title: Synthetic thermoreversible polymers are compatible with osteoinductive activity of recombinant human bone morphogenetic protein 2.
abstract: Recombinant human bone morphogenetic protein 2 (rhBMP-2) is currently in clinical studies as part of an implantable device that contains a biomaterial carrier. Implant retention of rhBMP-2 by the biomaterial carrier is important for the osteoinductive activity. To control in situ retention of rhBMP-2, thermoreversible polymers were synthesized and characterized, and their compatibility with rhBMP-2-induced osteoinduction was investigated. The results indicated that polymers with a controlled "solubility <--> insolubility" transition temperature could be prepared from N-isopropylacrylamide, ethylmethacrylate, and N-acryloxysuccinimide (NASI). NASI-containing polymers were able to conjugate to rhBMP-2 without additional cross-linkers. Implantation in the rat ectopic model, where alkaline phosphatase and calcium deposition were utilized as markers of osteoinductive activity, indicated that rhBMP-2 mixed with the polymers were effective for osteoinduction. Moreover, rhBMP-2 conjugated to the chosen polymers was as effective as native rhBMP-2 in inducing ALP activity and calcium deposition. We conclude that thermoreversible polymers are compatible with rhBMP-2-induced osteogenesis and can serve as novel biomaterials for rhBMP-2 delivery.
authors.affiliation: Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta T6G 2G6, Canada.
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Gao
authors.forename: Niki A
authors.initials: NA
authors.lastname: Kousinioris
authors.forename: John M
authors.initials: JM
authors.lastname: Wozney
authors.forename: Shelley
authors.initials: S
authors.lastname: Winn
authors.forename: Hasan
authors.initials: H
authors.lastname: Uludag
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004343:Drug Implants; D006801:Humans; D008422:Materials Testing; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D011108:Polymers / Q000737:chemistry; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012995:Solubility; D013696:Temperature; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004343:Drug Implants; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000469:Alkaline Phosphatase; D002118:Calcium