Hydrogel biophysical properties instruct coculture-mediated osteogenic potential

Kaitlin C. Murphy, Roberta S. Stilhano, Debika Mitra, Dejie Zhou, Samir Batarni, Eduardo Silva, Jonathan K Leach

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Cell-based approaches for bone formation require instructional cues from the surrounding environment. As an alternative to pharmacological strategies or transplanting single cell populations, one approach is to coimplant populations that can establish a new vasculature and differentiate to bone-forming osteoblasts. Mesenchymal stem/stromal cells (MSCs) possess osteogenic potential and produce numerous angiogenic growth factors. Endothelial colony-forming cells (ECFCs) are a subpopulation of endothelial progenitor cells capable of vasculogenesis in vivo and may provide endogenous cues to support MSC function. We investigated the contribution of the carrier biophysical properties to instruct entrapped human MSCs and ECFCs to simultaneously promote their osteogenic and proangiogenic potential. Compared with gels containing MSCs alone, fibrin gels engineered with increased compressive stiffness simultaneously increased the osteogenic and proangiogenic potential of entrapped cocultured cells. ECFCs produced bone morphogenetic protein-2 (BMP-2), a potent osteoinductive molecule, and increases in BMP-2 secretion correlated with gel stiffness. Coculture of MSCs with ECFCs transduced to knockdown BMP-2 production abrogated the osteogenic response to levels observed with MSCs alone. These results demonstrate that physical properties of engineered hydrogels modulate the function of cocultured cells in the absence of inductive cues, thus increasing the translational potential of coimplantation to speed bone formation and repair.

Original languageEnglish (US)
Pages (from-to)477-486
Number of pages10
JournalFASEB Journal
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • BMP-2
  • ECFC
  • Fibrin
  • Mesenchymal stem cell
  • Osteogenesis

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Murphy, K. C., Stilhano, R. S., Mitra, D., Zhou, D., Batarni, S., Silva, E., & Leach, J. K. (2016). Hydrogel biophysical properties instruct coculture-mediated osteogenic potential. FASEB Journal, 30(1), 477-486. https://doi.org/10.1096/fj.15-279984