title: Promoting bioengineered tooth innervation using nanostructured and hybrid scaffolds.
abstract: The innervation of teeth mediated by axons originating from the trigeminal ganglia is essential for their function and protection. Immunosuppressive therapy using Cyclosporine A (CsA) was found to accelerate the innervation of transplanted tissues and particularly that of bioengineered teeth. To avoid the CsA side effects, we report in this study the preparation of CsA loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles, their embedding on polycaprolactone (PCL)-based scaffolds and their possible use as templates for the innervation of bioengineered teeth. This PCL scaffold, approved by the FDA and capable of mimicking the extracellular matrix, was obtained by electrospinning and decorated with CsA-loaded PLGA nanoparticles to allow a local sustained action of this immunosuppressive drug. Dental re-associations were co-implanted with a trigeminal ganglion on functionalized scaffolds containing PLGA and PLGA/cyclosporine in adult ICR mice during 2weeks. Histological analyses showed that the designed scaffolds did not alter the teeth development after in vivo implantation. The study of the innervation of the dental re-associations by indirect immunofluorescence and transmission electron microscopy (TEM), showed that 88.4% of the regenerated teeth were innervated when using the CsA-loaded PLGA scaffold. The development of active implants thus allows their potential use in the context of dental engineering.
  
  
  
  Tooth innervation is essential for their function and protection and this can be promoted in vivo using polymeric scaffolds functionalized with immunosuppressive drug-loaded nanoparticles. Immunosuppressive therapy using biodegradable nanoparticles loaded with Cyclosporine A was found to accelerate the innervation of bioengineered teeth after two weeks of implantation.
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative NanoMedicine Laboratory, FMTS, 11 rue Humann, Strasbourg, Strasbourg, France(1); Université de Strasbourg, Faculté de Chirurgie Dentaire, 1 place de l'Hôpital, Strasbourg F-67000, France. Electronic address: kuchler@unistra.fr.
authors.forename: S
authors.initials: S
authors.lastname: Kuchler-Bopp
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigación Biomédica en Red, C/ Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain; Department of Chemical and Environmental Engineering and Aragon Nanoscience Institute, University of Zaragoza, C/Mariano Esquillor, s/n, Zaragoza 50018, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Larrea
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative NanoMedicine Laboratory, FMTS, 11 rue Humann, Strasbourg, Strasbourg, France(1); Université de Strasbourg, Faculté de Chirurgie Dentaire, 1 place de l'Hôpital, Strasbourg F-67000, France.
authors.forename: L
authors.initials: L
authors.lastname: Petry
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative NanoMedicine Laboratory, FMTS, 11 rue Humann, Strasbourg, Strasbourg, France(1); Université de Strasbourg, Faculté de Chirurgie Dentaire, 1 place de l'Hôpital, Strasbourg F-67000, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Idoux-Gillet
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigación Biomédica en Red, C/ Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain; Department of Chemical and Environmental Engineering and Aragon Nanoscience Institute, University of Zaragoza, C/Mariano Esquillor, s/n, Zaragoza 50018, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Sebastian
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative NanoMedicine Laboratory, FMTS, 11 rue Humann, Strasbourg, Strasbourg, France(1); Université de Strasbourg, Faculté de Chirurgie Dentaire, 1 place de l'Hôpital, Strasbourg F-67000, France.
authors.forename: A
authors.initials: A
authors.lastname: Ferrandon
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative NanoMedicine Laboratory, FMTS, 11 rue Humann, Strasbourg, Strasbourg, France(1); Université de Strasbourg, Faculté de Chirurgie Dentaire, 1 place de l'Hôpital, Strasbourg F-67000, France.
authors.forename: P
authors.initials: P
authors.lastname: Schwinté
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigación Biomédica en Red, C/ Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain; Department of Chemical and Environmental Engineering and Aragon Nanoscience Institute, University of Zaragoza, C/Mariano Esquillor, s/n, Zaragoza 50018, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Arruebo
authors.affiliation: INSERM, UMR 1109, Osteoarticular and Dental Regenerative NanoMedicine Laboratory, FMTS, 11 rue Humann, Strasbourg, Strasbourg, France(1); Université de Strasbourg, Faculté de Chirurgie Dentaire, 1 place de l'Hôpital, Strasbourg F-67000, France.
authors.forename: N
authors.initials: N
authors.lastname: Benkirane-Jessel
mesh_terms: D000818:Animals; D057005:Bioengineering / Q000379:methods*; D016572:Cyclosporine / Q000494:pharmacology; D015921:Dental Implants; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry; D008813:Mice, Inbred ICR; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D054457:Tissue Scaffolds / Q000737:chemistry*; D014070:Tooth / Q000294:innervation*
chemical_list: D015921:Dental Implants; D011091:Polyesters; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D016572:Cyclosporine
keywords: Bioengineered tooth; Cyclosporine A; Electrospun polycaprolactone; Innervation; Nanoparticles