title: Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation.
abstract: Bone morphogenetic protein-2 (BMP-2) is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed BMP-2 with the glycosaminoglycans (GAGs) dermatan sulfate (DS) or heparin (HP), prior to loading it into a hyaluronic acid (HA) hydrogel. In vitro release studies showed that BMP-2 precomplexed with DS or HP had a prolonged delivery compared to without GAG. BMP-2-DS complexes achieved a slightly faster release in the first 24 h than HP; however, both delivered BMP-2 for an equal duration. Analysis of the kinetic interaction between BMP-2 and DS or HP showed that HP had approximately 10 times higher affinity for BMP-2 than DS, yet it equally stabilized the protein, as determined by alkaline phosphatase activity. Ectopic bone formation assays at subcutaneous sites in rats demonstrated that HA hydrogel-delivered BMP-2 precomplexed with GAG induced twice the volume of bone compared with BMP-2 delivered uncomplexed to GAG.
authors.affiliation: Division of Polymers Chemistry, Department of Chemistry-ångström, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Marta
authors.initials: M
authors.lastname: Kisiel
authors.forename: Agnieszka S
authors.initials: AS
authors.lastname: Klar
authors.forename: Manuela
authors.initials: M
authors.lastname: Ventura
authors.forename: Jos
authors.initials: J
authors.lastname: Buijs
authors.forename: Marc-Krystelle
authors.initials: MK
authors.lastname: Mafina
authors.forename: Simon M
authors.initials: SM
authors.lastname: Cool
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D055767:Immobilized Proteins / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D055767:Immobilized Proteins; D006820:Hyaluronic Acid