Injectable tissue-engineered bone repair of a rat calvarial defect

Scott J. Stephan, Sunil S. Tholpady, Brian Gross, Caren E. Petrie-Aronin, Edward A. Botchway, Lakshmi S. Nair, Roy C. Ogle, Stephen S. Park

Research output: Contribution to journalArticle

86 Scopus citations


Objectives/Hypothesis: Advances in bone repair have focused on the minimally-invasive delivery of tissue-engineered bone (TEB). A promising injectable biopolymer of chitosan and inorganic phosphates was seeded with mesenchymal stem cells (MSCs) and a bone growth factor (BMP-2), and evaluated in a rat calvarial critical size defect (CSD). Green fluorescent protein (GFP)-labeled MSCs are used to evaluate patterns of cell viability and proliferation. Study Design: Prospective, controlled trial in an animal model. Methods: In 30 male rats, 8-mm calvarial CSDs were created, and divided into five groups of six animals each. In the experimental groups, the defects were injected with either chitosan gel, gel loaded with MSCs (0.3 x 106 cells/defect), gel loaded with BMP-2 (2 lg/defect), or gel loaded with both MSC and BMP-2. In the control group, the defect was left untreated. At 4 weeks, in vivo microcomputed tomography (micro-CT) analysis was performed. At 8 weeks, calvarial specimens were examined by micro-CT, histology, and immunohistochemistry. Results: New areas of bone growth were seen in the defects of all treated animals. Micro-CT analysis revealed a significant (P < .001) time-dependent increase in the regeneration of bone volume and bone area in defects treated with gel/MSC/BMP-2 as compared to all other groups. Histological analysis confirmed this difference. GFP-labeled TEB was detected within the areas of new bone, indicating cell viability and contribution to new bone growth by the injected MSC. Conclusions: This study demonstrates that an injectable form of TEB using a chitosan gel, MSC, and BMP-2 can enhance bone formation in a rat calvarial CSD.

Original languageEnglish (US)
Pages (from-to)895-901
Number of pages7
Issue number5
StatePublished - May 1 2010


  • Bone morphogenetic protein
  • Bone regeneration
  • Chitosan
  • Cranial defect
  • Mesenchymal stem cell

ASJC Scopus subject areas

  • Otorhinolaryngology

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    Stephan, S. J., Tholpady, S. S., Gross, B., Petrie-Aronin, C. E., Botchway, E. A., Nair, L. S., Ogle, R. C., & Park, S. S. (2010). Injectable tissue-engineered bone repair of a rat calvarial defect. Laryngoscope, 120(5), 895-901.