title: Evaluation of collagen/heparin coated TCP/HA granules for long-term delivery of BMP-2.
abstract: Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth factors. However, a delivery system is essential to take advantage of the osteoinductive effect of BMPs. The purpose of this study was to develop a sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP-2). We covalently attached heparin to a cross-linked collagen type I coated tricalciumphosphate/hydroxyapatite (TCP/HA) bone substitute and subsequently loaded it with BMP-2. To systematically evaluate the contribution of each component with respect to the binding and release of BMP-2, six constructs were prepared and characterized: TCP/HA, TCP/HA with collagen (TCP/HACol), and TCP/HA with collagen and heparin (TCP/HAColHep) with and without BMP-2 (B). More BMP-2 bound to the TCP/HAColHep + B (92.9 ± 4.8 ng BMP-2/mg granule) granules as compared to the TCP/HACol + B (69.0 ± 9.6 ng BMP-2/mg granule) and TCP/HA + B granules (62.9 ± 5.4 ng BMP-2/mg granule). No difference in release pattern was found between the TCP/HA + B and TCP/HACol + B granules. Up to day 14, BMP-2 was still bound to the TCP/HAColHep + B granules, whereas most BMP had been released from TCP/HACol + B and TCP/HA + B granules at that time. After 21 days most BMP-2 also had been released from the TCP/HAColHep + B granules. The local and sustained delivery system for BMP-2 developed in this study may be useful as a carrier for BMP-2 and could possibly enhance bone regeneration efficacy for the treatment of large bone defects.
authors.affiliation: Orthopedic Research Laboratory, Department of Orthopedics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. g.hannink@orthop.umcn.nl
authors.forename: Gerjon
authors.initials: G
authors.lastname: Hannink
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Geutjes
authors.forename: Willeke F
authors.initials: WF
authors.lastname: Daamen
authors.forename: Pieter
authors.initials: P
authors.lastname: Buma
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018786:Bone Substitutes / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D016466:CHO Cells; D002130:Calcium Phosphates / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D003094:Collagen / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006493:Heparin; D003094:Collagen; D017886:Durapatite; C018392:tricalcium phosphate