title: *Demineralized Bone Matrix as a Carrier for Bone Morphogenetic Protein-2: Burst Release Combined with Long-Term Binding and Osteoinductive Activity Evaluated In Vitro and In Vivo.
abstract: To allow bone defect regeneration, autologous bone grafting still represents the gold standard. However, autograft harvesting has limitations, including an additional surgery, donor site morbidity, and limited availability. Demineralized bone matrix (DBM) would represent an alternative, yet lacks sufficient osteoinductive properties. Combining DBM with a potent agent, such as bone morphogenetic protein-2 (BMP-2) might be a feasible alternative approach, optimizing an established grafting material with strong osteoinductive properties. A unique mixing device has been developed that enables perioperative handling to reach a homogeneous and standardized paste for bone defect filling. DBM proved in vitro to be a suitable carrier for BMP-2, with a documented release over 56 days at concentrations sufficient to stimulate osteogenic differentiation. At the end of the elution experiment, 56 days, bioactive BMP was still captured within the DBM. Using a sheep drill hole defect model, DBM perioperatively mixed with BMP-2 showed strong osteoinductive properties comparable to those of autologous bone and outnumbering the one of DBM alone or empty defects. Bone defect healing was enabled at diaphyseal and metaphyseal defects and thus BMP-2-doped DBM represented an easy perioperative enriching method and an efficient carrier for BMP-2. With the comparability to the clinical gold standard autologous bone, DBM mixed with BMP-2 might serve as possible alternative grafting material enabling a controlled osteogenic stimulation.
authors.affiliation: 1 Julius Wolff Institut, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Huber
authors.affiliation: 1 Julius Wolff Institut, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Pobloth
authors.affiliation: 1 Julius Wolff Institut, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Nicole
authors.initials: N
authors.lastname: Bormann
authors.affiliation: 1 Julius Wolff Institut, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Nicolai
authors.initials: N
authors.lastname: Kolarczik
authors.affiliation: 1 Julius Wolff Institut, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmidt-Bleek
authors.affiliation: 1 Julius Wolff Institut, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Hanna
authors.initials: H
authors.lastname: Schell
authors.affiliation: 3 Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Philipp
authors.initials: P
authors.lastname: Schwabe
authors.affiliation: 1 Julius Wolff Institut, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.affiliation: 1 Julius Wolff Institut, Charité-Universitätsmedizin Berlin , Berlin, Germany .|2 Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Berlin, Germany .
authors.forename: Britt
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000737:chemistry*; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects*; D012756:Sheep
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations
keywords: BMP-2; DBM; autologous bone graft; defect healing; perioperative mixing; release kinetics