Bone regeneration following the in vivo bioreactor principle: is in vitro manipulation of exogenous elements still needed?

Large bone defect treatment is a key challenge due to the difficulty of functional and aesthetic reconstruction. A promising approach for bone regeneration is bone tissue engineering which is based on in vitro manipulation of seed cells, growth factors and bioscaffolds. However, many formidable conceptual and technical challenges impede clinical translation of experimental successes into clinical practices. An emerging strategy for bone regeneration is using the body as a bioreactor to cultivate the traditional triad and leveraging the body's own regenerative capacity to create new bone tissue. Based on the understanding of bone regeneration and in vivo bioreactor principle, we hypothesize that functional bone tissue may be eventually generated in vivo only using autologous costal periosteum, without participation of any exogenous elements.