title: The effects of fibrinogen concentration on fibrin/atelocollagen composite gel: an in vitro and in vivo study in rabbit calvarial bone defect.
abstract: OBJECTIVE
  This study aimed to optimize the fibrinogen concentration in fibrin and atelocollagen (AT-COL) (fibrin/AT-COL) composite gel for improving bone regeneration.
  
  
  METHODS
  The fibrin/AT-COL composite gels were fabricated using various fibrinogen concentrations, and the microstructure and mechanical properties of the resulting composite gels analyzed. The cytocompatibility of the composite gels was examined using human mesenchymal stem cell (hMSCs). Furthermore, in nine rabbits, the in vivo bone regeneration efficiency was evaluated using a rabbit calvarial defects model at 2 weeks (n = 3), 4 weeks (n = 3), and 8 weeks (n = 3).
  
  
  RESULTS
  Scanning electron microscopy analysis revealed the formation of a fibrin layer matrix and collagen fibril networks. The composite gel containing 40 mg/ml fibrinogen showed a densely packed fibrin matrix and displayed superior mechanical properties. Cells cultured in the composite gels prepared with 5-20 mg/ml fibrinogen appeared elongated, with a spindle-like morphology. At a higher fibrinogen concentration (40 mg/ml), many cells were rounded and showed limited viability. In an in vivo study, at 8 weeks, the volume of fibrin/AT-COL gel (P = 0.02) was significantly higher than that of fibrin gel alone in the newly formed bone. Histological analysis revealed more islands of newly formed bone filling the central area of the defect in the fibrin/AT-COL gel-implanted animals.
  
  
  CONCLUSIONS
  Our results demonstrate that optimization of the fibrinogen content of fibrin/AT-COL composites should be beneficial for bone tissue engineering.
authors.affiliation: Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, Korea.|Bonecell Biotech Inc., Daejeon, Korea.
authors.forename: Beom-Su
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, School of Medicine, Wonkwang University, Iksan, Korea.
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Dentistry, Oral and Maxillofacial, Wonkwang University, Iksan, Korea.
authors.forename: Jung-Goo
authors.initials: JG
authors.lastname: Choi
authors.affiliation: Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Korea.
authors.forename: Hyung-Keun
authors.initials: HK
authors.lastname: You
authors.affiliation: Wonkwang Bone Regeneration Research Institute, Wonkwang University, Iksan, Korea.|Department of Dentistry, Oral and Maxillofacial, Wonkwang University, Iksan, Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001861:Bone Regeneration; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D005337:Fibrin / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry; D005782:Gels / Q000737:chemistry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D011817:Rabbits; D012886:Skull; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D005782:Gels; C059821:atelocollagen; D005337:Fibrin; D005340:Fibrinogen; D003094:Collagen
keywords: atelocollagen; bone regeneration; fibrin; fibrinogen; stiffness