title: Nanogel-based scaffold delivery of prostaglandin E(2) receptor-specific agonist in combination with a low dose of growth factor heals critical-size bone defects in mice.
abstract: OBJECTIVE
  Regeneration of bone requires the combination of appropriate drugs and an appropriate delivery system to control cell behavior. However, the delivery of multiple drugs to heal bone is complicated by the availability of carriers. The aim of this study was to explore a new system for delivery of a selective EP4 receptor agonist (EP4A) in combination with low-dose bone morphogenetic protein 2 (BMP-2).
  
  
  METHODS
  Combined delivery of EP4A and BMP-2 was carried out with a nanogel-based scaffold in the shape of a disc, to repair critical-size circle-shaped bone defects in calvariae that otherwise did not heal spontaneously.
  
  
  RESULTS
  Combination treatment with EP4A and low-dose BMP-2 in nanogel efficiently activated bone cells to regenerate calvarial bone by forming both outer and inner cortical plates as well as bone marrow tissue to regenerate a structure similar to that of intact calvaria. EP4A enhanced low-dose BMP-2-induced cell differentiation and activation of transcription events in osteoblasts.
  
  
  CONCLUSIONS
  These data indicate that combined delivery of EP4A and low-dose BMP-2 via nanogel-based hydrogel provides a new system for bone repair.
authors.affiliation: Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Paksinee
authors.initials: P
authors.lastname: Kamolratanakul
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Hayata
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.forename: Aya
authors.initials: A
authors.lastname: Kawamata
authors.forename: Chikako
authors.initials: C
authors.lastname: Hayashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hemmi
authors.forename: Masashi
authors.initials: M
authors.lastname: Nagao
authors.forename: Ryo
authors.initials: R
authors.lastname: Hanyu
authors.forename: Takuya
authors.initials: T
authors.lastname: Notomi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamoto
authors.forename: Teruo
authors.initials: T
authors.lastname: Amagasa
authors.forename: Kazunari
authors.initials: K
authors.lastname: Akiyoshi
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001847:Bone Diseases / Q000188:drug therapy* / Q000503:physiopathology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000080385:Nanogels; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D011094:Polyethyleneimine / Q000494:pharmacology / Q000627:therapeutic use*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D051901:Smad4 Protein / Q000378:metabolism; D054457:Tissue Scaffolds
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D036341:Intercellular Signaling Peptides and Proteins; D000080385:Nanogels; D058309:Receptors, Prostaglandin E, EP4 Subtype; D051901:Smad4 Protein; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D000469:Alkaline Phosphatase