title: Effect of initial pBMP-9 loading and collagen concentration on the kinetics of peptide release and a mathematical model of the delivery system.
abstract: Type I collagen is one of the most widely used materials for drug delivery in tissue repair. It is the reference carrier for delivering growth factors like bone morphogenetic proteins (BMPs such as BMP-2 and BMP-7) for bone repair. Since BMPs are expensive to produce, we have developed a peptide derived from BMP-9 (pBMP-9) that is 300 times less expensive than the entire protein while still promoting osteogenic differentiation. We have now evaluated the effects of the collagen concentration and the initial pBMP-9 load on peptide release. We then developed a model of pBMP-9 release kinetics by finite differences using a system based on Fick's second law in which the interactions between the peptide and collagen fibers are assumed to follow Langmuir adsorption kinetics. The Langmuir isotherms suggest that the structure of the collagen gel influences the strength of its electrostatic interaction with the peptide, since increasing the collagen concentration decreased the affinity of pBMP-9 for the collagen. The resulting model of the mechanism accurately reflects the experimental data and the parameters estimated indicate that the diffusivities with the different collagen concentrations are similar, whereas the mass transfer coefficient increases with the collagen concentration. The results also indicate that perfect sink conditions cannot be assumed and suggest the presence of an optimal collagen concentration. Finally, we have correlated our conclusions with the differences in collagen fiber organization observed by transmission electron microscopy.
authors.affiliation: Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, 2500 boul. de l'Université, Sherbrooke, Québec J1K 2R1, Canada; Canada Research Chair in Cell-Biomaterial Biohybrid Systems Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, 2500 boul. de l'Université, Sherbrooke, Québec J1K 2R1, Canada.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Lauzon
authors.affiliation: Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, 2500 boul. de l'Université, Sherbrooke, Québec J1K 2R1, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Marcos
authors.affiliation: Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, 2500 boul. de l'Université, Sherbrooke, Québec J1K 2R1, Canada; Canada Research Chair in Cell-Biomaterial Biohybrid Systems Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, 2500 boul. de l'Université, Sherbrooke, Québec J1K 2R1, Canada. Electronic address: nathalie.faucheux@usherbrooke.ca.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faucheux
mesh_terms: D024042:Collagen Type I / Q000737:chemistry*; D016503:Drug Delivery Systems; D055427:Growth Differentiation Factor 2 / Q000737:chemistry*; D020100:Hydrogels; D007700:Kinetics; D008962:Models, Theoretical; D010455:Peptides / Q000737:chemistry*
chemical_list: D024042:Collagen Type I; D055427:Growth Differentiation Factor 2; D020100:Hydrogels; D010455:Peptides
keywords: Bone regeneration; Electrostatic interactions; Mass transport; Peptides