title: Calcium phosphates compounds in conjunction with hydrogel as carrier for BMP-2: a study on ectopic bone formation in rats.
abstract: Current treatment of fractures often involves the use of bone graft or bone morphogenetic proteins (BMP) to induce fracture healing, especially in patients with a compromised healing capacity. BMP has to be delivered in conjunction with a carrier. Unfortunately, there are drawbacks and limitations with current carriers, including their bovine origin which carries the risk of an immunological response. The physical properties also limit the use to open surgical procedures, as it cannot be injected. New carriers with improved properties are therefore needed. The aim of this study was to assess the ectopic bone forming capability of various calcium phosphate compounds when used in conjunction with a hydrogel as the carrier for BMP-2. Five different ceramic additives were tested, including β-tricalcium phosphate and four types of hydroxyapatite (HAP) (nanoHAP, HAP, clods of HAP >100 μm, and the biomimetic HAP Ostim35®). The compounds were injected into the thigh muscle of rats, where it formed a gel in situ. After 4 weeks bone formation was evaluated by peripheral quantitative computed tomography and histology. The major finding was that the 20 nm nanoHAP yielded a higher bone density than the other additives (P=0.0008, ANOVA with Tukey's multiple comparison test). We hypothesize that the higher bone density induced by nanoHAP might be due to nanocrystals of calcium phosphate acting as direct building blocks for biomineralization.
authors.affiliation: Uppsala University, Department of Orthopaedics, SE-751 85 Uppsala, Sweden. gry.hulsart@surgsci.uu.se
authors.forename: Gry
authors.initials: G
authors.lastname: Hulsart-Billström
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Hu
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Bergman
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Jonsson
authors.forename: Jonas
authors.initials: J
authors.lastname: Åberg
authors.forename: Ruikang
authors.initials: R
authors.lastname: Tang
authors.forename: Sune
authors.initials: S
authors.lastname: Larsson
authors.forename: Jöns
authors.initials: J
authors.lastname: Hilborn
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002130:Calcium Phosphates / Q000737:chemistry*; D002828:Choristoma / Q000000981:diagnostic imaging / Q000473:pathology*; D004337:Drug Carriers / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008297:Male; D008903:Minerals / Q000378:metabolism; D009132:Muscles / Q000000981:diagnostic imaging / Q000187:drug effects; D049329:Nanostructures / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014057:Tomography, X-Ray Computed
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D004337:Drug Carriers; D008903:Minerals; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D017886:Durapatite