Solaf Abdulqadir Mustafa

Critical-sized bone defects represent a major clinical challenge, as defects of this magnitude do not heal spontaneously without regenerative intervention. This study aimed to evaluate the osteoinductive effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded β-tricalcium phosphate (β-TCP) scaffolds on bone regeneration and vascularization in a rabbit calvarial critical-sized defect model. Eighteen male New Zealand White rabbits were used, and four standardized circular defects (5 mm in diameter) were created in the calvaria of each animal. The defects were assigned to four groups: control (unfilled), β-TCP + 5 µg rhBMP-2, β-TCP + 10 µg rhBMP-2, and β-TCP + 20 µg rhBMP-2. Bone healing was evaluated at 2, 4, and 8 weeks using histological, histomorphometric, and cluster of differentiation 31 (CD31) immunohistochemical analyses. The results demonstrated that rhBMP-2–loaded β-TCP scaffolds significantly enhanced bone regeneration compared with the control group, with a progressive increase in bone formation observed with increasing rhBMP-2 doses. The β-TCP + 20 µg rhBMP-2 group exhibited the highest levels of new bone formation, more advanced bone maturation, improved collagen organization, and increased vascularization. However, no statistically significant differences were observed between the 10 µg and 20 µg groups at later time points (p > 0.05), suggesting a dose-dependent saturation (plateau) effect. In conclusion, rhBMP-2–loaded β-TCP scaffolds promote bone regeneration and angiogenesis in a dose-related manner up to a threshold, beyond which additional increases in dose do not result in proportional improvements. These findings emphasize that optimal rhBMP-2 dosing is critical to maximize regenerative outcomes while avoiding unnecessary dose escalation.

Critical-sized bone defects represent a major clinical challenge, as bone gaps of this magnitude are unable to heal spontaneously without regenerative intervention. The present study aimed to evaluate the dose-dependent osteoinductive effect of rhBMP-2–loaded β-TCP scaffolds on bone regeneration in critical-sized calvarial defects in a rabbit model. Eighteen adult male New Zealand White rabbits were used, and four circular defects (5 mm in diameter) were surgically created in the calvaria of each animal, resulting in a total of 72 defects. The animals were divided into four groups: control, β-TCP + 5 μg rhBMP-2, β-TCP + 10 μg rhBMP-2, and β-TCP + 20 μg rhBMP-2. Bone healing was evaluated at 2, 4, and 8 weeks postoperatively using histological and histomorphometric analyses. Masson’s trichrome staining was performed to assess collagen deposition and maturation, while CD31 immunohistochemical staining was used to evaluate vascularization. The results demonstrated rhBMP-2–loaded β-TCP scaffolds significantly enhanced bone regeneration in a dose-dependent manner, with the β-TCP + 20 μg rhBMP-2 group demonstrating the greatest new bone formation and more mature bone architecture. In addition, BMP-2 treatment promoted osteoblastic activity, improved collagen maturation, and increased vascularization within the defect area. These findings indicate that rhBMP-2–loaded β-TCP scaffolds enhance bone regeneration in a dose-dependent manner, with higher rhBMP-2 doses resulting in greater bone formation and more mature bone architecture.