title: Cell engineering by the internalization of bioinstructive micelles for enhanced bone regeneration.
abstract: OBJECTIVE
  To direct precursor cells toward the osteoblastic lineage, by using an intracellular nanocarrier releasing dexamethasone.
  
  
  METHODS
  Biodegradable gelatin-based micelles entrapped dexamethasone (dex-micelles). Internalization efficiency and biocompatibility of dex-micelles and their potency for in vitro osteogenic differentiation and in vivo bone regeneration were assessed.
  
  
  RESULTS
  Dex-micelles were internalized by rat bone marrow mesenchymal stem cells and demonstrated a pH-responsive release profile and an enhancement of 2D and 3D in vitro osteogenic differentiation. In vivo implantation of gelatin scaffolds seeded with rat bone marrow mesenchymal stem cells precultured for 24 h with dex-micelles promoted a significant enhancement of de novo bone formation in a rat ulna defect, in a dose-dependent manner.
  
  
  CONCLUSIONS
  The proposed intracellular delivery system is a powerful tool to promote bone regeneration.
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Sakyo Ku, Kyoto 6068507, Japan.|3B's Research Group - Biomaterials, Biodegradables & Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering & Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Vítor E
authors.initials: VE
authors.lastname: Santo
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Sakyo Ku, Kyoto 6068507, Japan.
authors.forename: Juthamas
authors.initials: J
authors.lastname: Ratanavaraporn
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Sakyo Ku, Kyoto 6068507, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables & Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering & Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Manuela E
authors.initials: ME
authors.lastname: Gomes
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables & Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering & Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: João F
authors.initials: JF
authors.lastname: Mano
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables & Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering & Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal.|ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Sakyo Ku, Kyoto 6068507, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
mesh_terms: D000818:Animals; D063566:Biodegradable Plastics / Q000009:adverse effects / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D060846:Cell Engineering; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D008823:Micelles; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats
chemical_list: D063566:Biodegradable Plastics; D008823:Micelles; D003907:Dexamethasone
keywords: bone regeneration; intracellular delivery; mesenchymal stem cell; micelle; nanoparticle; tissue engineering