Objective To investigate the repair efficacy of 3D-printed individualized titanium mesh (3D-PITM) combined with guided bone regeneration (GBR) in a rabbit model of osteoradionecrosis of the jaws (ORNJ) with bone defects.Method 18 white rabbits with ORNJ-induced bone defects were randomly divided into three groups: a Group (debridement and suturing for natural healing), b Group(debridement and conventional GBR), and c Group(debridement and 3D-PITM-supported GBR)?. 2 rabbits from each group were euthanized at 4, 8, and 12 weeks for immunohistochemical staining to detect the expression levels of Osteogenesis-related factors alkaline phosphatase (ALP), osteocalcin (OC), and bone morphogenetic protein-2 (BMP-2)?；Inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)evaluating bone defect repair outcomes.Result At 4 weeks, no significant differences in ALP expression were observed among groups, and OC levels in c Group were lower than those in b Group. However, at 8 and 12 weeks, ALP, BMP-2, and OC expression levels in c Group were significantly higher than those in a and b Groups?. At 4,8 and 12 weeks, the expression levels of IL-6 and TNF-α in c group were significantly lower than those in a and b groups. However, at 4 weeks, no statistically significant difference in IL-6 expression was observed between c and b groups.Conclusion The combination of 3D-PITM and GBR demonstrated significantly superior bone defect repair efficacy in ORNJ compared to conventional GBR or natural healing alone.