Regeneration of Bone Using Nanoplex Delivery of FGF-2 and BMP-2 Genes in Diaphyseal Long Bone Radial Defects in a Diabetic Rabbit Model

Overview

Journal J Control Release

Specialty Pharmacology

Date 2017 Jan 11

PMID 28069556

Citations 30

Authors

Behnoush Khorsand

Nate Nicholson

Anh-Vu Do

John E Femino

James A Martin

Emily Petersen

Brian Guetschow

Douglas C Fredericks

Aliasger K Salem

Affiliations

Soon will be listed here.

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.

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