title: The evaluation of ectopic bone formation induced by delivery systems for bone morphogenetic protein-9 or its derived peptide.
abstract: We have earlier shown that a peptide derived from the bone morphogenetic protein-9 (pBMP-9) stimulates mouse preosteoblasts MC3T3-E1 differentiation in vitro. Here, we evaluated the effects of two delivery systems (DSs) for pBMP-9, one based on collagen and the other on chitosan. The release kinetics of BMP-9 (used as control) and pBMP-9 from these DSs were first determined in vitro by using enzyme-linked immunosorbent assay and high performance liquid chromatography assays, respectively. Micro-computerized tomography and histological analysis were then performed to study in vivo the ectopic ossification induced by both DSs containing these molecules in C57BL/6 mouse quadriceps. We found that collagen DS released in vitro about 35% of its BMP-9 within 1 h, whereas chitosan DS released 80%. The pBMP-9 was released from both DSs more slowly for up to 10 days. These release kinetics seemed to fit the Korsmeyer-Peppas model. Only chitosan DS containing BMP-9 induced strong bone formation in all mice quadriceps within 24 days. All mice quadriceps treated by pBMP-9 trapped in this DS also favored bone structures that started to mineralize. However, pBMP-9 in collagen DS failed to promote ectopic ossification within 24 days in vivo. This study highlights the importance to optimize carrier, thus improving the efficiency of pBMP-9 in vivo.
authors: Laboratory of Cell-Biomaterial Biohybrid Systems, Department of Chemical Engineering and Biotechnological Engineering, Faculty of Engineering, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors: Eric
authors: E
authors: Bergeron
authors: Elisabeth
authors: E
authors: Leblanc
authors: Olivier
authors: O
authors: Drevelle
authors: Randy
authors: R
authors: Giguère
authors: Sabrina
authors: S
authors: Beauvais
authors: Guillaume
authors: G
authors: Grenier
authors: Nathalie
authors: N
authors: Faucheux
mesh_terms: D000818:Animals; D016466:CHO Cells; D002828:Choristoma / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D016503:Drug Delivery Systems / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D055427:Growth Differentiation Factor 2 / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D055427:Growth Differentiation Factor 2; D010455:Peptides