Multimodal Label-Free Imaging for Detecting Maturation of Engineered Osteogenic Grafts

Jenna N. Harvestine, Clay S. Sheaff, Cai Li, Anne K. Haudenschild, Marissa A. Gionet-Gonzales, Jerry C. Hu, Kyriacos A Athanasiou, Laura Marcu, J. Kent Leach

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


There is a critical need to develop noninvasive, nondestructive methods for assessing the quality of engineered constructs prior to implantation. Currently, the composition and maturity of engineered tissues are assessed using destructive, costly, and time-consuming biochemical and mechanical analyses. The goal of this study was to use noninvasive, multimodal imaging to monitor osteogenic differentiation and matrix deposition by human mesenchymal stem/stromal cells (MSCs) during in vitro culture. MSCs were encapsulated in alginate hydrogels and cultured in osteogenic conditions for 4 weeks. Samples were evaluated using fluorescence lifetime imaging (FLIm) and ultrasound backscatter microscopy (UBM) prior to traditional biochemical and mechanical testing. Using linear regression analysis, we identified strong correlations between imaging parameters (e.g., fluorescence lifetime and acoustic attenuation coefficient) and destructive mechanical and biochemical tests to assess the maturation of osteogenically induced constructs. These data demonstrate the promise of nondestructive label-free imaging techniques to noninvasively ascertain the progression and maturity of tissue engineered bone grafts.

Original languageEnglish (US)
Pages (from-to)1956-1966
Number of pages11
JournalACS Biomaterials Science and Engineering
Issue number4
StatePublished - Apr 8 2019


  • fluorescence lifetime imaging
  • mesenchymal stem/stromal cell
  • osteogenic differentiation
  • osteogenic graft
  • ultrasound backscatter

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering


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