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Scaffold‐mediated BMP‐2 minicircle DNA delivery accelerated bone repair in a mouse critical‐size calvarial defect model
Author(s) -
Keeney Michael,
Chung Michael T.,
Zielins Elizabeth R.,
Paik Kevin J.,
McArdle Adrian,
Morrison Shane D.,
Ransom Ryan C.,
Barbhaiya Namrata,
Atashroo David,
Jacobson Gunilla,
Zare Richard N.,
Longaker Michael T.,
Wan Derrick C.,
Yang Fan
Publication year - 2016
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.35735
Subject(s) - minicircle , bone healing , scaffold , plga , materials science , gene delivery , bone morphogenetic protein 2 , microbiology and biotechnology , osteocalcin , biomedical engineering , transfection , regeneration (biology) , in vitro , biology , anatomy , dna , gene , nanotechnology , medicine , alkaline phosphatase , biochemistry , nanoparticle , enzyme
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 CO 2 , 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.