title: Mandibular Jaw Bone Regeneration Using Human Dental Cell-Seeded Tyrosine-Derived Polycarbonate Scaffolds.
abstract: Here we present a new model for alveolar jaw bone regeneration, which uses human dental pulp cells (hDPCs) combined with tyrosine-derived polycarbonate polymer scaffolds [E1001(1k)] containing beta-tricalcium phosphate (β-TCP) [E1001(1k)/β-TCP]. E1001(1k)/β-TCP scaffolds (5 mm diameter × 1 mm thickness) were fabricated to fit a 5 mm rat mandibular ramus critical bone defect. Five experimental groups were examined in this study: (1) E1001(1k)/β-TCP scaffolds seeded with a high density of hDPCs, 5.0 × 10(5) hDPCs/scaffold (CH); (2) E1001(1k)/β-TCP scaffolds seeded with a lower density of hDPCs, 2.5 × 10(5) hDPCs/scaffold (CL); (3) acellular E1001(1k)/β-TCP scaffolds (SA); (4) acellular E1001(1k)/β-TCP scaffolds supplemented with 4 μg recombinant human bone morphogenetic protein-2 (BMP); and (5) empty defects (EDs). Replicate hDPC-seeded and acellular E1001(1k)/β-TCP scaffolds were cultured in vitro in osteogenic media for 1 week before implantation for 3 and 6 weeks. Live microcomputed tomography (μCT) imaging at 3 and 6 weeks postimplantation revealed robust bone regeneration in the BMP implant group. CH and CL groups exhibited similar uniformly distributed mineralized tissue coverage throughout the defects, but less than the BMP implants. In contrast, SA-treated defects exhibited sparse areas of mineralized tissue regeneration. The ED group exhibited slightly reduced defect size. Histological analyses revealed no indication of an immune response. In addition, robust expression of dentin and bone differentiation marker expression was observed in hDPC-seeded scaffolds, whereas, in contrast, BMP and SA implants exhibited only bone and not dentin differentiation marker expression. hDPCs were detected in 3-week but not in 6-week hDPC-seeded scaffold groups, indicating their survival for at least 3 weeks. Together, these results show that hDPC-seeded E1001(1k)/β-TCP scaffolds support the rapid regeneration of osteo-dentin-like mineralized jaw tissue, suggesting a promising new therapy for alveolar jaw bone repair and regeneration.
authors.affiliation: 1 Department of Orthodontics, Division of Craniofacial and Molecular Genetics, Tufts University School of Dental Medicine , Boston, Massachusetts.
authors.forename: Weibo
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 2 New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey , Piscataway, New Jersey.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 2 New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey , Piscataway, New Jersey.
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.affiliation: 2 New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey , Piscataway, New Jersey.
authors.forename: Lauren
authors.initials: L
authors.lastname: Macri
authors.affiliation: 2 New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey , Piscataway, New Jersey.
authors.forename: Joachim
authors.initials: J
authors.lastname: Kohn
authors.affiliation: 1 Department of Orthodontics, Division of Craniofacial and Molecular Genetics, Tufts University School of Dental Medicine , Boston, Massachusetts.
authors.forename: Pamela C
authors.initials: PC
authors.lastname: Yelick
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D003782:Dental Pulp / Q000378:metabolism*; D005260:Female; D006801:Humans; D008334:Mandible / Q000378:metabolism* / Q000473:pathology; D008338:Mandibular Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010012:Osteogenesis; D011076:Polycarboxylate Cement / Q000737:chemistry*; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D011076:Polycarboxylate Cement; C005506:polycarbonate; D014443:Tyrosine