title: A new heterologous fibrin sealant as scaffold to recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins for the repair of tibial bone defects.
abstract: Tissue engineering has special interest in bone tissue aiming at future medical applications Studies have focused on recombinant human bone morphogenetic protein-2 (rhBMP-2) and natural latex proteins due to the osteogenic properties of rhBMP-2 and the angiogenic characteristic of fraction 1 protein (P-1) extracted from the rubber tree Hevea brasiliensis. Furthermore, heterologous fibrin sealant (FS) has been shown as a promising alternative in regenerative therapies. The aim of this study was to evaluate these substances for the repair of bone defects in rats. A bone defect measuring 3mm in diameter was created in the proximal metaphysis of the left tibia of 60 rats and was implanted with rhBMP-2 or P-1 in combination with a new heterologous FS derived from snake venom. The animals were divided into six groups: control (unfilled bone defect), rhBMP-2 (defect filled with 5μg rhBMP-2), P-1 (defect filled with 5μg P-1), FS (defect filled with 8μg FS), FS/rhBMP-2 (defect filled with 8μg FS and 5μg rhBMP-2), FS/P-1 (defect filled with 8μg FS and 5μg P-1). The animals were sacrificed 2 and 6 weeks after surgery. The newly formed bone projected from the margins of the original bone and exhibited trabecular morphology and a disorganized arrangement of osteocyte lacunae. Immunohistochemical analysis showed intense expression of osteocalcin in all groups. Histometric analysis revealed a significant difference in all groups after 2 weeks (p<0.05), except for the rhBMP-2 and FS/rhBMP-2 groups (p>0.05). A statistically significant difference (p<0.05) was observed in all groups after 6 weeks in relation to the volume of newly formed bone in the surgical area. In conclusion, the new heterologous fibrin sealant was found to be biocompatible and the combination with rhBMP-2 showed the highest osteogenic and osteoconductive capacity for bone healing. These findings suggest a promising application of this combination in the regeneration surgery.
authors.affiliation: Department of Morphology and Pathology, School of Medicine of Jundiaí, Rua Francisco Telles, 250, Vila Arens, Cx. Postal 1295, Jundiaí CEP: 13202-550, SP, Brazil.
authors.forename: Eduardo Gomes
authors.initials: EG
authors.lastname: Machado
authors.affiliation: Department of Morphology, Stomatology and Physiology, Dental School of Ribeirão Preto, University of São Paulo, Avenida do Café S/N, Monte Alegre, Ribeirão Preto CEP: 14040-904, SP, Brazil.
authors.forename: João Paulo Mardegan
authors.initials: JP
authors.lastname: Issa
authors.affiliation: Department of Morphology, Stomatology and Physiology, Dental School of Ribeirão Preto, University of São Paulo, Avenida do Café S/N, Monte Alegre, Ribeirão Preto CEP: 14040-904, SP, Brazil.
authors.forename: Fellipe Augusto Tocchini de
authors.initials: FA
authors.lastname: Figueiredo
authors.affiliation: Department of Morphology and Pathology, School of Medicine of Jundiaí, Rua Francisco Telles, 250, Vila Arens, Cx. Postal 1295, Jundiaí CEP: 13202-550, SP, Brazil.
authors.forename: Geovane Ribeiro Dos
authors.initials: GR
authors.lastname: Santos
authors.affiliation: Department of Morphology and Pathology, School of Medicine of Jundiaí, Rua Francisco Telles, 250, Vila Arens, Cx. Postal 1295, Jundiaí CEP: 13202-550, SP, Brazil.
authors.forename: Ewerton Alexandre
authors.initials: EA
authors.lastname: Galdeano
authors.affiliation: Department of Morphology and Pathology, School of Medicine of Jundiaí, Rua Francisco Telles, 250, Vila Arens, Cx. Postal 1295, Jundiaí CEP: 13202-550, SP, Brazil.
authors.forename: Mariana Carla
authors.initials: MC
authors.lastname: Alves
authors.affiliation: Department of Morphology and Pathology, School of Medicine of Jundiaí, Rua Francisco Telles, 250, Vila Arens, Cx. Postal 1295, Jundiaí CEP: 13202-550, SP, Brazil.
authors.forename: Erivelto Luis
authors.initials: EL
authors.lastname: Chacon
authors.affiliation: Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Rua José Barbosa de Barros, 1780, Fazenda Experimental Lageado, Botucatu CEP: 18.610-307, SP, Brazil. Electronic address: cevap@cevap.unesp.br.
authors.forename: Rui Seabra
authors.initials: RS
authors.lastname: Ferreira Junior
authors.affiliation: Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Rua José Barbosa de Barros, 1780, Fazenda Experimental Lageado, Botucatu CEP: 18.610-307, SP, Brazil.
authors.forename: Benedito
authors.initials: B
authors.lastname: Barraviera
authors.affiliation: Department of Morphology and Pathology, School of Medicine of Jundiaí, Rua Francisco Telles, 250, Vila Arens, Cx. Postal 1295, Jundiaí CEP: 13202-550, SP, Brazil. Electronic address: cunhamr@hotmail.com.
authors.forename: Marcelo Rodrigues da
authors.initials: MR
authors.lastname: Cunha
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D001861:Bone Regeneration; D018786:Bone Substitutes / Q000627:therapeutic use*; D005260:Female; D005337:Fibrin / Q000627:therapeutic use*; D006801:Humans; D007840:Latex / Q000737:chemistry; D010940:Plant Proteins / Q000627:therapeutic use*; D017208:Rats, Wistar; D013977:Tibia / Q000473:pathology / Q000503:physiopathology; D023822:Tissue Engineering
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D007840:Latex; D010940:Plant Proteins; D005337:Fibrin
keywords: BMP-2; Fibrin; Natural latex; Protein P-1; Scaffold; Sealant