title: Influence of nanotopography on periodontal ligament stem cell functions and cell sheet based periodontal regeneration.
abstract: Periodontal regeneration is an important part of regenerative medicine, with great clinical significance; however, the effects of nanotopography on the functions of periodontal ligament (PDL) stem cells (PDLSCs) and on PDLSC sheet based periodontal regeneration have never been explored. Titania nanotubes (NTs) layered on titanium (Ti) provide a good platform to study this. In the current study, the influence of NTs of different tube size on the functions of PDLSCs was observed. Afterward, an ectopic implantation model using a Ti/cell sheets/hydroxyapatite (HA) complex was applied to study the effect of the NTs on cell sheet based periodontal regeneration. The NTs were able to enhance the initial PDLSC adhesion and spread, as well as collagen secretion. With the Ti/cell sheets/HA complex model, it was demonstrated that the PDLSC sheets were capable of regenerating the PDL tissue, when combined with bone marrow mesenchymal stem cell (BMSC) sheets and HA, without the need for extra soluble chemical cues. Simultaneously, the NTs improved the periodontal regeneration result of the ectopically implanted Ti/cell sheets/HA complex, giving rise to functionally aligned collagen fiber bundles. Specifically, much denser collagen fibers, with abundant blood vessels as well as cementum-like tissue on the Ti surface, which well-resembled the structure of natural PDL, were observed in the NT5 and NT10 sample groups. Our study provides the first evidence that the nanotopographical cues obviously influence the functions of PDLSCs and improve the PDLSC sheet based periodontal regeneration size dependently, which provides new insight to the periodontal regeneration. The Ti/cell sheets/HA complex may constitute a good model to predict the effect of biomaterials on periodontal regeneration.
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China ; Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China ; Department of Stomatology, PLA 309th Hospital, Beijing, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China ; Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Lingzhou
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China ; Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry; D001854:Bone Marrow Cells / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D017886:Durapatite / Q000737:chemistry; D005786:Gene Expression Regulation; D006801:Humans; D043942:Nanotubes / Q000737:chemistry*; D010513:Periodontal Ligament / Q000166:cytology* / Q000378:metabolism; D012038:Regeneration; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014025:Titanium / Q000737:chemistry; D055815:Young Adult
chemical_list: D001672:Biocompatible Materials; D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D024061:Collagen Type III; C512835:POSTN protein, human; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; C009495:titanium dioxide; D017886:Durapatite; D014025:Titanium; D000469:Alkaline Phosphatase
keywords: cell sheets; periodontal ligament stem cells; periodontal regeneration; titania nanotubes; titanium implant