title: A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone.
abstract: In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm(3)) as compared to rhBMP-2 alone (10.9 ± 2.1 mm(3)) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone.
authors.affiliation: Department of Orthopedics, Clinical Sciences, Lund, Lund University, Lund, 221 85, Sweden.|Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, 208016, India.
authors.forename: Deepak Bushan
authors.initials: DB
authors.lastname: Raina
authors.affiliation: Department of Orthopedics, Clinical Sciences, Lund, Lund University, Lund, 221 85, Sweden.|Department of Biomedical Engineering, Lund University, Lund, 221 85, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Isaksson
authors.affiliation: Department of Orthopedic Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, 2100, Denmark.
authors.forename: Werner
authors.initials: W
authors.lastname: Hettwer
authors.affiliation: Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, 208016, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Orthopedics, Clinical Sciences, Lund, Lund University, Lund, 221 85, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lidgren
authors.affiliation: Department of Orthopedics, Clinical Sciences, Lund, Lund University, Lund, 221 85, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Tägil
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000378:metabolism*; D002133:Calcium Sulfate / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage*; D017886:Durapatite / Q000008:administration & dosage*; D007093:Imidazoles / Q000008:administration & dosage / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D000077211:Zoledronic Acid
chemical_list: C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D011994:Recombinant Proteins; D000077211:Zoledronic Acid; D017886:Durapatite; D002133:Calcium Sulfate