title: Endocultivation: continuous application of rhBMP-2 via mini-osmotic pumps to induce bone formation at extraskeletal sites.
abstract: The continuous presence of recombinant human bone morphogenetic protein 2 (rhBMP-2) inside a scaffold may be crucial to the outcome in bone tissue engineering. This study investigated whether the release of the growth factor rhBMP-2 via different continuous application schemes influences histomorphological aspects of the hard and soft tissues induced. Three-dimensionally printed hydroxyapatite scaffolds were implanted into one latissimus dorsi muscle of 42 female Lewis rats. Simultaneously implanted mini-osmotic pumps were used to provide a continuous application of rhBMP-2 over 1, 2, or 4 weeks (total dose 200μg). A reference group received rhBMP-2 at the time of implantation only, and a control group received only block implantation. Bone density and histological examinations were performed after 8 weeks. No significant difference in bone density was found between the groups; however, the blood vessel count differed significantly between the groups receiving continuous treatments and both the control group and simultaneous rhBMP-2 treatment group (P<0.0001). Soft tissue types were distributed differently among the study groups. RhBMP-2 application via mini-osmotic pumps is as suitable for inducing bone formation as a single application at the time of implantation. The time interval over which rhBMP-2 was administered had no impact on the amount of new bone formation, probably due to the study duration and low local concentrations of growth factor.
authors.affiliation: Medical University Centre Hamburg-Eppendorf, Department of Oral and Maxillofacial Surgery, Hamburg, Germany. Electronic address: b.beck-broichsitter@uke.de.
authors.forename: B E
authors.initials: BE
authors.lastname: Beck-Broichsitter
authors.affiliation: Department of Oral and Maxillofacial Surgery, Schleswig-Holstein University Hospital, Kiel, Germany.
authors.forename: S T
authors.initials: ST
authors.lastname: Becker
authors.affiliation: Fluid Technology and Microfluidics, University of Rostock, Rostock, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Seitz
authors.affiliation: Department of Oral and Maxillofacial Surgery, Schleswig-Holstein University Hospital, Kiel, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Schleswig-Holstein University Hospital, Kiel, Germany.
authors.forename: P H
authors.initials: PH
authors.lastname: Warnke
mesh_terms: D000818:Animals; D001682:Biological Availability; D015519:Bone Density; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D016503:Drug Delivery Systems; D017886:Durapatite / Q000494:pharmacology; D005260:Female; D023421:Models, Animal; D009995:Osmosis; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D017886:Durapatite
keywords: bone density; endocultivation; heterotopic bone induction; rhBMP-2; soft tissue