Effect of bone marrow-derived stem cells and bone morphogenetic protein-2 on treatment of osteoradionecrosis in a rat model

J Craniomaxillofac Surg. 2015 Oct;43(8):1478-86. doi: 10.1016/j.jcms.2015.06.035. Epub 2015 Jul 8.

Abstract

Purpose: We investigated the effect of rat mesenchymal stem cells (rMSCs) and bone morphogenetic protein-2 (BMP-2) on the osseous healing of osteoradionecrosis in the rat mandible, depending on application time.

Material and methods: One week after irradiation (30 Gy) on the right mandible, all molar teeth were extracted. In Group 1 (n = 25), rMSCs and/or BMP-2 carried with hydrogel were applied immediately after surgery. In Group 2 (n = 25), application was done 4 weeks after surgery, after the occurrence of osteoradionecrosis. No hydrogel (n = 5), hydrogel alone (n = 5), hydrogel with 2 × 10(4) rMSCs (n = 5), hydrogel with 10 μg of BMP-2 (n = 5), or hydrogel with 10 μg of BMP-2 and 2 × 10(4) rMSCs (n = 5) was applied. Micro-CT data of bone healing were collected at 4 weeks post-application.

Results: In Group 1, BMP-2 was effective in increasing both bone volume (BV) and bone mineral density (BMD), whereas rMSCs were not. In Group 2, the combined application of rMSCs and BMP-2 significantly increased BMD and BV compared to values in the groups without hydrogel and with hydrogel alone.

Conclusion: Osseous healing after post-irradiation trauma in rats was enhanced immediately after dentoalveolar trauma by application of BMP-2, whereas the combined application of rMSCs and BMP-2 was most effective after osteoradionecrosis occurred.

Keywords: Bone marrow-derived stem cell; Bone morphogenetic protein-2; Osteoradionecrosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density / physiology
  • Bone Morphogenetic Protein 2 / therapeutic use*
  • Bone Regeneration / drug effects
  • Bone Regeneration / physiology*
  • Disease Models, Animal
  • Drug Carriers
  • Hyaluronic Acid / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Male
  • Mandibular Diseases / drug therapy
  • Mandibular Diseases / therapy*
  • Mesenchymal Stem Cells / physiology*
  • Organ Size
  • Osteoradionecrosis / drug therapy
  • Osteoradionecrosis / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Surgical Wound Dehiscence / drug therapy
  • Surgical Wound Dehiscence / therapy
  • Tissue Scaffolds / chemistry
  • Tooth Extraction
  • Tooth Socket / pathology
  • Wound Healing / drug effects
  • Wound Healing / physiology
  • X-Ray Microtomography / methods

Substances

  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Drug Carriers
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Hyaluronic Acid