Photobiomodulation of mesenchymal stem cells encapsulated in an injectable rhBMP4-loaded hydrogel directs hard tissue bioengineering

J Cell Physiol. 2018 Jun;233(6):4907-4918. doi: 10.1002/jcp.26309. Epub 2018 Jan 15.


Photobiomodulation (PBM) therapy displays relevant properties for tissue healing and regeneration, which may be of interest for the tissue engineering field. Here, we show that PBM is able to improve cell survival and to interact with recombinant human Bone Morphogenetic Protein 4 (rhBMP4) to direct and accelerate odonto/osteogenic differentiation of dental derived mesenchymal stem cells (MSCs). MSCs were encapsulated in an injectable and thermo-responsive cell carrier (Pluronic® F-127) loaded with rhBMP4 and then photoactivated. PBM improved MSCs self-renewal and survival upon encapsulation in the Pluronic® F-127. In the presence of rhBMP4, cell odonto/osteogenic differentiation was premature and markedly improved in the photoactivated MSCs. An in vivo calvarial critical sized defect model demonstrated significant increase in bone formation after PBM treatment. Finally, a balance in the reactive oxygen species levels may be related to the favorable results of PBM and rhBMP4 association. PBM may act in synergism with rhBMP4 and is a promise candidate to direct and accelerate hard tissue bioengineering.

Keywords: hydrogel; laser phototherapy; mesenchymal stem cell; photobiomodulation; pluronic® F-127; recombinant human bone morphogenetic protein 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Bone Morphogenetic Protein 4 / administration & dosage*
  • Bone Morphogenetic Protein 4 / chemistry
  • Bone Regeneration
  • Cell Differentiation / drug effects
  • Cell Differentiation / radiation effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cell Self Renewal / drug effects
  • Cell Self Renewal / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cells, Cultured
  • Drug Carriers*
  • Humans
  • Hydrogels
  • Injections
  • Lasers, Semiconductor
  • Low-Level Light Therapy / instrumentation
  • Low-Level Light Therapy / methods*
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / radiation effects*
  • Mice, Nude
  • NF-kappa B / metabolism
  • Osteogenesis / drug effects
  • Osteogenesis / radiation effects
  • Parietal Bone / injuries
  • Parietal Bone / pathology
  • Parietal Bone / surgery
  • Poloxamer / chemistry*
  • Reactive Oxygen Species / metabolism
  • Time Factors
  • Tissue Engineering / methods*
  • Tissue Scaffolds*
  • Young Adult


  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • Drug Carriers
  • Hydrogels
  • NF-kappa B
  • Reactive Oxygen Species
  • Poloxamer