title: Bone reservoir: Injectable hyaluronic acid hydrogel for minimal invasive bone augmentation.
abstract: A strategy has been designed to develop hyaluronic acid (HA) hydrogel for in vivo bone augmentation using minimal invasive technique. A mild synthetic procedure was developed to prepare aldehyde modified HA by incorporating an amino-glycerol side chain via amidation reaction and selective oxidation of the pendent group. This modification, upon mixing with hydrazide modified HA formed hydrazone-crosslinked hydrogel within 30s that was stable at physiological pH. In vitro experiments showed no cytotoxicity of hydrogel with the controlled release of active bone morphogenic protein-2 (BMP-2). In vivo evaluation of this gel as a BMP-2 carrier was performed by injecting gels over the rat calvarium and showed bone formation in 8 weeks in correlation with the amount of BMP-2 loaded (0, 1 and 30μg) within the gel. Furthermore, hydrogels with 30μg of BMP-2 induced less bone formation upon subcutaneous injection in comparison with subperiosteal implantation. Histological examination showed newly formed bone with a high expression of osteocalcin, osteopontin and with angiogenic bone marrow when higher BMP-2 concentration was employed. Our result suggests that novel HA hydrogels could be used as a BMP-2 carrier and can promote bone augmentation for potential orthopedic applications.
authors.affiliation: Departamento de Anatomía y Embriología Humana I, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Martínez-Sanz
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Ossipov
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
authors.forename: Sune
authors.initials: S
authors.lastname: Larsson
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Jonsson
authors.forename: Oommen P
authors.initials: OP
authors.lastname: Varghese
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002460:Cell Line; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D006835:Hydrazones / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D007267:Injections; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D000447:Aldehydes; D055396:Bone Morphogenetic Protein 2; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D006835:Hydrazones; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid