title: Three-dimensional printed multiphase scaffolds for regeneration of periodontium complex.
abstract: Tooth-supporting periodontium forms a complex with multiple tissues, including cementum, periodontal ligament (PDL), and alveolar bone. In this study, we developed multiphase region-specific microscaffolds with spatiotemporal delivery of bioactive cues for integrated periodontium regeneration. Polycarprolactione-hydroxylapatite (90:10 wt%) scaffolds were fabricated using three-dimensional printing seamlessly in three phases: 100-μm microchannels in Phase A designed for cementum/dentin interface, 600-μm microchannels in Phase B designed for the PDL, and 300-μm microchannels in Phase C designed for alveolar bone. Recombinant human amelogenin, connective tissue growth factor, and bone morphogenetic protein-2 were spatially delivered and time-released in Phases A, B, and C, respectively. Upon 4-week in vitro incubation separately with dental pulp stem/progenitor cells (DPSCs), PDL stem/progenitor cells (PDLSCs), or alveolar bone stem/progenitor cells (ABSCs), distinctive tissue phenotypes were formed with collagen I-rich fibers especially by PDLSCs and mineralized tissues by DPSCs, PDLSCs, and ABSCs. DPSC-seeded multiphase scaffolds upon in vivo implantation yielded aligned PDL-like collagen fibers that inserted into bone sialoprotein-positive bone-like tissue and putative cementum matrix protein 1-positive/dentin sialophosphoprotein-positive dentin/cementum tissues. These findings illustrate a strategy for the regeneration of multiphase periodontal tissues by spatiotemporal delivery of multiple proteins. A single stem/progenitor cell population appears to differentiate into putative dentin/cementum, PDL, and alveolar bone complex by scaffold's biophysical properties and spatially released bioactive cues.
authors.affiliation: Center for Craniofacial Regeneration (CCR), Columbia University Medical Center , New York, New York.
authors.forename: Chang H
authors.initials: CH
authors.lastname: Lee
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hajibandeh
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Andrew
authors.initials: A
authors.lastname: Fan
authors.forename: Peng
authors.initials: P
authors.lastname: Shang
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Mao
mesh_terms: D000293:Adolescent; D000328:Adult; D053523:Amelogenin / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology; D006801:Humans; D051379:Mice; D010519:Periodontium / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D066330:Printing, Three-Dimensional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D055815:Young Adult
chemical_list: D053523:Amelogenin; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D003094:Collagen