: Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodeling throughout adult life. Biphasic calcium phosphate is the most frequently used synthetic bone substitutes, which comprises a combination of hydroxyapatite and beta-tricalcium phosphate. It is are now considered the new gold standard in bone grafting and bone reconstructive surgery.Hyaluronic acid exists naturally as an important component of the extracellular matrix in the human body. It has been studied as a biomaterial for tissue engineering. Bone sialoprotein is an acidic, non-collagenous glycoprotein abundantly expressed in mineralized tissues. Bone morphogenetic protein- 4 is one of the growth and differentiation factors that is highly upregulated in the early stages around the injured periosteum. The aim of this study was to evaluate the effect of Hyaluronic acid, hydroxyapatite / beta tricalcium phosphate (HA\β-TCP) and their combination on bone healing by means of histological, histomorphometrical analysis and Immunohistochemical expression of bone sialoprotein and bone morphogenetic protein-4