards Self-Regulated Bioprocessing: A Compact Benchtop Bioreactor System for Monitored and Controlled 3D Cell and Tissue Culture.

Abstract

Bioreactors are crucial tools for the manufacturing of living cell-based tissue engineered products. However, to reach the market successfully, higher degrees of automation, as well as a decreased footprint still need to be reached. In this study, the use of a benchtop bioreactor for in vitro perfusion culture of scaffold-based tissue engineering constructs is assessed. A low-footprint benchtop bioreactor system is designed, comprising a single-use fluidic components and a bioreactor housing. The bioreactor is operated using an in-house developed program and the culture environment is monitored by specifically designed sensor ports. A gas-exchange module is incorporated allowing for heat and mass transfers. Titanium-based scaffolds are seeded with human periosteum-derived cells and cultured up to 3 weeks. The benchtop bioreactor constructs are compared to benchmark perfusion systems. Live/Dead stainings, DNA quantifications, glucose consumption, and lactate production assays confirm that the constructs cultured in the benchtop bioreactor grew similarly to the benchmark systems. Manual regulation of the system set points enabled efficient alteration of the culture environment in terms of temperature, pH, and dissolved oxygen. This study provides the necessary basis for the development of low-footprint, automated, benchtop perfusion bioreactors and enables the implementation of active environment control.