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

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 o...

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Published in:	Biomaterials Vol. 31; no. 25; pp. 6417 - 6424
Main Authors:	Petrie Aronin, Caren E, Shin, Soo J, Naden, Kimberly B, Rios, Peter D, Sefcik, Lauren S, Zawodny, Sarah R, Bagayoko, Namory D, Cui, Quanjun, Khan, Yusuf, Botchwey, Edward A
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-09-2010
Subjects:	Advanced Basic Science Angiogenesis Animals Bone and Bones - drug effects Bone and Bones - ultrastructure Bone Remodeling Bone tissue engineering Bone Transplantation - physiology Coated Materials, Biocompatible - chemistry Compressive Strength Dentistry Drug delivery Elastic Modulus Fingolimod Hydrochloride Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - therapeutic use Male Neovascularization, Physiologic Osseointegration Propylene Glycols - administration & dosage Propylene Glycols - therapeutic use Rats Rats, Sprague-Dawley Receptors, Lysosphingolipid - metabolism Sphingosine - administration & dosage Sphingosine - analogs & derivatives Sphingosine - therapeutic use Tissue Engineering Transplantation, Homologous Angiogenesis Osseointegration Bone tissue engineering Drug delivery
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Summary:	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 minimize fibrous encapsulation within the allograft–host bone interface. Such results support continued evaluation of drug-eluting allografts as a viable strategy to improve functional outcome and long-term success of massive cortical allograft implants.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0142-9612 1878-5905
DOI:	10.1016/j.biomaterials.2010.04.061