Tumor bioengineering using a transglutaminase crosslinked hydrogel

PLoS One. 2014 Aug 18;9(8):e105616. doi: 10.1371/journal.pone.0105616. eCollection 2014.


Development of a physiologically relevant 3D model system for cancer research and drug development is a current challenge. We have adopted a 3D culture system based on a transglutaminase-crosslinked gelatin gel (Col-Tgel) to mimic the tumor 3D microenvironment. The system has several unique advantages over other alternatives including presenting cell-matrix interaction sites from collagen-derived peptides, geometry-initiated multicellular tumor spheroids, and metabolic gradients in the tumor microenvironment. Also it provides a controllable wide spectrum of gel stiffness for mechanical signals, and technical compatibility with imaging based screening due to its transparent properties. In addition, the Col-Tgel provides a cure-in-situ delivery vehicle for tumor xenograft formation in animals enhancing tumor cell uptake rate. Overall, this distinctive 3D system could offer a platform to more accurately mimic in vivo situations to study tumor formation and progression both in vitro and in vivo.

MeSH terms

  • Animals
  • Cell Culture Techniques / methods*
  • Cell Line, Tumor
  • Coculture Techniques / methods
  • Collagen / metabolism*
  • Drug Screening Assays, Antitumor / methods
  • Humans
  • Hydrogels / metabolism*
  • Mice, Nude
  • Neoplasms / enzymology*
  • Neoplasms / metabolism
  • Spheroids, Cellular
  • Transglutaminases / metabolism*
  • Tumor Cells, Cultured
  • Tumor Microenvironment*


  • Hydrogels
  • Collagen
  • Transglutaminases

Grant support

The authors have no support or funding to report.