title: Injectable rhBMP-2-loaded chitosan hydrogel composite: osteoinduction at ectopic site and in segmental long bone defect.
abstract: Carriers for bone morphogenetic protein-2 (BMP-2) used in clinical practice still suffer from limitations such as insufficient protein retention. In addition, there is a clinical need for injectable carriers. The main objective of this study was to assess bone forming ability of rhBMP-2 combined either with chitosan hydrogel (rhBMP-2/CH) or chitosan hydrogel containing β-tricalcium phosphate (β-TCP) (rhBMP-2/CH/TCP). Formulations were first compared in a rat ectopic intramuscular bone formation model, and the optimal formulation was further evaluated in healing of 15-mm critical size defect in the radius of a rabbit. Three weeks after injection ectopically formed bone was analyzed by microcomputerized tomography (micro-CT) and histology. Significantly higher (4.7-fold) mineralized bone formation was observed in the rhBMP-2/CH/TCP group compared to rhBMP-2/CH group. In a pilot study, defect in a rabbit radius treated with rhBMP-2/CH/TCP showed incomplete regeneration at 8 weeks with composite leakage from the defect, indicating the need for formulation refinement when segmental defect repair is foreseen.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Luca
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Rougemont
authors.forename: Beat H
authors.initials: BH
authors.lastname: Walpoth
authors.forename: Ludovic
authors.initials: L
authors.lastname: Boure
authors.forename: Andrea
authors.initials: A
authors.lastname: Tami
authors.forename: James M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Olivier
authors.initials: O
authors.lastname: Jordan
authors.forename: Robert
authors.initials: R
authors.lastname: Gurny
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry* / Q000494:pharmacology*; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D002130:Calcium Phosphates / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D007267:Injections; D008297:Male; D008422:Materials Testing; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D004337:Drug Carriers; D020100:Hydrogels; C485817:beta-tricalcium phosphate; D048271:Chitosan