Immediate versus delayed application of bone morphogenetic protein-2 solution in damaged extraction sockets: a preclinical in vivo investigation

Objective: To compare the clinical, radiographic, and histological healing patterns between the immediate and delayed applications of bone morphogenetic protein-2 (BMP-2) in damaged extraction sockets in dogs. Materials and methods: The distal roots of the fourth premolars of the mandible were extracted bilaterally in five beagle dogs, and buccal bone defects (4 mm wide and 9 mm high) were surgically created. Collagenated biphasic calcium phosphate (CBCP) soaked for 10 min in 100 μL of BMP-2 solution was applied immediately to the defect site in the control group. In the test group, the BMP-2 solution of same dose was injected into the grafted site 2 weeks after grafting with a saline-soaked CBCP. The dogs were sacrificed 2 weeks later. Clinical, histological, and radiographic analyses were followed. Results: Swelling and inflammatory reactions were predominantly observed in the control group at 2 weeks. The area of new bone formation was significantly larger in the control group compared with the test group (10.8 ± 7.0 mm2 [mean ± SD] and 6.3 ± 3.1 mm2, respectively; p = 0.043). No significant difference was found in ridge width at 2 mm, 4 mm and 6 mm below the lingual bone crest between the control (2.6 ± 1.0 mm, 3.2 ± 0.9 mm and 4.5 ± 0.5 mm, respectively) and test group (3.3 ± 1.0 mm, 3.7 ± 1.3 mm and 4.2 ± 1.0 mm; all p > 0.05). Conclusions: Delayed application of BMP-2 2 weeks after surgery did not show any advantage over immediate application of BMP-2 in terms of new bone formation. Clinical relevance: This study suggests that it might be better to apply BMP-2 immediately in alveolar ridge preservation, instead of delayed application, in order to enhance new bone formation. Keywords: Alveolar ridge augmentation; Animal experimentation; Bone morphogenetic protein 2; Bone substitutes; Damaged extraction socket; Extraction socket regeneration; Tooth extraction