BACKGROUND: The piezoelectric knife was developed for atraumatic bone surgery utilizing ultrasonic vibrations as an alternative to mechanical instruments in conventional oral surgery. Recently it has been used in surgically facilitated orthodontics with Piezocision™. This technique requires alveolar decortication with the piezoelectric knife that cuts through the cortical bone to reach the medullary space. We hypothesized that Its clinical effectiveness is “depth dependent” hence the need to reach the medullary bone and not rely on a “superficial scratch”. This study tested the hypothesis that the extent of the regional acceleratory phenomenon (RAP) following bone injury is depth dependent by comparing superficial and deep corticotomies on the rat tibia. MATERIAL & METHOD: Twenty-six, 9-10 week male Sprague-Dawley rats, weighing approximately 300g, were used in this study approved by the Boston University Medical Center Institutional Animal Care and Use Committee. The piezoelectric knife (Piezotome 2, Acteon, BSL1 insert) with a fixed D 1 power setting and a 30Hz modulation frequency was used to create a decortication on the tibia of the animal. This procedure was carried out with a 1mm penetration depth on the right tibia (deep corticotomy reaching the medullary space) and 0.5mm penetration depth on the left tibia (shallow corticotomy not reaching the medullary space). Tissue response was analyzed at day 1, 3, 7, 14, and 28 using Hematoxylin/Eosin, Masson trichrome, TRAP and picro sirus red stains. Untreated rats were used as controls. The samples were fixed in 4% formaldehyde and the location of the surgical defect underneath the soft tissue was confirmed using Computed Tomography (CT). RESULTS: The CT image analysis was used to cut the samples with extreme precision in the sagittal plane and prepare the tissues for histological analysis. Hematoxylin & Eosin staining highlighted the following sequence of events: 1) establishment of a fibrin clot and granulation tissue (activation phase) 2) increased osteoclastic activity at the site of decortication (resorption phase) 3) increased osteogenic activity (formation phase). Deep corticotomy sites showed extensive morphological changes for both soft and hard tissues. They were characterized by significant osteoclastic activity at day 7 and intense angiogenesis visible both at the entry and exit of the surgical wound. In contrast, the shallow sites showed none of these findings. The new bone that formed at the deep corticotomy site in the medullary space resorbed by at day 14, while the new that bone formed below the periosteum persisted at day 28. None of these phenomena were observed at the shallow sites, where repair had occurred at day 14 or earlier showing minimal RAP activity. CONCLUSION: The extent of the RAP following bone injury is depth dependent. The deep corticotomy sites showed more dramatic biological responses than the shallow osteotomy sites.