BACKGROUND: Bone decortication is essential to activate bone based on the Regional Acceleratory Phenomenon (RAP), a post-injury transient bone remodeling phenomenon. The Piezoelectric knife with low ultrasonic frequency has been shown to cut bone with minimal invasive effect on soft tissues, less inflammatory response compared to conventional Bur that causes trauma leading to excessive inflammation. Previous studies have shown that using graft materials for Guided Bone Regeneration (GBR) had a significant beneficial effect on the healing process and the thickness of new bone formation. This study hypothesized that the piezoelectric knife would create a better tissue response to different graft materials compared to conventional carbide bur with grafts or the graft alone. MATERIAL & METHOD: Eighteen 9-10 week male Sprague-Dawley rats (300-350g) were purchased from Charles River Laboratories. This study was approved by Boston Medical Center Institutional Animal Care and Use Committee. The piezoelectric knife (BS1 insert) of the Piezotome 2 (Acteon) was used for deep decortication and compared to a conventional carbide osteotomy bur (#1/2) with Mucograft (Geistlich) or OsteoGen (Impladent, Ltd) graft materials, Onlay graft material alone served as a control. Digital dentistry using Cone Beam Computed Tomography (CBCT) located and allowed precise cut of the area of interest without detached the surrounding soft tissue. Tissues collected from day 7 and day 28 were sectioned and stained with Hematoxylin/Eosin or Masson trichome stains. RESULTS: The Cone Beam Computed Tomography (CBCT) scans significantly increased the success rate in locating and cutting the area of interest. Hematoxylin & Eosin staining showed on day 7 that piezoelectric knife activated a broad bone response and less inflammatory response. While recruiting and enlarging chondrocytes to the Mucograft area which will turn to new bone. The use of OsteoGen combined with a piezoelectric knife resulted in thickening in the cortical bone around and above the defect area. CONCLUSION: Piezoelectric knife with Mucograft healed faster compared to bur or graft alone. The piezoelectric knife resulted in significantly increased bone thickness when combined with OsteoGen.