Electrospun Nanofiber Meshes for the Repair of Bone Defects
Joel D. Boerckel, Georgia Institute of Technology
Fracture nonunion is a frequent clinical problem, with more than 500,000 grafting
procedures performed annually in the U.S. alone. In an attempt to solve this problem, tissue engineering research has focused on therapeutic strategies involving the delivery of biological agents along with biodegradable scaffolds. Electrospun nanofiber meshes are a unique type of scaffold that possesses structural features that scale-wise resemble the extracellular matrix.
They may be useful as a membrane to guide bone regeneration by host cells or as a delivery vehicle for exogenous cells in vivo. In order to identify conditions that best support osteoprogenitor cells bridging the defect, the mesh structure and composition can be modified to enhance cellular migration and osteogenic differentiation.
Recently it has been demonstrated that the triple-helical collagen mimetic peptide, glycine-phenylalanine-hydroxyproline-glycine-glutamate-arginine (GFOGER), enhances adhesion and osteogenic differentiation of progenitor cells by its interaction with the α2β1 integrin.
In addition, studies have shown that nanofiber alignment affects cellular morphology, proliferation and migration, as well as matrix deposition.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) and rhBMP-7 have been
approved for the treatment of certain fractures, oral-maxillofacial applications and spinal fusion.
Currently, these osteoinductive proteins are delivered in solution on a purified type I collagen matrix. Due to this bolus delivery of BMPs, high doses (3.5 – 12 mg) are required for obtaining a substantial healing response. The high doses have resulted in an increased cost and complications arising due to diffusion of the BMP away from the defect site. Numerous sustained delivery vehicles are being developed to improve protein pharmacokinetics in vivo. Spatial regulation of the protein is also important to maximize efficacy and minimize side effects.