title: The effect of SDF-1α on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model.
abstract: The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1α) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1α and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1α group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2 + SDF-1α group (5.8 ± 0.6 mm³, p = 0.0479) and the high dose BMP-2 group (6.5 ± 0.7 mm³, p = 0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 ± 0.5 mm³). There was a higher healing score in the low dose BMP-2 + SDF-1α group (median grade 8; Q1-Q3 7-9; p = 0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1α from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1α seems to enhance the osteoinductive potential of BMP-2. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016.
authors.affiliation: Center for Orthopaedics and Traumatology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.|Center for Translational Bone, Joint, and Soft Tissue Research, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zwingenberger
authors.affiliation: Center for Orthopaedics and Traumatology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.|Center for Translational Bone, Joint, and Soft Tissue Research, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Langanke
authors.affiliation: Center for Translational Bone, Joint, and Soft Tissue Research, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Corina
authors.initials: C
authors.lastname: Vater
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, England.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Lee
authors.affiliation: Center for Orthopaedics and Traumatology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.|Center for Translational Bone, Joint, and Soft Tissue Research, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Eik
authors.initials: E
authors.lastname: Niederlohmann
authors.affiliation: Center for Orthopaedics and Traumatology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Sensenschmidt
authors.affiliation: Center for Translational Bone, Joint, and Soft Tissue Research, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Jacobi
authors.affiliation: Institute for Materials Science and Max Bergmann Center for Biomaterials, Technische Universität Dresden, Dresden, Germany.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bernhardt
authors.affiliation: Institute of Pathology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Muders
authors.affiliation: Center for Orthopaedics and Traumatology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rammelt
authors.affiliation: Center for Translational Bone, Joint, and Soft Tissue Research, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Knaack
authors.affiliation: Center for Translational Bone, Joint, and Soft Tissue Research, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gelinsky
authors.affiliation: Center for Orthopaedics and Traumatology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.|Center for Translational Bone, Joint, and Soft Tissue Research, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Günther
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, California.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.affiliation: Center for Orthopaedics and Traumatology, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.|Center for Translational Bone, Joint, and Soft Tissue Research, University Hospital Carl Gustav Carus at Technische Universität Dresden, Dresden, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Stiehler
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000737:chemistry / Q000494:pharmacology; D024042:Collagen Type I / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D005269:Femur / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D006493:Heparin / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; D024042:Collagen Type I; C515256:Cxcl12 protein, mouse; D003692:Delayed-Action Preparations; D006493:Heparin
keywords: BMP-2; CXCL12; SDF-1α; critical size bone defect; heparinized mineralized collagen type I matrix scaffolds; segmental bone defect