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Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep.
Journal article

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

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  • 2013-08-21
Published in:
  • European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. - 2013
Bone healing
Gene expression
Insulin-like growth factor I (IGF-I)
Osteoinduction
PLGA microspheres
Release kinetics
Animals
Bone Regeneration
Bone and Bones
Cell Line, Tumor
Drug Compounding
Drug Delivery Systems
Drug Implants
Gene Expression Regulation
Growth Substances
Humans
Inflammation Mediators
Insulin-Like Growth Factor I
Kinetics
Lactic Acid
Microspheres
Osteogenesis
Polyesters
Polyglycolic Acid
Polylactic Acid-Polyglycolic Acid Copolymer
Random Allocation
Recombinant Proteins
Sheep, Domestic
Solubility
Wound Healing
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/217274
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