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Cell and Tissue Engineering

6.2 Bioreactor Design and Operation

3 min readLast Updated on July 24, 2024

Bioreactors are crucial in cell and tissue engineering, providing controlled environments for cell growth and tissue formation. From stirred-tank to rotating wall vessels, each type offers unique advantages for specific applications, influencing cell behavior and product quality.

Design parameters like mixing, shear stress, and mass transfer significantly impact cell culture outcomes. Careful control of these factors, along with monitoring of pH, temperature, and nutrient levels, is essential for optimizing cell growth and tissue development in various bioengineering applications.

Bioreactor Types and Design Principles

Types of bioreactors in engineering

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  • Stirred-tank bioreactors employ cylindrical vessels with impellers for mixing fostering suspension culture of cells provides homogeneous environment suitable for large-scale production (CHO cells for antibody production)

  • Perfusion bioreactors utilize continuous flow of fresh media mimics in vivo conditions enables efficient nutrient delivery and waste removal includes hollow fiber fixed bed and fluidized bed types (hepatocyte culture for liver assist devices)

  • Rotating wall vessel bioreactors feature cylindrical vessels rotating around horizontal axis creates low shear stress environment simulates microgravity conditions supports 3D tissue growth (cartilage tissue engineering)

Influence of bioreactor design parameters

  • Mixing ensures uniform distribution of nutrients and cells affects oxygen and pH gradients influences cell aggregation and spheroid formation (embryoid body formation)

  • Shear stress exerts mechanical force on cells by fluid flow impacts cell morphology and alignment regulates gene expression and differentiation excessive shear can cause cell damage (endothelial cell alignment in vascular tissue engineering)

  • Mass transfer facilitates delivery of nutrients and removal of waste products oxygen transfer rate (OTR) critical for aerobic cultures affects cell metabolism and growth kinetics influenced by bioreactor geometry and operating conditions (scale-up of stem cell expansion)

Process Control and Optimization

Monitoring and control of bioreactors

  • pH control maintains optimal range 7.2-7.4 for most mammalian cells uses pH probes or sensors regulated by CO2 sparging or addition of base/acid (fibroblast culture)

  • Temperature regulation typically set at 37℃ for mammalian cells employs thermocouples or resistance temperature detectors (RTDs) controlled by heating jackets or immersion heaters (T-cell expansion)

  • Dissolved oxygen (DO) management aims for 20-50% of air saturation for most cell types uses polarographic or optical DO sensors controlled by air or oxygen sparging agitation speed adjustment (cardiomyocyte differentiation)

  • Nutrient concentration monitoring utilizes online sensors for glucose glutamine and lactate offline sampling and analysis for other metabolites feed strategies based on nutrient consumption rates (fed-batch culture of hybridomas)

  • Cell density and viability assessment employs online methods like capacitance probes optical density sensors offline methods include cell counting flow cytometry (mesenchymal stem cell expansion)

Scalability of bioreactor-based production

  • Scalability considerations address surface area to volume ratio changes oxygen transfer limitations shear stress variations nutrient gradients in larger vessels (scale-up of vaccine production)

  • Economic factors encompass capital costs (equipment facility installation) operating costs (media labor energy maintenance) product yield and quality at different scales regulatory compliance and validation expenses (CAR-T cell therapy production)

  • Applications in regenerative medicine compare autologous vs allogeneic cell therapies develop tissue-engineered products (skin cartilage) face challenges in maintaining product consistency at larger scales (bone tissue engineering)

  • Drug screening applications utilize high-throughput 3D tissue models organ-on-a-chip systems evaluate cost-effectiveness compared to animal models (liver toxicity screening)

  • Process optimization strategies implement design of experiments (DOE) for parameter optimization apply process analytical technology (PAT) compare continuous processing vs batch production (optimization of recombinant protein production)

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© 2025 Fiveable Inc. All rights reserved.
AP® and SAT® are trademarks registered by the College Board, which is not affiliated with, and does not endorse this website.

© 2025 Fiveable Inc. All rights reserved.
AP® and SAT® are trademarks registered by the College Board, which is not affiliated with, and does not endorse this website.