Regular Article

Cell and Tissue Research

, Volume 347, Issue 3, pp 575-588

First online:

Synthetic scaffold coating with adeno-associated virus encoding BMP2 to promote endogenous bone repair

  • Kenneth M. DupontAffiliated withParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of TechnologyGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of TechnologyExponent Failure Analysis Associates
  • , Joel D. BoerckelAffiliated withParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of TechnologyGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology
  • , Hazel Y. StevensAffiliated withParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of TechnologyGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology
  • , Tamim DiabAffiliated withParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of TechnologyGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology
  • , Yash M. KolambkarAffiliated withParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of TechnologyWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology
  • , Masahiko TakahataAffiliated withCenter for Musculoskeletal Research, School of Medicine and Dentistry, University of Rochester
  • , Edward M. SchwarzAffiliated withCenter for Musculoskeletal Research, School of Medicine and Dentistry, University of Rochester
  • , Robert E. GuldbergAffiliated withParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of TechnologyGeorge W. Woodruff School of Mechanical Engineering, Georgia Institute of TechnologyWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Biomaterial scaffolds functionalized to stimulate endogenous repair mechanisms via the incorporation of osteogenic cues offer a potential alternative to bone grafting for the treatment of large bone defects. We first quantified the ability of a self-complementary adeno-associated viral vector encoding bone morphogenetic protein 2 (scAAV2.5-BMP2) to enhance human stem cell osteogenic differentiation in vitro. In two-dimensional culture, scAAV2.5-BMP2-transduced human mesenchymal stem cells (hMSCs) displayed significant increases in BMP2 production and alkaline phosphatase activity compared with controls. hMSCs and human amniotic-fluid-derived stem cells (hAFS cells) seeded on scAAV2.5-BMP2-coated three-dimensional porous polymer Poly(ε-caprolactone) (PCL) scaffolds also displayed significant increases in BMP2 production compared with controls during 12 weeks of culture, although only hMSC-seeded scaffolds displayed significantly increased mineral formation. PCL scaffolds coated with scAAV2.5-BMP2 were implanted into critically sized immunocompromised rat femoral defects, both with or without pre-seeding of hMSCs, representing ex vivo and in vivo gene therapy treatments, respectively. After 12 weeks, defects treated with acellular scAAV2.5-BMP2-coated scaffolds displayed increased bony bridging and had significantly higher bone ingrowth and mechanical properties compared with controls, whereas defects treated with scAAV2.5-BMP2 scaffolds pre-seeded with hMSCs failed to display significant differences relative to controls. When pooled, defect treatment with scAAV2.5-BMP2-coated scaffolds, both with or without inclusion of pre-seeded hMSCs, led to significant increases in defect mineral formation at all time points and increased mechanical properties compared with controls. This study thus presents a novel acellular bone-graft-free endogenous repair therapy for orthotopic tissue-engineered bone regeneration.

Keywords

Synthetic scaffold Large bone defect Self-complementary adeno-associated virus (scAAV) Bone morphogenetic protein-2 (BMP2) Stem cells Human