Bioreactor Systems for Bone Tissue Engineering

Abstract

Bone graft material is often required for the treatment of osseous defects. However, due to limitations and risks associated with autologous as well as allogenic bone grafting procedures, alternative strategies are needed. In this context, ex vivo tissue engineering (TE) strategies for de novo generation of bone tissue include the combined use of autologous bone-forming cells and three-dimensional (3D) porous scaffold materials serving as structural support for the cells. Three-dimensional cultivation of osteoprogenitor cells presents several challenges, for example, insufficient nutrient and oxygen transport to and removal of waste products from the cells at the interior of the scaffold. By providing physical stimulation of tissue-engineered constructs and resolving mass transport limitations bioreactor systems denote key components for bone TE strategies. A variety of dynamic 3D bioreactor concepts mimicking the native microenvironment in bone tissue, for example, spinner flasks, rotating wall vessel constructs, perfusion bioreactors, and systems based on mechanical or electromagnetic stimulation of cell/scaffold composites, have been developed. These techniques differ considerably with respect to ease of use, cost-effectiveness, and degree of additional osteogenic stimuli, as well as monitoring and manipulation options. This review provides an overview of the concepts, advantages, challenges, and potential future applications associated with current bioreactor systems for bone TE.

The Potential Impact of Bone Tissue Engineering in the Clinic

“…Three types of bioreactors may be used for BTE. They are: rotating wall, spinner flask and flow perfusion, among which, flow perfusion bioreactors have been found most suitable due to uniform cell seeding and the media flow coming in direct contact with the cell-seeded biomaterials causing predictable shear stress to the cells [15,[100][101]105].…”

“…Co-culture of MSCs along with endothelial cells in a hydrogel such as fibrin can also lead to the formation of vessel-like structures in what has been termed a 'prevascularized' tissue-engineered bone graft [105,106]. One difficulty for cell-seeded solid-cured polymer, ceramic or composite scaffolds or hydrogel scaffolds to gain entry in the clinic is that there is little experience with them in the clinic.…”

Will Regenerative Medicine Replace Transplantation?

“…Bioreactors are devices that facilitate, monitor, and control biological, biochemical, and biophysical processes, and allow uniform scaffold cell distribution, ideal nutrient supply and waste removal, as well as hydrodynamic shear stress (Baiguera et al 2010;Rauh et al 2011). Shear stress is produced by forces inherent to the bioreactor-like rotation and other factors essential for tissue development, because it contributes to supporting metabolic activity and differentiation.…”

The influence of hydrostatic pressure on tissue engineered bone development

“…The use of a bioreactor enables precise control of the biophysical and biochemical environment experienced by the construct during growth (Rauh et al, 2011;El Haj and Cartmell, 2010;Yeatts and Fisher, 2011). Cells respond to both biomechanical and biochemical cues and thus need to be subjected to the correct mechanical and biochemical environment to function appropriately (El Haj et al, 2005).…”