title: Retention of transforming growth factor beta1 using functionalized dextran-based hydrogels.
abstract: Functionalized dextrans (FD) are anionic water-soluble polymers bearing carboxylate, benzylamide and sulfate groups, which exhibit binding capacity to transforming growth factor-beta1 (TGF-beta1). In this paper, we have investigated the ability of dextran-based hydrogels containing FD, to bind and release recombinant human TGF-beta1. Hydrogels were prepared by chemical crosslink native dextran and FD with sodium trimetaphosphate in 1m NaOH at 50 degrees C. A wide range of hydrogels were prepared as particles ranging of 1-1.6mm of diameter and characterized with various amounts of FD and with different crosslinker feeding ratios (CFR). Dried particles were soaked with recombinant human transforming growth factor-beta1 (rhTGF-beta1) to determine their capacity to deliver the growth factor. Results indicated that the in vitro kinetics releases of rhTGF-beta1 were related to FD and CFR. Retention capacity of rhTGF-beta1 increases with an increase of negative charges of the matrices brought by both phosphate linkages and FD as demonstrated by an additional release of growth factor in high ionic strength solution. Highly crosslinked hydrogels that contained the highest amount of FD (18% (w/w)) retained up to 88% of rhTGF-beta1. Bioactivity of released growth factor was confirmed in a cell assay. These functionalized hydrogels may have important uses for the stabilization and the protection of rhTGF-beta1 as entrapment systems and could be applied to other proteins of clinical interest.
authors.affiliation: Laboratoire de Bio-ingénierie de Polymères Cardiovasculaires, ERIT-M Inserm 0204, X. Bichat Hospital, Paris, Université Paris 13 and Université Paris 7, 75877 Paris Cedex 18, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Maire
authors.forename: Delphine
authors.initials: D
authors.lastname: Logeart-Avramoglou
authors.forename: Marie-Christelle
authors.initials: MC
authors.lastname: Degat
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chaubet
mesh_terms: D000042:Absorption; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry*; D004058:Diffusion; D004343:Drug Implants / Q000008:administration & dosage* / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D020100:Hydrogels / Q000737:chemistry*; D008168:Lung; D008422:Materials Testing; D051379:Mice; D013499:Surface Properties; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry*; D053773:Transforming Growth Factor beta1
chemical_list: D001672:Biocompatible Materials; D003911:Dextrans; D004343:Drug Implants; D020100:Hydrogels; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1