Ultrasound for bone tissue engineering and regenerative medicine

We will review the role of ultrasound in bone tissue engineering and regenerative medicine, for enhancement of fracture healing and reactivation of a failed healing process. These approaches rely typically either on the direct stimulation of the healing process or in the delivery at the injury site of scaffold-embedded biologics such as cells, signaling molecules, and genetic material. Different options are available for ultrasound enhancement of fracture healing such as low intensity pulsed ultrasound (LIPUS) and shock waves, for the delivery of regenerative factors and encoding genes, and for the assembly and patterning of scaffolds. A main emphasis will be put on LIPUS-related bioeffects, the most widespread and studied technique. Pronounced bioeffects on tissue regeneration have been reported employing intensities within a diagnostic range. We will describe the current knowledge of the biological response to LIPUS, involving numerous cell types and molecular pathways, hypothesis about LIPUS biophysics...