title: Effect of calcium phosphate coating and rhBMP-2 on bone regeneration in rabbit calvaria using poly(propylene fumarate) scaffolds.
abstract: Various calcium phosphate based coatings have been evaluated for better bony integration of metallic implants and are currently being investigated to improve the surface bioactivity of polymeric scaffolds. The aim of this study was to evaluate the role of calcium phosphate coating and simultaneous delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the in vivo bone regeneration capacity of biodegradable, porous poly(propylene fumarate) (PPF) scaffolds. PPF scaffolds were coated with three different calcium phosphate formulations: magnesium-substituted β-tricalcium phosphate (β-TCMP), carbonated hydroxyapatite (synthetic bone mineral, SBM) and biphasic calcium phosphate (BCP). In vivo bone regeneration was evaluated by implantation of scaffolds in a critical-sized rabbit calvarial defect loaded with different doses of rhBMP-2. Our data demonstrated that scaffolds with each of the calcium phosphate coatings were capable of sustaining rhBMP-2 release and retained an open porous structure. After 6weeks of implantation, micro-computed tomography revealed that the rhBMP-2 dose had a significant effect on bone formation within the scaffolds and that the SBM-coated scaffolds regenerated significantly greater bone than BCP-coated scaffolds. Mechanical testing of the defects also indicated restoration of strength in the SBM and β-TCMP with rhBMP-2 delivery. Histology results demonstrated bone growth immediately adjacent to the scaffold surface, indicating good osteointegration and osteoconductivity for coated scaffolds. The results obtained in this study suggest that the coated scaffold platform demonstrated a synergistic effect between calcium phosphate coatings and rhBMP-2 delivery and may provide a promising platform for the functional restoration of large bone defects.
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: Mahrokh
authors.initials: M
authors.lastname: Dadsetan
authors.affiliation: Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: Teja
authors.initials: T
authors.lastname: Guda
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: M Brett
authors.initials: MB
authors.lastname: Runge
authors.affiliation: Department of Biomaterials & Biomimetics, New York University, New York, NY, USA.
authors.forename: Dindo
authors.initials: D
authors.lastname: Mijares
authors.affiliation: Department of Biomaterials & Biomimetics, New York University, New York, NY, USA.
authors.forename: Racquel Z
authors.initials: RZ
authors.lastname: LeGeros
authors.affiliation: Department of Biomaterials & Biomimetics, New York University, New York, NY, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: LeGeros
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Silliman
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: Lichun
authors.initials: L
authors.lastname: Lu
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wenke
authors.affiliation: United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA.
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Brown Baer
authors.affiliation: Biomaterials and Tissue Engineering Laboratory, Mayo Clinic, Rochester, MN, USA. Electronic address: yaszemski.michael@mayo.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates / Q000494:pharmacology*; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D005260:Female; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007700:Kinetics; D011126:Polypropylenes / Q000494:pharmacology*; D016062:Porosity; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects*; D013052:Spectrometry, X-Ray Emission; D054457:Tissue Scaffolds / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D005650:Fumarates; D011126:Polypropylenes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C097850:poly(propylene fumarate); C499469:recombinant human bone morphogenetic protein-2; C020243:calcium phosphate
keywords: 3-D printing; Bone regeneration; Calcium phosphate coating; Poly(propylene fumarate); Rabbit calvarial defect