The enhancement of bone allograft incorporation by the local delivery of the sphingosine 1-phosphate receptor targeted drug FTY720.

Biomaterials
Caren E Petrie AroninEdward A Botchwey

Abstract

Poor vascularization coupled with mechanical instability is the leading cause of post-operative complications and poor functional prognosis of massive bone allografts. To address this limitation, we designed a novel continuous polymer coating system to provide sustained localized delivery of pharmacological agent, FTY720, a selective agonist for sphingosine 1-phosphate receptors, within massive tibial defects. In vitro drug release studies validated 64% loading efficiency with complete release of compound following 14 days. Mechanical evaluation following six weeks of healing suggested significant enhancement of mechanical stability in FTY720 treatment groups compared with unloaded controls. Furthermore, superior osseous integration across the host-graft interface, significant enhancement in smooth muscle cell investment, and reduction in leukocyte recruitment was evident in FTY720 treated groups compared with untreated groups. Using this approach, we can capitalize on the existing mechanical and biomaterial properties of devitalized bone, add a controllable delivery system while maintaining overall porous structure, and deliver a small molecule compound to constitutively target vascular remodeling, osseous remodeling, and mini...Continue Reading

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Citations

Aug 25, 2011·Cell and Tissue Research·Cynthia HuangEdward Botchwey
Sep 10, 2011·Tissue Engineering. Part B, Reviews·Anusuya Das, Edward Botchwey
Dec 3, 2015·Drug Delivery and Translational Research·Ok Hee Jeon, Jennifer Elisseeff
Jun 17, 2015·Advanced Drug Delivery Reviews·Yang-Hee Kim, Yasuhiko Tabata
May 12, 2015·Advanced Drug Delivery Reviews·Elizabeth R Balmayor
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Oct 22, 2014·Annals of Biomedical Engineering·Kara L SpillerGordana Vunjak-Novakovic
Dec 18, 2018·Advanced Healthcare Materials·Kristopher A White, Ronke M Olabisi
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Dec 4, 2016·Tissue Engineering. Part B, Reviews·Johnathan NgGordana Vunjak-Novakovic
Jul 27, 2018·Frontiers of Medicine·Rui ShiWei Tian
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Aug 21, 2021·Chemical Reviews·Ricardo WhitakerKara L Spiller

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