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 |