title: Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment.
abstract: While human bone morphogenetic protein-2 (rhBMP-2) is a promising growth factor for bone regeneration, its clinical efficacy has recently shown to be below expectation. In order to improve the clinical translation of rhBMP-2, there exists strong motivation to engineer better delivery systems. Hyaluronic acid (HA) hydrogel is a suitable carrier for the delivery of rhBMP-2, but a major limitation of this scaffold is its low cell adhesive properties. In this study, we have determined whether covalent grafting of an integrin-specific ligands into HA hydrogel could improve cell attachment and further enhance the osteogenic potential of rhBMP-2. A structurally stabilized fibronectin (FN) fragment containing the major integrin-binding domain of full-length FN (FN III9*-10) was engineered, in order to be incorporated into HA hydrogel. Compared to non-functionalized HA hydrogel, HA-FN hydrogel remarkably improved the capacity of the material to support mesenchymal stem cell attachment and spreading. In an ectopic bone formation model in the rat, delivery of rhBMP-2 with HA-FN hydrogel resulted in the formation of twice as much bone with better organization of collagen fibers compared to delivering the growth factor in non-functionalized HA hydrogel. This engineered hydrogel carrier for rhBMP-2 can be relevant in clinical bone repair.
authors.affiliation: Division of Polymer Chemistry, Department of Chemistry-Ångström Laboratory, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Marta
authors.initials: M
authors.lastname: Kisiel
authors.forename: Mikaël M
authors.initials: MM
authors.lastname: Martino
authors.forename: Manuela
authors.initials: M
authors.lastname: Ventura
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Ossipov
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000494:pharmacology*; D001842:Bone and Bones / Q000098:blood supply / Q000187:drug effects / Q000648:ultrastructure; D002448:Cell Adhesion; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D055119:Elastic Modulus; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D005353:Fibronectins; D016023:Integrins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid