title: Regeneration of bone using nanoplex delivery of FGF-2 and BMP-2 genes in diaphyseal long bone radial defects in a diabetic rabbit model.
abstract: Bone fracture healing impairment related to systemic diseases such as diabetes can be addressed by growth factor augmentation. We previously reported that growth factors such as fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) work synergistically to encourage osteogenesis in vitro. In this report, we investigated if BMP-2 and FGF-2 together can synergistically promote bone repair in a leporine model of diabetes mellitus, a condition that is known to be detrimental to union. We utilized two kinds of plasmid DNA encoding either BMP-2 or FGF-2 formulated into polyethylenimine (PEI) complexes. The fabricated nanoplexes were assessed for their size, charge, in vitro cytotoxicity, and capacity to transfect human bone marrow stromal cells (BMSCs). Using diaphyseal long bone radial defects in a diabetic rabbit model it was demonstrated that co-delivery of PEI-(pBMP-2+pFGF-2) embedded in collagen scaffolds resulted in a significant improvement in bone regeneration compared to PEI-pBMP-2 embedded in collagen scaffolds alone. This study demonstrated that scaffolds loaded with PEI-(pBMP-2+pFGF-2) could be an effective way of promoting bone regeneration in patients with diabetes.
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA, United States.
authors.forename: Behnoush
authors.initials: B
authors.lastname: Khorsand
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA, United States.
authors.forename: Nate
authors.initials: N
authors.lastname: Nicholson
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA, United States.
authors.forename: Anh-Vu
authors.initials: AV
authors.lastname: Do
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Femino
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Martin
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Petersen
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Guetschow
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA, United States.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Fredericks
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa College of Pharmacy, Iowa City, IA, United States. Electronic address: aliasger-salem@uiowa.edu.
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D001861:Bone Regeneration; D002460:Cell Line; D003094:Collagen / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D048909:Diabetes Complications / Q000235:genetics / Q000628:therapy*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010012:Osteogenesis; D011094:Polyethyleneimine / Q000737:chemistry; D011817:Rabbits; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D055396:Bone Morphogenetic Protein 2; D016222:Fibroblast Growth Factor 2; D011094:Polyethyleneimine; D003094:Collagen; D004247:DNA
keywords: Bone morphogenetic protein-2 (BMP-2); Bone regeneration; Diabetes mellitus; Fibroblast growth factor-2 (FGF-2); Non-viral gene delivery; Polyethylenimine