TY - JOUR A1 - Ono, Mitsuaki A1 - Sonoyama, Wataru A1 - Nema, Kazuki A1 - Hara, Emilio Satoshi A1 - Oida, Yasutaka A1 - Pham, Hai Thanh A1 - Yamamoto, Katushi A1 - Hirota, Kazuo A1 - Sugama, Kazushige A1 - Sebald, Walter A1 - Kuboki, Takuo T1 - Regeneration of calvarial defects with Escherichia coli-derived rhBMP-2 adsorbed in PLGA membrane JF - Cells Tissues Organs N2 - 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. KW - Escherichia coli-derived recombinant human bone morphogenetic protein-2 KW - Bone regeneration KW - Polylactide-co-glycolide KW - Ectopic bone formation Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196680 SN - 1422-6405 SN - 1422-6421 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 198 IS - 5 SP - 367 EP - 376 ER -