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Injectable hydrogel carriers for the delivery of exo- and endogenous growth factors for bone regeneration

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Defense Thèse de doctorat : Univ. Genève, 2010 - Sc. 4233 - 2010/07/09
Abstract Bone regeneration may benefit from the local delivery of bone-promoting growth factors. In this view, we developed, optimized and evaluated in vivo a novel syringeable hydrogel based on chitosan, intended as a drug carrier. The effect of the carrier pH and nature on recombinant human Bone morphogenetic protein-2 (rhBMP-2) bioactivity was demonstrated. As for carrier pH, rhBMP-2 bone-forming ability decreased when shifting hydrogel pH from acidic to neutral conditions. Observed aggregation and conformational changes of rhBMP-2 in solution might explain the decrease of growth factor bioactivity. Although combining rhBMP-2 with a cross-linked hyaluronan hydrogel induced formation of higher amounts of bone, a more mature bone was observed with the chitosan hydrogel carrier. The addition of β-tricalcium phosphate to chitosan hydrogel increased rhBMP-2-induced bone formation. Finally, the sustained release of a platelet growth factor from chitosan hydrogel formulations demonstrated the potential of this approach as an alternative to exogenous growth factors.
Keywords Bone regenerationBone repairBMP-2AggregationPhysical stabilityFluorescence spectroscopyNile Red1,8-ANSLight scatteringElectron microscopyChitosan hydrogelHyaluronan hydrogelβ-tricalcium phosphate (β-TCP)Formulation pHBioactivityRat ectopic bone formationPlatelet-rich plasmaPDGF-BBControlled release
Stable URL https://archive-ouverte.unige.ch/unige:15035
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URN: urn:nbn:ch:unige-150353
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Deposited on : 2011-05-02

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