Abstract
Techniques to provide in vitro tissue culture have undergone significant changes during the last decades, and current applications involve interactions of cells and organoids, three-dimensional cell co-cultures, and organ/body-on-chip tools. Efficient computer-aided and mathematical model-based methods are required for efficient and knowledge-driven characterization, optimization, and routine manufacturing of tissue culture systems. As an alternative to purely experimental-driven research, the usage of comprehensive mathematical models as a virtual in silico representation of the tissue culture, namely a digital twin, can be advantageous. Digital twins include the mechanistic of the biological system in the form of diverse mathematical models, which describe the interaction between tissue culture techniques and cell growth, metabolism, and the quality of the tissue. In this review, current concepts, expectations, and the state of the art of digital twins for tissue culture concepts will be highlighted. In general, DT’s can be applied along the full process chain and along the product life cycle. Due to the complexity, the focus of this review will be especially on the design, characterization, and operation of the tissue culture techniques.
Highlights
Tissue culture refers to a micro-structured cell culture under in vitro conditions that take into account the three-dimensionality (3D) and the physiology of the tissue
Because these systems are capable of supporting culture of large 3D cell agglomerates, but hardly mimic the in vivo microenvironment, numerous culture systems are designed especially for tissue engineering mimicking the special demands of a three-dimensional tissue have been developed
The concepts, expectations, and the state of the art of Digital Twins (DT) were reviewed for tissue culture techniques with a special focus on their design, characterization, and operation
Summary
Tissue culture refers to a micro-structured cell culture under in vitro conditions that take into account the three-dimensionality (3D) and the physiology of the tissue. While DT-based concepts for production of biopharmaceuticals are already being used in industrial practice or tested by pharmaceutical companies for the development, optimization, and operation of production systems for biopharmaceuticals (recently reviewed in [12,13]), there are so far only a few DT-approaches, mostly for the generation of implantable tissues as Advanced Therapy Medical Products (ATMPs) or tissue-specific test systems for new pharmaceutics or toxicity tests [5,6,14,15,16,17,18,19]. Conclusions will be drawn concerning the state of the art and future expectation for digital twins for tissue culture concepts
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