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

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• 作者：Michael Keeney ; Michael T. Chung ; Elizabeth R. Zielins ; Kevin J. Paik ; Adrian McArdle ; Shane D. Morrison ; Ryan C. Ransom ; Namrata Barbhaiya ; David Atashroo ; Gunilla Jacobson ; Richard N. Zare ; Michael T. Longaker ; Derrick C. Wan and Fan Yang
• 刊名：Journal of Biomedical Materials Research Part A
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：104
• 期：8
• 页码：2099-2107
• 全文大小：580K
• ISSN：1552-4965

文摘

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.