title: Nanofibrous spongy microspheres enhance odontogenic differentiation of human dental pulp stem cells.
abstract: Dentin regeneration is challenging due to its complicated anatomical structure and the shortage of odontoblasts. In this study, a novel injectable cell carrier, nanofibrous spongy microspheres (NF-SMS), is developed for dentin regeneration. Biodegradable and biocompatible poly(l-lactic acid)-block-poly(l-lysine) are synthesized and fabricated into NF-SMS using self-assembly and thermally induced phase separation techniques. It is hypothesized that NF-SMS with interconnected pores and nanofibers can enhance the proliferation and odontogenic differentiation of human dental pulp stem cells (hDPSCs), compared to nanofibrous microspheres (NF-MS) without pore structure and conventional solid microspheres (S-MS) with neither nanofibers nor pore structure. During the first 9 d in culture, hDPSCs proliferate significantly faster on NF-SMS than on NF-MS or S-MS (p < 0.05). Following in vitro odontogenic induction, all the examined odontogenic genes (alkaline phosphatase content, osteocalcin, bone sialoprotein, collagen 1, dentin sialophosphoprotein (DSPP)), calcium content, and DSPP protein content are found significantly higher in the NF-SMS group than in the control groups. Furthermore, 6 weeks after subcutaneous injection of hDPSCs and microspheres into nude mice, histological analysis shows that NF-SMS support superior dentin-like tissue formation compared to NF-MS or S-MS. Taken together, NF-SMS have great potential as an injectable cell carrier for dentin regeneration.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, P. R. China.|Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Kuang
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Zhanpeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Gupte
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, P. R. China.
authors.forename: Longxing
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
mesh_terms: D000293:Adolescent; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002454:Cell Differentiation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D003804:Dentin / Q000502:physiology; D006801:Humans; D007279:Injections, Subcutaneous; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008863:Microspheres; D057139:Nanofibers / Q000737:chemistry*; D009805:Odontogenesis; D011108:Polymers / Q000737:chemistry; D012038:Regeneration; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D001672:Biocompatible Materials; D011108:Polymers
keywords: dental pulp; dentin regeneration; differentiation; microsphere; proliferation; stem cells