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

Jungju Kim, In Sook Kim, Tae Hyung Cho, Kyu Back Lee, Soon Jung Hwang, Giyoong Tae, Insup Noh, Sang Hoon Lee, Yongdoo Park, Kyung Sun

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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-SH4) was used as a cross-linker by a Michael-type addition reaction and the hydrogel was formed within 10 min under physiological conditions. This hydrogel is degraded completely by 100 U/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.

Original languageEnglish
Pages (from-to)1830-1837
Number of pages8
Issue number10
Publication statusPublished - 2007 Apr 1



  • Bone morphogenic protein
  • Bone regeneration
  • Hyaluronic acid
  • Hydrogel
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

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