Rapid healing of femoral defects in rats with low dose sustained BMP2 expression from PEGDA hydrogel microspheres

Corinne Sonnet, C. Lashan Simpson, Ronke M. Olabisi, Kayleigh Sullivan, Zawaunyka Lazard, Zbigniew Gugala, John F. Peroni, J. Michael Weh, Alan R. Davis, Jennifer L. West, Elizabeth A. Olmsted-Davis

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Current strategies for bone regeneration after traumatic injury often fail to provide adequate healing and integration. Here, we combined the poly (ethylene glycol) diacrylate (PEGDA) hydrogel with allogeneic "carrier" cells transduced with an adenovirus expressing BMP2. The system is unique in that the biomaterial encapsulates the cells, shielding them and thus suppressing destructive inflammatory processes. Using this system, complete healing of a 5 mm-long femur defect in a rat model occurs in under 3 weeks, through secretion of 100-fold lower levels of protein as compared to doses of recombinant BMP2 protein used in studies which lead to healing in 2-3 months. New bone formation was evaluated radiographically, histologically, and biomechanically at 2, 3, 6, 9, and 12 weeks after surgery. Rapid bone formation bridged the defect area and reliably integrated into the adjacent skeletal bone as early as 2 weeks. At 3 weeks, biomechanical analysis showed the new bone to possess 79% of torsional strength of the intact contralateral femur. Histological evaluation showed normal bone healing, with no infiltration of inflammatory cells with the bone being stable approximately 1 year later. We propose that these osteoinductive microspheres offer a more efficacious and safer clinical option over the use of rhBMP2.

Original languageEnglish (US)
Pages (from-to)1597-1604
Number of pages8
JournalJournal of Orthopaedic Research
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2013

Keywords

  • BMP2
  • PEGDA
  • bone healing
  • critical size defect
  • microencapsulation

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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    Sonnet, C., Simpson, C. L., Olabisi, R. M., Sullivan, K., Lazard, Z., Gugala, Z., Peroni, J. F., Weh, J. M., Davis, A. R., West, J. L., & Olmsted-Davis, E. A. (2013). Rapid healing of femoral defects in rats with low dose sustained BMP2 expression from PEGDA hydrogel microspheres. Journal of Orthopaedic Research, 31(10), 1597-1604. https://doi.org/10.1002/jor.22407