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J Biomed Mater Res A. 2016 Aug;104(8):2099-107. doi: 10.1002/jbm.a.35735. Epub 2016 Jun 3.

Scaffold-mediated BMP-2 minicircle DNA delivery accelerated bone repair in a mouse critical-size calvarial defect model.

Author information

1
Department of Orthopaedic Surgery, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.
2
Department of Bioengineering, Stanford University School of Medicine, Clark Center E-150, 300 Pasteur Drive, Edwards R105, MC5341, Stanford, California, 94305.
3
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.
4
Department of Chemistry, Stanford University, 333 Campus Drive Mudd Building, Room 121 Stanford, Stanford, California, 94305-4401.

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.

KEYWORDS:

BMP2; bone regeneration; minicircle; scaffold

PMID:
27059085
PMCID:
PMC5127622
DOI:
10.1002/jbm.a.35735
[Indexed for MEDLINE]
Free PMC Article

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