title: Nanostructured assemblies for dental application.
abstract: Millions of teeth are saved each year by root canal therapy. Although current treatment modalities offer high levels of success for many conditions, an ideal form of therapy might consist of regenerative approaches in which diseased or necrotic pulp tissues are removed and replaced with healthy pulp tissue to revitalize teeth. Melanocortin peptides (alpha-MSH) possess anti-inflammatory properties in many acute and chronic inflammatory models. Our recent studies have shown that alpha-MSH covalently coupled to poly-l-glutamic acid (PGA-alpha-MSH) retains anti-inflammatory properties on rat monocytes. This study aimed to define the effects of PGA-alpha-MSH on dental pulp fibroblasts. Lipopolysaccharide (LPS)-stimulated fibroblasts incubated with PGA-alpha-MSH showed an early time-dependent inhibition of TNF-alpha, a late induction of IL-10, and no effect on IL-8 secretion. However, in the absence of LPS, PGA-alpha-MSH induced IL-8 secretion and proliferation of pulp fibroblasts, whereas free alpha-MSH inhibited this proliferation. Thus, PGA-alpha-MSH has potential effects in promoting human pulp fibroblast adhesion and cell proliferation. It can also reduce the inflammatory state of LPS-stimulated pulp fibroblasts observed in gram-negative bacterial infections. These effects suggest a novel use of PGA-alpha-MSH as an anti-inflammatory agent in the treatment of endodontic lesions. To better understand these results, we have also used the multilayered polyelectrolyte films as a reservoir for PGA-alpha-MSH by using not only PLL (poly-l-lysine) but also the Dendri Graft poly-l-lysines (DGL(G4)) to be able to adsorb more PGA-alpha-MSH. Our results indicated clearly that, by using PGA-alpha-MSH, we increase not only the viability of cells but also the proliferation. We have also analyzed at the nanoscale by atomic force microscopy these nanostructured architectures and shown an increase of thickness and roughness in the presence of PGA-alpha-MSH incorporated into the multilayered film (PLL-PGA-alpha-MSH)(10) or (DGL(G4)-PGA-alpha-MSH)(10) in accordance with the increase of the proliferation of the cells growing on the surface of these architectures. We report here the first use of nanostructured and functionalized multilayered films containing alpha-MSH as a new active biomaterial for endodontic regeneration.
authors.affiliation: Institut National de la Sante et de la Recherche Medicale (INSERM), Unite 977, 11 rue Humann, Strasbourg, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Fioretti
authors.forename: Carlos
authors.initials: C
authors.lastname: Mendoza-Palomares
authors.forename: Marie
authors.initials: M
authors.lastname: Helms
authors.forename: Denise
authors.initials: D
authors.lastname: Al Alam
authors.forename: Ludovic
authors.initials: L
authors.lastname: Richert
authors.forename: Youri
authors.initials: Y
authors.lastname: Arntz
authors.forename: Simon
authors.initials: S
authors.lastname: Rinckenbach
authors.forename: Fabien
authors.initials: F
authors.lastname: Garnier
authors.forename: Youssef
authors.initials: Y
authors.lastname: Haïkel
authors.forename: Sophie C
authors.initials: SC
authors.lastname: Gangloff
authors.forename: Nadia
authors.initials: N
authors.lastname: Benkirane-Jessel
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure*; D011099:Polyglutamic Acid / Q000737:chemistry*; D000521:alpha-MSH / Q000008:administration & dosage*
chemical_list: D053769:Nanocapsules; D011099:Polyglutamic Acid; D000521:alpha-MSH