title: Analysis of hydrolyzable polyethylene glycol hydrogels and deproteinized bone mineral as delivery systems for glycosylated and non-glycosylated bone morphogenetic protein-2.
abstract: Bone morphogenetic proteins (BMP), in particular BMP-2, are the growth factors primarily responsible for osteoinduction. A knowledge of interactions between bone substitute materials and growth factor variants is crucial to designing bone substitutes with an ideal release profile. Here we compare glycosylated and non-glycosylated recombinant human bone morphogenetic protein-2 (rhBMP-2) either incorporated into a hydrolyzable polyethylene glycol (PEG) hydrogel developed as a slow release system or adsorbed to a deproteinized bovine bone matrix (DBBM), a clinically well-established bone substitute material. rhBMP-2 loaded materials were immersed in cell culture medium and rhBMP-2 concentration profiles in the supernatant were determined by an enzyme-linked immunosorbent assay. The corresponding biological activities were assessed in vitro by alkaline phosphatase activity assay. We show a strong affinity of rhBMP-2 for DBBM and reduced biological activity after its release from PEG hydrogels. Glycosylated rhBMP-2 was significantly less affected by the hydrogel and interacted significantly more strongly with DBBM than non-glycosylated rhBMP-2. We therefore question the combination of PEG hydrogels with DBBM as a rhBMP-2 delivery system over DBBM alone, since rhBMP-2 released from the hydrogel will be trapped by DBBM. Moreover, our results suggest that glycosylated rhBMP-2 is favorable in combination with PEG hydrogels, since its activity is better preserved, whereas in combination with DBBM non-glycosylated rhBMP-2 is favorable, benefiting from an initially higher concentration of free rhBMP-2.
authors.affiliation: Oral Biotechnology and Bioengineering, Department of Cranio-Maxillofacial Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hänseler
authors.forename: Ui-Won
authors.initials: UW
authors.lastname: Jung
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Jung
authors.forename: Kyoung-Hee
authors.initials: KH
authors.lastname: Choi
authors.forename: Kyoo-Sung
authors.initials: KS
authors.lastname: Cho
authors.forename: Christoph H F
authors.initials: CH
authors.lastname: Hämmerle
authors.forename: Franz E
authors.initials: FE
authors.lastname: Weber
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001842:Bone and Bones / Q000737:chemistry*; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D006031:Glycosylation; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D008422:Materials Testing; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D020100:Hydrogels; D011994:Recombinant Proteins; D011092:Polyethylene Glycols