title: Periodontal ligament stem/progenitor cells with protein-releasing scaffolds for cementum formation and integration on dentin surface.
abstract: Purpose/Aim: Cementogenesis is a critical step in periodontal tissue regeneration given the essential role of cementum in anchoring teeth to the alveolar bone. This study is designed to achieve integrated cementum formation on the root surfaces of human teeth using growth factor-releasing scaffolds with periodontal ligament stem/progenitor cells (PDLSCs).
  
  
  
  Human PDLSCs were sorted by CD146 expression, and characterized using CFU-F assay and induced multi-lineage differentiation. Polycaprolactone scaffolds were fabricated using 3D printing, embedded with poly(lactic-co-glycolic acids) (PLGA) microspheres encapsulating connective tissue growth factor (CTGF), bone morphogenetic protein-2 (BMP-2), or bone morphogenetic protein-7 (BMP-7). After removing cementum on human tooth roots, PDLSC-seeded scaffolds were placed on the exposed dentin surface. After 6-week culture with cementogenic/osteogenic medium, cementum formation and integration were evaluated by histomorphometric analysis, immunofluorescence, and qRT-PCR.
  
  
  
  Periodontal ligament (PDL) cells sorted by CD146 and single-cell clones show a superior clonogenecity and multipotency as compared with heterogeneous populations. After 6 weeks, all the growth factor-delivered groups showed resurfacing of dentin with a newly formed cementum-like layer as compared with control. BMP-2 and BMP-7 showed de novo formation of tissue layers significantly thicker than all the other groups, whereas CTGF and BMP-7 resulted in significantly improved integration on the dentin surface. The de novo mineralized tissue layer seen in BMP-7-treated samples expressed cementum matrix protein 1 (CEMP1). Consistently, BMP-7 showed a significant increase in CEMP1 mRNA expression.
  
  
  
  Our findings represent important progress in stem cell-based cementum regeneration as an essential part of periodontium regeneration.
authors.affiliation: a Regenerative Engineering Laboratory , Columbia University Medical Center , New York , NY , USA.
authors.forename: Hankyu
authors.initials: H
authors.lastname: Cho
authors.affiliation: a Regenerative Engineering Laboratory , Columbia University Medical Center , New York , NY , USA.
authors.forename: Solaiman
authors.initials: S
authors.lastname: Tarafder
authors.affiliation: a Regenerative Engineering Laboratory , Columbia University Medical Center , New York , NY , USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Fogge
authors.affiliation: a Regenerative Engineering Laboratory , Columbia University Medical Center , New York , NY , USA.
authors.forename: Kristy
authors.initials: K
authors.lastname: Kao
authors.affiliation: a Regenerative Engineering Laboratory , Columbia University Medical Center , New York , NY , USA.
authors.forename: Chang H
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002469:Cell Separation; D002999:Clone Cells; D055513:Connective Tissue Growth Factor / Q000494:pharmacology*; D003739:Dental Cementum / Q000166:cytology*; D003804:Dentin / Q000737:chemistry*; D006801:Humans; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology*; D011506:Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D014081:Tooth Extraction; D014092:Tooth Root / Q000166:cytology; D055815:Young Adult
chemical_list: D019485:Bone Morphogenetic Proteins; C510886:CEMP1 protein, human; D011506:Proteins; D055513:Connective Tissue Growth Factor
keywords: 3D printing; cementum; controlled delivery; periodontal ligament stem cells; regeneration