Bioreactor systems for bone tissue engineering

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.