Monitoring nutrient transport in tissue-engineered grafts

Jun Liu, Janneke Hilderink, Tom A. M. Groothuis, Cees Otto, Clemens A. van Blitterswijk, Jan de Boer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Limited nutrient diffusion in three-dimensional (3D) constructs is a major concern in tissue engineering. Therefore, monitoring nutrient availability and diffusion within a scaffold is an important asset. Since nutrients come in various forms, we have investigated the diffusion of the oxygen, luciferin and dextran molecules within tissue-engineered constructs using optical imaging technologies. First, oxygen availability and diffusion were investigated, using transgenic cell lines in which a hypoxia-responsive element drives expression of the green fluorescent protein gene. Using confocal imaging, we observed oxygen limitation, starting at around 200 ?m from the periphery in the context of agarose gel with 1 million CHO cells. Diffusion of luciferin was monitored real-time in agarose gels using a cell line in which the luciferase gene was driven by a constitutively active CMV promoter. Gel concentration affected the diffusion rate of luciferin. Furthermore, we assessed the diffusion rates of fluorescent dextran molecules of different molecular weights in biomaterials by fluorescence recovery after photobleaching (FRAP) and observed that diffusion depended on both molecular size and gel concentration. In conclusion, we have validated a set of efficient tools to investigate molecular diffusion of a range of molecules and to optimize biomaterials design in order to improve nutrient delivery.
Original languageEnglish
Pages (from-to)952-960
JournalJournal of Tissue Engineering and Regenerative Medicine
Issue number8
Publication statusPublished - Aug 2015


  • tissue engineering
  • nutrient supply
  • 3D scaffold
  • bioluminescent imaging
  • FRAP
  • hypoxia


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