title: Injectable hydrogels embedded with alginate microspheres for controlled delivery of bone morphogenetic protein-2.
abstract: Some delivery carriers with injectable characteristics were built using the thermosensitive chitosan/dextran-polylactide/glycerophosphate hydrogel and selected alginate microspheres for the controllable release of bone morphogenetic protein-2 (BMP-2). BMP-2 was first loaded into the microspheres with an average size of around 20 μm and the resulting microspheres were then embedded into the gel in order to achieve well-controlled BMP-2 release. The microsphere-embedded gels show their incipient gelation temperature at around 32 °C and pH at about 7.1. Some gels had their elastic modulus close to 1400 Pa and the ratio of elastic modulus to viscous modulus at around 34, revealing that they behaved like mechanically strong gels. Optimized microsphere-embedded gels were found to be able to administer the BMP-2 release without significant initial burst release in an approximately linear manner over a period of time longer than four weeks. The release rate and the released amount of BMP-2 from these gels could be regulated individually or cooperatively by the initial BMP-2 load and the dextran-polylactide content in the gels. Measurements of the BMP-2 induced alkaline phosphatase activity in C2C12 cells confirmed that C2C12 cells responded to BMP-2 in a dose-dependent way and the released BMP-2 from the microsphere-embedded gels well retained their bioactivity. In vivo assessment of some gels revealed that the released BMP-2 maintained its osteogenesis functions.
authors.affiliation: Department of Stomatology, Zhongnan Hospital, Wuhan University, Wuhan 430071, People's Republic of China.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jiulong
authors.initials: J
authors.lastname: Wang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
mesh_terms: D000464:Alginates / Q000737:chemistry; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002460:Cell Line; D016503:Drug Delivery Systems; D055119:Elastic Modulus; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels; D008422:Materials Testing; D051379:Mice; D008863:Microspheres; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010012:Osteogenesis / Q000187:drug effects
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid; D000469:Alkaline Phosphatase