Investigation of the effect of liraglutide use on healing of different graft types in critical size calvarial defects in rats

Objective: Bone graft materials are frequently employed in the treatment of critical sized bone defects, and pharmacological agents that can enhance their regenerative efficacy have gained increasing interest. This study aimed to investigate the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist Liraglutide (LIRA) on bone regeneration when combined with different graft materials. Method: Bilateral critical-sized calvarial defects (5 mm in diameter) were surgically created in 6–8-week-old male Wistar rats. Eight experimental groups were established: control, autograft, allograft, xenograft, and their respective counterparts treated with LIRA. LIRA was administered subcutaneously at a dose of 0.3 mg/kg/day throughout the 8-week healing period. Following euthanasia, samples were analyzed using histomorphometry, micro-computed tomography (micro-CT), and immunohistochemistry targeting β-catenin, BMP-2, osterix, osteoprotegerin, RANKL, and RUNX2. Results: Histomorphometric data demonstrated that LIRA significantly enhanced the osteogenic performance of the grafts (p<0.05). The LIRA+autograft group showed the highest levels of new bone formation and defect closure. Immunohistochemical results revealed that LIRA promoted osteoblastic activity while suppressing osteoclastic activity. Micro-CT findings supported these outcomes, indicating significant improvements in bone volume, trabecular thickness, and structural integrity. Conclusion: LIRA was found to enhance bone healing and exert a synergistic effect when used in combination with bone grafts. These findings suggest that LIRA may serve as a promising adjunct in bone tissue engineering and regenerative medicine. Keywords: Allograft, calvarial defect, xenograft, liraglutide, autogenous graft, rat