In Vivo Microcomputed Tomography of Nanocrystal-Doped Tissue Engineered Scaffolds

Stacey M. Forton, Matthew T. Latourette, Maciej Parys, Matti Kiupel, Dena Shahriari, Jeff S. Sakamoto, Erik M. Shapiro

Research output: Contribution to journalArticlepeer-review

Abstract

Tissue engineered scaffolds (TES) hold promise for improving the outcome of cell-based therapeutic strategies for a variety of biomedical scenarios, including musculoskeletal injuries, soft tissue repair, and spinal cord injury. Key to TES research and development, and clinical use, is the ability to longitudinally monitor TES location, orientation, integrity, and microstructure following implantation. Here, we describe a strategy for using microcomputed tomography (microCT) to visualize TES following implantation into mice. TES were doped with highly radiopaque gadolinium oxide nanocrystals and were implanted into the hind limbs of mice. Mice underwent serial microCT over 23 weeks. TES were clearly visible over the entire time course. Alginate scaffolds underwent a 20% volume reduction over the first 6 weeks, stabilizing over the next 17 weeks. Agarose scaffold volumes were unchanged. TES attenuation was also unchanged over the entire time course, indicating a lack of nanocrystal dissolution or leakage. Histology at the implant site showed the presence of very mild inflammation, typical for a mild foreign body reaction. Blood work indicated marked elevation in liver enzymes, and hematology measured significant reduction in white blood cell counts. While extrapolation of the X-ray induced effects on hematopoiesis in these mice to humans is not straightforward, clearly this is an area for careful monitoring. Taken together, these data lend strong support that doping TES with radiopaque nanocrystals and performing microCT imaging, represents a possible strategy for enabling serial in vivo monitoring of TES.

Original languageEnglish
Pages (from-to)508-516
Number of pages9
JournalACS Biomaterials Science and Engineering
Volume2
Issue number4
Early online date29 Feb 2016
DOIs
Publication statusE-pub ahead of print - 29 Feb 2016
Externally publishedYes

Keywords

  • agarose
  • alginate
  • biomedical imaging
  • bismuth
  • gadolinium oxide
  • Hounsfield units
  • microCT
  • tissue engineered scaffold
  • X-ray

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