Tissue Engineering

In vitro, epithelial cells and chondrocytes became deeply embedded within the matrix by 24 h. This finding suggests that the matrix is highly permissive and an ideal immediate environment for these cells. In fact, after 24 h in the bioreactor, no cells (alive or dead) could be detected in the culture medium, suggesting a near 100% adherence. The presence of clearly viable epithelial cells and chondrocytes on the graft surface at 4 days confirms this view, and shows that the cells continue to function in vivo.

Bioreactor technology is vital for tissue engineering. Usually, bioreactors are used to provide a tissue-specific physiological in vitro environment during tissue maturation. In addition to this most obvious application, bioreactors have the potential to improve the efficiency of the overall tissue engineering concept. To date, a variety of bioreactor systems for tissue-specific applications have been developed. Of these, some systems are already commercially available. With bioreactor technology, various functional tissues of different types were generated and cultured in vitro.

According to the paradigm of TE, tissue generation includes several single process steps, beginning with the isolation of cells from a biopsy, the expansion of cells in vitro, the generation and maturation of a 3D construct, and subsequently, the use of the construct as a test system or graft. Within this process, there are different prospects for the bioreactor system to improve the robustness, reliability, and efficiency of a certain process step or the whole TE cycle.

A rational design of dynamic culture protocols, intended to actively modulate the growth of engineered tissues, will be conditional on gaining a more comprehensive insight into fundamental cell functions and tissue-development mechanisms. Bioreactors, representing 3D culture-model systems recapitulating specific aspects of the actual in vivo milieu, in conjunction with mathematical models and appropriate sensor technology, can enable a step forward in this direction. 

Sensing in tissue-culture bioreactors can provide an indispensable means to clarify still unknown aspects of the cellular response in dynamic culture conditions, as well as playing an integral role in the automation and in-process control of tissue manufacturing processes. Monitoring basic parameters such as the partial pressure of O2 and CO2 in the culture medium, or detecting glucose and lactate concentrations, allows quantitative evaluation of cell metabolism, thus supporting/substituting subjective and qualitative conclusions traditionally derived by simply observing the color of the medium. 

References:

P Macchiarini, P Jungebluth, T Go, M A Asnaghi, L E Rees, T A Cogan, A Dodson, J Martorell, S Bellini, P P Parnigotto, S C Dickinson, A P Hollander, S Mantero, M T Conconi, M A Birchall. Clinical transplantation of a tissue-engineered airway. Lancet 2008;372(9655):2023–30.

Hansmann J, Groeber F, Kahlig A, Kleinhans C, Walles H. Bioreactors in tissue engineering – principles, applications and commercial constraints. Biotechnol J 2013; 8(3): 298-307.

Wendt D, Riboldi SA, Cioffi M, Martin I. Potential and bottlenecks of bioreactors in 3D cell culture and tissue manufacturing. Adv Mater 2009; 21(32-33): 3352-67.

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