title: Biofunctionalizing devitalized bone allografts through polymer-mediated short and long term growth factor delivery.
abstract: According to 5- and 10-year clinical follow-up studies large-scale bone allografts have a high failure rate, largely due to poor allograft incorporation with adjacent bone and subsequent poor remodeling. The goal of this study was to develop a methodology to deliver growth factors from large-scale bone allografts in a temporally controlled manner. Intact long bone allografts were coated with a micron-scale thick layer of degradable polymer that maintained inherent pore structures and acted as a delivery vehicle for bone morphogenetic protein-2 and vascular endothelial growth factor. VEGF was loaded onto the surface of the polymer to produce rapid release, to encourage initial vascularization at the defect site, while BMP-2 was encapsulated within the polymer layer to promote a more sustained release, to encourage bone formation over time. Release kinetics from factor-loaded polymer-coated allografts show an early burst release of VEGF over the first 7 days followed by a more sustained release of BMP-2 over the second and third week. In vitro cell studies using human mesenchymal stem cells confirm the bioactivity of the released BMP-2. In-vivo results show robust bone formation over the first 8 weeks of healing in femoral segmental defects in rats implanted with BMP-2 loaded polymer-coated allografts. A microscale thin coating of degradable polymer on a large-scale bone allograft provides temporal control over the delivery of growth factor loaded onto one allograft, while maintaining its microscale pore structure. Enhancing the incorporation and subsequent remodeling of allografts would reduce the incidence of allograft failure over time, and potentially speed healing at the earliest stages after implantation.
authors.affiliation: Department of Materials Science and Engineering, University of Connecticut, Storrs, Connecticut.
authors.forename: Farzana
authors.initials: F
authors.lastname: Sharmin
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Douglas
authors.initials: D
authors.lastname: Adams
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Michael
authors.initials: M
authors.lastname: Pensak
authors.affiliation: Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dukas
authors.affiliation: Department of Orthopaedic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA.
authors.forename: Jay
authors.initials: J
authors.lastname: Lieberman
authors.affiliation: Department of Materials Science and Engineering, University of Connecticut, Storrs, Connecticut.|Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut.|Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Khan
mesh_terms: D064591:Allografts; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects; D018786:Bone Substitutes / Q000737:chemistry; D016025:Bone Transplantation / Q000379:methods*; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D020099:Coated Materials, Biocompatible; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A
keywords: adsorption; allografts; bone morphogenetic protein-2; critical defect; encapsulation; poly(lactide-co-glycolide); release kinetics; vascular endothelial growth factor