title: Enhanced osseous integration of human trabecular allografts following surface modification with bioactive lipids.
abstract: In this study, we used extracellular matrix (ECM) gels and human bone allograft as matrix vehicles to deliver the sphingolipid growth factor FTY720 to rodent models of tibial fracture and a critical-sized cranial defect. We show that FTY720 released from injectable ECM gels may accelerate callous formation and resolution and bone volume in a mouse tibial fracture model. We then show that FTY720 binds directly to human trabecular allograft bone and releases over 1 week in vitro. Rat critical-sized cranial defects treated with FTY720-coated grafts show increases in vascularization and bone deposition, with histological and micro-computed topography (microCT) evidence of enhanced bone formation within the graft and defect void. Immunohistochemical analysis suggests that osteogenesis within FTY720-coated grafts is associated with reduced CD68(+) macrophage infiltration and recruitment of CD29(+) bone progenitor cells. Matrix binding of FTY720 thus represents a promising and robust bone regeneration strategy with potential clinical translatability.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive Rm 1311, Atlanta, GA, 30332, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Wang
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive Rm 1311, Atlanta, GA, 30332, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Krieger
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22903, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22903, USA.
authors.forename: Anusuya
authors.initials: A
authors.lastname: Das
authors.affiliation: LifeNet Health, Virginia Beach, VA, 23453, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Francis
authors.affiliation: School of Medical Diagnostic and Translational Science, Old Dominion University, Norfolk, VA, 23529, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Ogle
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive Rm 1311, Atlanta, GA, 30332, USA. edward.botchwey@bme.gatech.edu.
authors.forename: Edward
authors.initials: E
authors.lastname: Botchwey
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D016025:Bone Transplantation / Q000379:methods; D000071556:Cancellous Bone / Q000166:cytology* / Q000187:drug effects; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000737:chemistry*; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage* / Q000494:pharmacology; D050723:Fractures, Bone / Q000628:therapy*; D006801:Humans; D051379:Mice; D051381:Rats; D012886:Skull / Q000293:injuries*; D013977:Tibia / Q000293:injuries*; D014184:Transplantation, Homologous
chemical_list: D000068876:Fingolimod Hydrochloride
keywords: Bone allograft; Extracellular matrix; FTY720; Regeneration; Sphingosine 1-phosphate