טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentGinini Jiriys George
SubjectDistraction Osteogenesis under Extracorporeal Shock Wave
Therapy (ESWT) - The Bone Biology Effects in the
Rat Mandible
DepartmentDepartment of Medicine
Supervisors Clinical Professor Adi Rachmiel
Dr. Gila Maor


Abstract

Distraction osteogenesis (DO) is an active process of bone regeneration under controlled mechanical stimulation. Distraction osteogenesis has gained widespread clinical use in the craniofacial field for the treatment of congenital and acquired deformities. Nonetheless, its major drawback is its prolonged consolidation period, in which the vulnerable newly regenerated bone is exposed to numerous factors and may carry the risk of increased complications. Several methods, biophysical and biochemical, have been introduced to shorten the consolidation period and enhance bone healing, thereby reducing the costs, complications and burden on the patient. One of these methods is extracorporeal shock wave therapy (ESWT), which generates acoustic waves, transferred through tissues. This mechanical stimulation is translated into a biological effect. In the field of orthopedics, ESWT has been shown to induce neovascularization and promote tissue regeneration by upregulation of several osteogenesis growth factors and proliferating factors that stimulate differentiation of mesenchymal cells into osteogenic lineage for enhanced bone regeneration. Although ESWT is extensively used in healing long bone fractures and musculoskeletal disorders, it has not yet been sufficiently investigated in craniofacial bone healing processes and specifically in DO.

The aims of our study are to investigate whether extracorporeal shock wave therapy can accelerate bony consolidation and regeneration in distraction osteogenesis of the rat mandible. Second, at which stage of distraction osteogenesis EWST is most effective to accelerate bone consolidation and regeneration.

27 male Sprague Dawley rats were subjected to DO of the right mandible (latency period, 3 days; distraction period, 10 days at a rate of 0.5 mm/day). Rats were divided to three groups: group I (control) without ESWT, group II received ESWT (0.18 mJ/mm2) at latency period and group III received ESWT (0.18 mJ/mm2) at consolidation period. Three animals did not survive the experiment and were excluded, one from each group. 24 animals were sacrificed after 4 weeks of consolidation period and explants were removed for radiographic, histological, collagen orientation, micro-CT and immunohistochemical (IHC) evaluation.

Radiographic X-ray showed more radiopacity in both ESWT treatment groups compared with control. Histological evaluation detected intense capillary formation, osteocytes within the mature bone, and bone remodeling compared to other groups. The collagen orientation index showed more lamellar bone in group III, as opposed to control group which exhibited more woven bone. μCT of the distracted mandible showed significantly increased bone mineral density, bone volume fraction and trabecular thickness in group III compared to control group (P<0.05). Immunohistochemistry demonstrated significantly increased expression of Bone Morphogenetic Protein-2, Vascular Endothelial Growth Factor, osteocalcin and collagen type-1 proteins in group III compared to control group.

The present study demonstrated that ESWT application at consolidation period during DO in rat mandible enhances bone formation, extracellular bone matrix protein, osteogenic and angiogenic growth factors, improves bone mechanical properties and accelerates bone mineralization.