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Impact of IGF-I release kinetics on bone healing: A preliminary study in sheep

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dc.contributor.author Luginbuehl, V en
dc.contributor.author Zoidis, E en
dc.contributor.author Meinel, L en
dc.contributor.author Von Rechenberg, B en
dc.contributor.author Gander, B en
dc.contributor.author Merkle, HP en
dc.date.accessioned 2014-06-06T06:52:37Z
dc.date.available 2014-06-06T06:52:37Z
dc.date.issued 2013 en
dc.identifier.issn 09396411 en
dc.identifier.uri http://dx.doi.org/10.1016/j.ejpb.2013.03.004 en
dc.identifier.uri http://62.217.125.90/xmlui/handle/123456789/6088
dc.subject Bone healing en
dc.subject Gene expression en
dc.subject Insulin-like growth factor I (IGF-I) en
dc.subject Osteoinduction en
dc.subject PLGA microspheres en
dc.subject Release kinetics en
dc.subject.other recombinant somatomedin B en
dc.subject.other animal cell en
dc.subject.other article en
dc.subject.other bone defect en
dc.subject.other down regulation en
dc.subject.other encapsulation en
dc.subject.other fracture healing en
dc.subject.other human en
dc.subject.other human cell en
dc.subject.other in vitro study en
dc.subject.other kinetics en
dc.subject.other marker gene en
dc.subject.other mouse en
dc.subject.other nonhuman en
dc.subject.other ossification en
dc.subject.other Bone healing en
dc.subject.other Gene expression en
dc.subject.other Insulin-like growth factor I (IGF-I) en
dc.subject.other Osteoinduction en
dc.subject.other PLGA microspheres en
dc.subject.other Release kinetics en
dc.subject.other Animals en
dc.subject.other Bone and Bones en
dc.subject.other Bone Regeneration en
dc.subject.other Cell Line, Tumor en
dc.subject.other Drug Compounding en
dc.subject.other Drug Delivery Systems en
dc.subject.other Drug Implants en
dc.subject.other Gene Expression Regulation en
dc.subject.other Growth Substances en
dc.subject.other Humans en
dc.subject.other Inflammation Mediators en
dc.subject.other Insulin-Like Growth Factor I en
dc.subject.other Kinetics en
dc.subject.other Lactic Acid en
dc.subject.other Microspheres en
dc.subject.other Osteogenesis en
dc.subject.other Polyesters en
dc.subject.other Polyglycolic Acid en
dc.subject.other Random Allocation en
dc.subject.other Recombinant Proteins en
dc.subject.other Sheep, Domestic en
dc.subject.other Solubility en
dc.subject.other Wound Healing en
dc.title Impact of IGF-I release kinetics on bone healing: A preliminary study in sheep en
heal.type journalArticle en
heal.identifier.primary 10.1016/j.ejpb.2013.03.004 en
heal.publicationDate 2013 en
heal.abstract Spatiotemporal release of growth factors from a delivery device can profoundly affect the efficacy of bone growth induction. Here, we report on a delivery platform based on the encapsulation of insulin-like growth factor I (IGF-I) in different poly(d,l-lactide) (PLA) and poly(d,l-lactide-co-glycolide) (PLGA) microsphere (MS) formulations to control IGF-I release kinetics. In vitro IGF-I release profiles generally exhibited an initial burst (14-36% of total IGF-I content), which was followed by a more or less pronounced dormant phase with little release (2 to 34 days), and finally, a third phase of re-increased IGF-I release. The osteoinductive potential of these different IGF-I PL(G)A MS formulations was tested in studies using 8-mm metaphyseal drill hole bone defects in sheep. Histomorphometric analysis at 3 and 6 weeks after surgery showed that new bone formation was improved in the defects locally treated with IGF-I PL(G)A MS (n = 5) as compared to defects filled with IGF-I-free PL(G)A MS (n = 4). The extent of new bone formation was affected by the particular release kinetics, although a definitive relationship was not evident. Local administration of IGF-I resulted in down-regulation of inflammatory marker genes in all IGF-I treated defects. The over-expression of growth factor genes in response to IGF-I delivery was restricted to formulations that produced osteogenic responses. These experiments demonstrate the osteoinductive potential of sustained IGF-I delivery and show the importance of delivery kinetics for successful IGF-I-based therapies. © 2013 Elsevier B.V. All rights reserved. en
heal.journalName European Journal of Pharmaceutics and Biopharmaceutics en
dc.identifier.issue 1 en
dc.identifier.volume 85 en
dc.identifier.doi 10.1016/j.ejpb.2013.03.004 en
dc.identifier.spage 99 en
dc.identifier.epage 106 en


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