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Enhanced osseous integration of human trabecular allografts following surface modification with bioactive lipids

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An Erratum to this article was published on 16 May 2016

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.

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Acknowledgments

This work was supported by NIH R01 DE019935 and NIH R01 AR056445.

Conflict of interest

T.W., J.K., C.H., A.D., R.O., and E.B. declare that they have no conflict of interest. M.P.F. is an employee of LifeNet Health.

Ethical standards and animal care

Experiments comply with the current laws of the USA. All institutional and national guidelines for the care and use of laboratory animals were followed.

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    Authors and Affiliations

    1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Drive Rm 1311, Atlanta, GA, 30332, USA

      Tiffany Wang, Jack Krieger & Edward Botchwey

    2. Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22903, USA

      Cynthia Huang & Anusuya Das

    3. LifeNet Health, Virginia Beach, VA, 23453, USA

      Michael P. Francis

    4. School of Medical Diagnostic and Translational Science, Old Dominion University, Norfolk, VA, 23529, USA

      Roy Ogle

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    1. Tiffany Wang
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    Correspondence to Edward Botchwey.

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    Tiffany Wang and Jack Krieger contributed equally to this work.

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    Wang, T., Krieger, J., Huang, C. et al. Enhanced osseous integration of human trabecular allografts following surface modification with bioactive lipids. Drug Deliv. and Transl. Res. 6, 96–104 (2016). https://doi.org/10.1007/s13346-015-0244-0

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