Mechanical stimulus has been identified for a long time as a key player in the adaptation of the musculo-skeletal tissues to their function. Mechanical loading is then an intrinsic variable to be considered when new developments are proposed in bone tissue engineering. By combining structural biomechanics and mechanotransduction aspects, a new paradigm is presented for bone tissue engineering. It is proposed that in vivo mechanical loading be used to increased bone formation in the scaffold instead of pre-seeding the scaffold with cells or delivering growth factors. In this article, we demonstrated the feasibility of this approach and compared it to the classical tissue engineering strategy. In particular, we showed that bone formation could be increased in the scaffold that underwent mechanical loading during an in vivo study in rats. A model of bone formation was then proposed to translate the in vivo results into a possible clinical application where the loading of the scaffold would be transmitted by the sharing of the load between an implant and the bone scaffold.