Regeneration of bone using nanoplex delivery of FGF-2 and BMP-2 genes in diaphyseal long bone radial defects in a diabetic rabbit model
Autor: | Aliasger K. Salem, John E. Femino, Brian Guetschow, Behnoush Khorsand, Emily B Petersen, Douglas C. Fredericks, Anh-Vu Do, Nate Nicholson, James A. Martin |
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Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Bone Regeneration Stromal cell medicine.medical_treatment Long bone Bone Morphogenetic Protein 2 Pharmaceutical Science 02 engineering and technology Bone healing Bone morphogenetic protein 2 Article Cell Line Diabetes Complications 03 medical and health sciences Osteogenesis medicine Animals Humans Polyethyleneimine Bone regeneration Tissue Scaffolds Chemistry Regeneration (biology) Growth factor Gene Transfer Techniques DNA Genetic Therapy 021001 nanoscience & nanotechnology Nanostructures Surgery Bone morphogenetic protein 7 030104 developmental biology medicine.anatomical_structure Cancer research Fibroblast Growth Factor 2 Collagen Rabbits 0210 nano-technology |
Zdroj: | Journal of Controlled Release. 248:53-59 |
ISSN: | 0168-3659 |
Popis: | 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. |
Databáze: | OpenAIRE |
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