title: Guided bone regeneration is promoted by the molecular events in the membrane compartment.
abstract: The working hypothesis of guided bone regeneration (GBR) is that the membrane physically excludes non-osteogenic tissues from interfering with bone healing. However, the underlying mechanisms are insufficiently explained. This study aimed to investigate the molecular and structural pattern of bone healing in trabecular bone defects, with and without naturally derived resorbable membrane. Defects were created in rat femurs and treated with the membrane or left empty (sham). After 3d, 6d and 28d, the defect sites and membranes were harvested and analyzed with histology, histomorphometry, quantitative-polymerase chain reaction (qPCR), Western blot (WB) and immunohistochemistry (IHC). Histomorphometry demonstrated that the presence of the membrane promoted bone formation in early and late periods. This was in parallel with upregulation of cell recruitment and coupled bone remodeling genes in the defect. Cells recruited into the membrane expressed signals for bone regeneration (BMP-2, FGF-2, TGF-β1 and VEGF). Whereas the native membrane contained FGF-2 but not BMP-2, an accumulation of FGF-2 and BMP-2 proteins and immunoreactive cells were demonstrated by WB and IHC in the in vivo implanted membrane. The results provide cellular and molecular evidence suggesting a novel role for the membrane during GBR, by acting as a bioactive compartment rather than a passive barrier.
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden; The Brånemark Clinic, Institute of Odontology, Public Dental Health Care, Gothenburg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Alberto
authors.initials: A
authors.lastname: Turri
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Elgali
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Forugh
authors.initials: F
authors.lastname: Vazirisani
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Johansson
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Emanuelsson
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden; Department of Oral, Maxillofacial Surgery and Research and Development, NU-Hospital Organization, Trollhättan, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Dahlin
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden. Electronic address: peter.thomsen@biomaterials.gu.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomsen
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Omar
authors.initials: O
authors.lastname: Omar
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001861:Bone Regeneration / Q000235:genetics*; D016723:Bone Remodeling; D001862:Bone Resorption / Q000150:complications / Q000235:genetics / Q000473:pathology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005269:Femur / Q000473:pathology; D005786:Gene Expression Regulation; D048091:Guided Tissue Regeneration / Q000379:methods*; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000473:pathology; D008297:Male; D008566:Membranes; D010012:Osteogenesis; D017207:Rats, Sprague-Dawley; D034421:Sus scrofa; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D018925:Chemokines
keywords: Gene expression; Guided bone regeneration; Histomorphometry; In vivo; Membrane; Western blot