Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells

Biomaterials. 2007 Apr;28(10):1830-7. doi: 10.1016/j.biomaterials.2006.11.050. Epub 2007 Jan 8.


Acrylated hyaluronic acid (HA) was used as a scaffold for bone morphogenic protein-2 (BMP-2) and human mesenchymal stem cells (hMSCs) for rat calvarial defect regeneration. HA was acrylated by two-step reactions: (1) introduction of an amine group using adipic acid dihydrazide (ADH); (2) acrylation by N-acryloxysuccinimide. Tetrathiolated poly(ethylene) glycol (PEG-SH(4)) was used as a cross-linker by a Michael-type addition reaction and the hydrogel was formed within 10min under physiological conditions. This hydrogel is degraded completely by 100U/ml hyaluronidase in vitro. hMSCs and/or BMP-2 was added during gelation. Cellular viability in vitro was increased up to 55% in the hydrogels with BMP-2 compared with the control. For in vivo calvarial defect regeneration, five different samples (i.e., control, hydrogel, hydrogel with BMP-2, hydrogel with MSCs, and hydrogel with BMP-2 and MSCs) were implanted for 4 weeks. The histological results demonstrated that the hydrogels with BMP-2 and MSCs had the highest expression of osteocalcin and mature bone formation with vascular markers, such as CD31 and vascular endothelial growth factors, compared with the other samples. This study demonstrated that HA base hydrogel can be used for cell and growth factor carriers for tissue regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / administration & dosage*
  • Bone Regeneration / physiology*
  • Cell Culture Techniques / methods
  • Combined Modality Therapy
  • Drug Carriers / chemistry*
  • Hyaluronic Acid / chemistry*
  • Hydrogels / chemistry
  • Male
  • Materials Testing
  • Mesenchymal Stem Cell Transplantation / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Skull Fractures / drug therapy*
  • Skull Fractures / pathology
  • Skull Fractures / surgery*
  • Transforming Growth Factor beta / administration & dosage*
  • Treatment Outcome


  • BMP2 protein, human
  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Drug Carriers
  • Hydrogels
  • Transforming Growth Factor beta
  • Hyaluronic Acid