Pre-incubation of chemically crosslinked hyaluronan-based hydrogels, loaded with BMP-2 and hydroxyapatite, and its effect on ectopic bone formation.
The effects of pre-incubation of hyaluronan hydrogels, for different lengths of time after the initiation of chemical crosslinking and prior to injection, were explored both by investigating the in vitro BMP-2 release kinetics from the hydrogel and by studying the ectopic bone formation in rats. From the curing profile, obtained from rheological analysis, appropriate pre-incubation times (1 min, 5 h and 3 days) were selected, to prepare slightly, moderately and fully cured hydrogels. Comparable release profiles were observed for all three test groups in vitro. Furthermore, radiography, pQCT and histology of the explanted grafts showed cancellous bone formation in all groups after 5 weeks in vivo. However, longer pre-incubation times gave rise to an increase in bone volume, but a decrease in bone density. Moreover, the 5 h and the 3 days grafts appeared to be more ordered and resistant to deformation from the surrounding tissue than the 1 min grafts. The observed variations in mechanical and biological properties could potentially be used to adapt the treatment for a specific indication.
Department of Chemistry - Ångström Laboratory, Uppsala University, Box 538, 751 21, Uppsala, Sweden.
Sonya
S
Stenfelt
Gry
G
Hulsart-Billström
Lars
L
Gedda
Kristoffer
K
Bergman
Jöns
J
Hilborn
Sune
S
Larsson
Tim
T
Bowden
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D018786:Bone Substitutes / Q000737:chemistry; D003432:Cross-Linking Reagents; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D012212:Rheology
C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D020100:Hydrogels; D011994:Recombinant Proteins; D006820:Hyaluronic Acid; D017886:Durapatite