title: A uni-cortical femoral defect model in the rat: evaluation using injectable hyaluronan hydrogel as a carrier for bone morphogenetic protein-2.
abstract: The development of biomaterial for bone regeneration requires animal models that are reliable and designed to mimic clinically relevant situations. We have previously investigated hydrogels comprised of modified hyaluronic acid and polyvinyl alcohol in models of ectopic bone formation. This hydrogel induces bone regeneration when loaded with bone morphogenetic proteins (BMPs). To allow further optimization of hydrogels, we developed a new, femoral, non-critical-sized cortical defect model. In the rat femur, we drilled standardized, elongated unilateral cortical defects that did not require stabilization and that could be created bilaterally to allow paired comparisons of biomaterials. After optimizing the defect size, subsequent stress fractures occurred in only 8% and the defect healed partially over the 40 day study period. In a time-course experiment, we treated bone defects with the previously studied hyaluronan hydrogel loaded with 10 µg hydroxyapatite and 6 µg BMP-2. The shape of the defect allowed controlled containment of the material within the defect. The defect in the right leg was left untreated, while the left defect was filled with 40 µl of the BMP hydrogel. As determined by pQCT analysis, the treated defects had a higher bone mineral content, bone area and bone density than control defects. The relative difference was greatest between the groups at 10 and 20 days and diminished as the defect healed in the untreated legs. We conclude that this animal model allows facile and rapid screening of biomaterials for bone regeneration in cortical femoral defects without requiring external fixation.
authors.affiliation: Department of Surgical Sciences, Unit of Orthopaedics, Uppsala University, Uppsala, Sweden.
authors.forename: Gry
authors.initials: G
authors.lastname: Hulsart-Billström
authors.affiliation: Department of Materials Chemistry, Ångström Laboratory Uppsala University, Uppsala, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Bergman
authors.affiliation: Department of Surgical Sciences, Unit of Orthopaedics, Uppsala University, Uppsala, Sweden.
authors.forename: Brittmarie
authors.initials: B
authors.lastname: Andersson
authors.affiliation: Department of Materials Chemistry, Ångström Laboratory Uppsala University, Uppsala, Sweden.
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
authors.affiliation: Department of Surgical Sciences, Unit of Orthopaedics, Uppsala University, Uppsala, Sweden.
authors.forename: Sune
authors.initials: S
authors.lastname: Larsson
authors.affiliation: Department of Surgical Sciences, Unit of Orthopaedics, Uppsala University, Uppsala, Sweden.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Jonsson
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000494:pharmacology*; D005269:Femur / Q000293:injuries* / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D020100:Hydrogels; D006820:Hyaluronic Acid