Several preclinical studies have shown that Escherichia coli-derived bone morphogenetic protein-2 (E-BMP-2) is as effective as mammalian cell-derived bone morphogenetic protein-2 (C-BMP-2) in the treatment of bone defects. However, further investigation of the effectiveness and determination of the optimal dosage of E-BMP-2 in large animals are still necessary before its full application in humans. This study investigated the efficiency of different concentrations of E-BMP-2 adsorbed in β-TCP for bone augmentation and osseointegration of immediate dental implants in a swine socket lift model. Following exposure of the maxillary sinus lateral wall, a 3.4-mm (diameter) cavity was drilled and filled with 0.1 g of β-TCP containing different doses of E-BMP-2 (0, 10, 30, or 100 μg/site) to lift the Schneiderian membrane. A dental implant was then immediately inserted. Bone-to-implant contact (BIC) and bone density (BD) examined via histological analysis were used as parameters to assess E-BMP-2 efficiency in bone formation. The implant stability quotient (ISQ) was measured using Osstell to determine the effect of E-BMP-2/β-TCP on implant stability. After 8 weeks, the groups that received 30 and 100 μg of E-BMP-2 showed substantial new bone formation in the elevated space, while no bone formation was observed with β-TCP alone. Accordingly, BIC and BD presented a dose-dependent response to increasing doses of E-BMP-2. However, there was no increase in implant stability with E-BMP-2 treatment. In conclusion, the E-BMP-2/β-TCP combination was efficient in bone formation and osseointegration of dental implants in a socket lift model in mini-pigs.

Objective:Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) has been shown to be as effective as mammalian cell-derived BMP-2. However, several in vitro and in vivo experiments are still necessary to validate the effectiveness of E-BMP-2 due to the difference in synthesis process, mainly related to protein nonglycosylation. The objective of this study was to investigate whether biodegradable polylactide-co-glycolide (PLGA) membrane is a suitable carrier for E-BMP-2 delivery for bone regeneration of critical-sized defects in rat calvaria. Materials and Methods: First, the osteoinductive effect of E-BMP-2 was confirmed in vitro in mouse bone marrow stromal cells by analysis of osteocalcin mRNA levels, and calcium deposition was detected by alizarin red staining. Before in vivo experiments, the release profile of E-BMP-2 from PLGA membranes was determined by ELISA. E-BMP-2 (0, 1, 5 and 10 μg/μl) was applied for ectopic and orthotopic bone formation and was analyzed by X-ray, micro-CT and histology. Results: Release-profile testing showed that PLGA membrane could retain 94% of the initially applied E-BMP-2. Ectopic bone formation assay revealed that combination of E-BMP-2/PLGA membrane strongly induced bone formation. Stronger osteoinductivity with complete repair of critical-sized defects was observed only with PLGA membranes adsorbed with 5 and 10 μg/μl of E-BMP-2, whereas no bone formation was observed in the groups that received no membrane or 0-μg/μl dose of E-BMP-2. Conclusion: PLGA membrane was shown to be a suitable carrier for sustained release of E-BMP-2, and the E-BMP-2/PLGA membrane combination was demonstrated to be efficient in bone regeneration in a model of critical-sized defects.