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; Livia      Visai

Abstract

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