In Vitro Osteogenesis of Human Stem Cells by Using a Three-Dimensional Perfusion Bioreactor Culture System: A Review
Gabriele Ceccarelli, Nora Bloise, Marco Vercellino, Rosalia Battaglia, Lucia Morgante, Maria Gabriella Cusella De Angelis, Marcello Imbriani and Livia Visai
Affiliation: Dep. of Molecular Medicine, University of Pavia, Viale Taramelli 3/B, 27100 Pavia, Italy.
Tissue engineering (by culturing cells on appropriate scaffolds, and using bioreactors to drive the correct bone
structure formation) is an attractive alternative to bone grafting or implantation of bone substitutes. Osteogenesis is a biological
process that involves many molecular intracellular pathways organized to optimize bone modeling. The use of
bioreactor systems and especially the perfusion bioreactor, provides both the technological means to reveal fundamental
mechanisms of cell function in a 3D environment, and the potential to improve the quality of engineered tissues. In this
mini-review all the characteristics for the production of an appropriate bone construct are analyzed: the stem cell source,
scaffolds useful for the seeding of pre-osteoblastic cells and the effects of fluid flow on differentiation and proliferation of
bone precursor cells. By automating and standardizing tissue manufacture in controlled closed systems, engineered tissues
may reduce the gap between the process of bone formation in vitro and subsequent graft of bone substitutes in vivo.
Keywords: Biomaterials, extracellular matrix, induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSC), osteogenesis,
perfusion bioreactor, scaffolds, tissue engineering
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