title: Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model.
abstract: Scaffold-mediated gene delivery holds great promise for tissue regeneration. However, previous attempts to induce bone regeneration using scaffold-mediated non-viral gene delivery rarely resulted in satisfactory healing. We report a novel platform with sustained release of minicircle DNA (MC) from PLGA scaffolds to accelerate bone repair. MC was encapsulated inside PLGA scaffolds using supercritical CO2 , which showed prolonged release of MC. Skull-derived osteoblasts transfected with BMP-2 MC in vitro result in higher osteocalcin gene expression and mineralized bone formation. When implanted in a critical-size mouse calvarial defect, scaffolds containing luciferase MC lead to robust in situ protein production up to at least 60 days. Scaffold-mediated BMP-2 MC delivery leads to substantially accelerated bone repair as early as two weeks, which continues to progress over 12 weeks. This platform represents an efficient, long-term nonviral gene delivery system, and may be applicable for enhancing repair of a broad range of tissues types. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2099-2107, 2016.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.|Department of Bioengineering, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.
authors.forename: Michael
authors.initials: M
authors.lastname: Keeney
authors.affiliation: Department of Surgery, Plastic and Reconstructive Surgery Division, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California, 94305-5148.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chung
authors.affiliation: Department of Surgery, Plastic and Reconstructive Surgery Division, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California, 94305-5148.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Zielins
authors.affiliation: Department of Surgery, Plastic and Reconstructive Surgery Division, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California, 94305-5148.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Paik
authors.affiliation: Department of Surgery, Plastic and Reconstructive Surgery Division, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California, 94305-5148.
authors.forename: Adrian
authors.initials: A
authors.lastname: McArdle
authors.affiliation: Department of Surgery, Plastic and Reconstructive Surgery Division, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California, 94305-5148.
authors.forename: Shane D
authors.initials: SD
authors.lastname: Morrison
authors.affiliation: Department of Surgery, Plastic and Reconstructive Surgery Division, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California, 94305-5148.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Ransom
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.|Department of Bioengineering, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.
authors.forename: Namrata
authors.initials: N
authors.lastname: Barbhaiya
authors.affiliation: Department of Surgery, Plastic and Reconstructive Surgery Division, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California, 94305-5148.
authors.forename: David
authors.initials: D
authors.lastname: Atashroo
authors.affiliation: Department of Chemistry, Stanford University, 333 Campus Drive Mudd Building, Room 121 Stanford, Stanford, California, 94305-4401.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Jacobson
authors.affiliation: Department of Chemistry, Stanford University, 333 Campus Drive Mudd Building, Room 121 Stanford, Stanford, California, 94305-4401.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Zare
authors.affiliation: Department of Surgery, Plastic and Reconstructive Surgery Division, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California, 94305-5148.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.affiliation: Department of Surgery, Plastic and Reconstructive Surgery Division, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, California, 94305-5148.
authors.forename: Derrick C
authors.initials: DC
authors.lastname: Wan
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.|Department of Bioengineering, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000378:metabolism; D004270:DNA, Circular / Q000378:metabolism*; D018014:Gene Transfer Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010012:Osteogenesis; D011100:Polyglycolic Acid / Q000737:chemistry; D012886:Skull / Q000473:pathology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D015854:Up-Regulation; D014945:Wound Healing; D055114:X-Ray Microtomography
chemical_list: D055396:Bone Morphogenetic Protein 2; D004270:DNA, Circular; D011100:Polyglycolic Acid; D008156:Luciferases
keywords: BMP2; bone regeneration; minicircle; scaffold