title: Bioinspired Collagen-Apatite Nanocomposites for Bone Regeneration.
abstract: BACKGROUND
  Natural bone has a complex hierarchical nanostructure composed of well-organized collagen fibrils embedded with apatite crystallites. Bone tissue engineering requires scaffolds with structural properties and functionality similar to the natural bone. Inspired by bone, a collagen-apatite (Col-Ap) nanocomposite was fabricated with bonelike subfibrillar nanostructures using a modified bottom-up biomimetic approach and has a potential role in the healing of large bone defects in unresolved apical periodontitis.
  
  
  METHODS
  The bone regeneration potential of the Col-Ap nanocomposite was investigated by comparing it with inorganic beta-tricalcium phosphate and organic pure collagen using a critical-sized rodent mandibular defect model. Micro-computed tomographic imaging and histologic staining were used to evaluate new bone formation in vivo.
  
  
  RESULTS
  When compared with the beta-tricalcium phosphate and collagen scaffolds, the Col-Ap nanocomposite scaffold exhibited superior regeneration properties characterized by profuse deposition of new bony structures and vascularization at the defect center. Immunohistochemistry showed that the transcription factor osterix and vascular endothelial growth factor receptor 1 were highly expressed in the Col-Ap group. The results indicate that the Col-Ap nanocomposite activates more bone-forming cells and stimulates more vascular tissue ingrowth. Furthermore, the Col-Ap nanocomposite induces extracellular matrix secretion and mineralization of rat bone marrow stem cells. The increased expression of transforming growth factor beta 1 may contribute to the formation of a mineralized extracellular matrix.
  
  
  CONCLUSIONS
  The present study lays the foundation for the development of Col-Ap nanocomposite-based bone grafts for future clinical applications in bone regeneration of large periapical lesions after apical curettage or apicoectomy.
authors.affiliation: Center for Craniofacial Stem Cell Research and Regeneration, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center for Craniofacial Stem Cell Research and Regeneration, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Center for Craniofacial Stem Cell Research and Regeneration, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Center for Craniofacial Stem Cell Research and Regeneration, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
authors.forename: Datong
authors.initials: D
authors.lastname: Chang
authors.affiliation: Department of Orthodontics, School of Stomatology, Zhengzhou University, Henan, People's Republic of China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Fu
authors.affiliation: Center for Craniofacial Stem Cell Research and Regeneration, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.
authors.forename: Gaonan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Center for Craniofacial Stem Cell Research and Regeneration, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China. Electronic address: orthoyan@bjmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia.
authors.forename: Franklin R
authors.initials: FR
authors.lastname: Tay
authors.affiliation: Center for Craniofacial Stem Cell Research and Regeneration, Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China. Electronic address: yanhengzhou@vip.163.com.
authors.forename: Yanheng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001031:Apatites / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D008334:Mandible; D053761:Nanocomposites / Q000737:chemistry*; D051381:Rats; D000076182:Sp7 Transcription Factor; D054457:Tissue Scaffolds; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D001031:Apatites; D002130:Calcium Phosphates; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C485817:beta-tricalcium phosphate; D003094:Collagen
keywords: Apatite; biomimetics; bone scaffold; collagen; histology; immunohistochemistry; in vivo; micro–computed tomography; nanocomposite