Bioreactors application: bone and cartilage

Bone tissue engineering is a promising solution for patients with bone defects that require reconstruction. This regenerative therapy consists in culturing osteogenic cells on a biodegradable substrate to obtain a bio-hybrid construct that will stimulate bone healing after implantation. This multidisciplinary technology nevertheless requires further development before it can become routine clinical practice. One challenge is to achieve three-dimensional seeding and osteogenic commitment of mesenchymal stem cells on biomaterials under sterile and reproducible conditions. For this purpose, different dynamic culture systems have been developed to improve nutrient delivery to the cells and generate shear stress that may promote cell differentiation into osteoblastic phenotypes.

The dynamic culture environment in our bioreactor, controllable and reproducible, is essential for the nutrient supply and waste removal needed to sustain large three-dimensional constructs. The rotation provides the hydrodynamic shear stress necessary to promote metabolic activity and proper differentiation of the seeded cells.

The cartilage regenerative medicine field has evolved during the last decades. The first-generation technology, autologous chondrocyte transplantation (ACT) involved the transplantation of in vitro expanded chondrocytes to cartilage defects. The second generation involves the seeding of chondrocytes in a three-dimensional scaffold. The nutritional requirements of cells that are synthesizing extra-cellular matrix increase along the differentiation process. The mass transfer must be increased according to the tissue properties. Bioreactors represent an attractive tool to accelerate the biochemical and mechanical properties of the engineered tissues providing adequate mass transfer and physical stimuli.

Different bioreactor systems have been developed during the last decades based on different physical stimulation concepts; perfusion systems represent an attractive way of culturing constructs under dynamic conditions. Several groups showed increased matrix production using confined and unconfined systems. Development of automatic culture systems and noninvasive monitoring will take place during the next few years in order to improve the reliability of tissue-engineered products.

Perfusion bioreactor systems have been very effective for the culture of MSCs, being demonstrated to increase proliferation, osteogenesis, and chondrogenesis. These observed results are attributed to the ability of the systems to increase nutrient transport including oxygen and expose the cells to mechanical stimulus. When the effect of these two stimuli was independently evaluated, shear stress and mass transport were each shown to have an effect on human mesenchymal stem cell (hMSC) growth and osteoblastic differentiation.

References:

Carpentier B, Layrolle P, Legallais C. Bioreactors for bone tissue engineering. Int J Artif Organs. 2011 Mar;34(3):259-70.

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.

Concaro S, Gustavson F, Gatenholm P. Bioreactors for tissue engineering of cartilage. Adv Biochem Eng Biotechnol. 2009;112:125-43

Yeatts AB, Choquette DT, Fisher JP. Bioreactors to influence stem cell fate: Augmentation of mesenchymal stem cell signaling pathways via dynamic culture systems. Biochim Biophys Acta 2013; 1830(2): 2470-80.

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