title: Low dose BMP-2 treatment for bone repair using a PEGylated fibrinogen hydrogel matrix.
abstract: Bone repair strategies utilizing resorbable biomaterial implants aim to stimulate endogenous cells in order to gradually replace the implant with functional repair tissue. These biomaterials should therefore be biodegradable, osteoconductive, osteoinductive, and maintain their integrity until the newly formed host tissue can contribute proper function. In recent years there has been impressive clinical outcomes for this strategy when using osteoconductive hydrogel biomaterials in combination with osteoinductive growth factors such as human recombinant bone morphogenic protein (hrBMP-2). However, the success of hrBMP-2 treatments is not without risks if the factor is delivered too rapidly and at very high doses because of a suboptimal biomaterial. Therefore, the aim of this study was to evaluate the use of a PEGylated fibrinogen (PF) provisional matrix as a delivery system for low-dose hrBMP-2 treatment in a critical size maxillofacial bone defect model. PF is a semi-synthetic hydrogel material that can regulate the release of physiological doses of hrBMP-2 based on its controllable physical properties and biodegradation. hrBMP-2 release from the PF material and hrBMP-2 bioactivity were validated using in vitro assays and a subcutaneous implantation model in rats. Critical size calvarial defects in mice were treated orthotopically with PF containing 8 μg/ml hrBMP-2 to demonstrate the capacity of these bioactive implants to induce enhanced bone formation in as little as 6 weeks. Control defects treated with PF alone or left empty resulted in far less bone formation when compared to the PF/hrBMP-2 treated defects. These results demonstrate the feasibility of using a semi-synthetic biomaterial containing small doses of osteoinductive hrBMP-2 as an effective treatment for maxillofacial bone defects.
authors: Department of Anatomy and Cell Biology, Faculty of Medicine, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel. drorbd@tx.technion.ac.il
authors: Dror
authors: D
authors: Ben-David
authors: Samer
authors: S
authors: Srouji
authors: Keren
authors: K
authors: Shapira-Schweitzer
authors: Olga
authors: O
authors: Kossover
authors: Eran
authors: E
authors: Ivanir
authors: Gisela
authors: G
authors: Kuhn
authors: Ralph
authors: R
authors: Müller
authors: Dror
authors: D
authors: Seliktar
authors: Erella
authors: E
authors: Livne
mesh_terms: D000818:Animals; D001846:Bone Development; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000737:chemistry*; D020100:Hydrogels; D051379:Mice; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D019485:Bone Morphogenetic Proteins; D020100:Hydrogels; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D005340:Fibrinogen