DeLIMIT Project

DeLIMIT Project

3D Bioprinting Techniques for Building Tissue Constructs that Mimic the Tumor Microenvironment (DeLIMIT) – 100PED/03.01.2017 

Duration: 03 January 2017 – 30 June 2018

Coordinator: Clinical County Emergency Hospital „Pius Brînzeu” Timișoara – OncoGen Center for Cellular and Gene Therapies

Partners: „Victor Babeș” University of Medicine and Pharmacy Timișoara

Specific objective in the first phase of DeLIMIT project was generation of tumor spheroids from breast and colon tumor cells, 3D bioprinting of multicellular spheroids and in vitro characterization of tumor models. In the second phase of the project we aimed to validate in vivo the optimal tumor model obtained by 3D bioprinting, referring to in vivo development of tumor models, as well as computational simulation / modelling of cellular rearrangements after 3D bioprinting.  

More details: www.3dbioprinting-oncogen.com

Results:

  • Validated the 3D bioprinting methodology of tumor models in vitro, using 3 distinct cellular types, originating from peri-tumoral microenvironment (tumor-associated fibroblasts – TAF and T lymphocytes) and tumor cells;
  • Validated 2 distinct tumor models in vitro: triple-layered model and torsional model;
  • Validated in vivo the triple-layered 3D bioprinted tumor model in CD1 Nu/Nu immunosuppressed mice; validation of tumor development was performed in vivo using the Hamamatsu Aequoria Imaging System (quantification of tumor development), followed by in vitro validation of tumor model on tissue slides, showing cellular distribution and characteristic markers expression.
  • Validated computational simulation model of tumor development.
Fig. 1. HT-29 colon cancer tumor spheroids visualized by stereomicroscopy (scale bar – 200 µm).
Fig. 2. Digital models of developed tissue structures: toroidal model (A) and triple-layered model (B-D).
Fig. 3. Computational models of tissue structures generated at scale 1:1, visualized with (A, C) and without the dispersant hydrogel (B,D).
Fig. 4. Hematoxylin and eosin staining of tumor models bioprinted after 6 days of growth in vitro.
Fig. 5. Triple-layered tumor model grown in vivo.
Fig. 6. Optimization experiment of printing process with two different types of hydrogel.

Participation in scientific events:

  1. Neagu A, Bojin F, Bejenariu MI, Neagu M, Cristea A, Popescu R, Păunescu V. 3D bioprinting techniques for building model tissues” – oral presentation, the 29th National Conference of the Romanian Society of Physiology, 25-27 May 2017, Timişoara.
  2. Bojin F, Neagu A, Bejenariu MI, Cean A, Popescu R, Neagu M, Cristea A, Păunescu V. “3D bioprinting techniques for building model tissues that mimic the tumor microenvironment” – oral presentation, BIOFABRICATION 2017 International Conference on Biofabrication, 15-18 October 2017, Beijing, China.
  3. Bojin F, Bejenariu MI, Robu A, Cean A, Popescu R, Neagu M, Gavriliuc O, Neagu A, Păunescu V. “Bioprinted models of the tumor microenvironment: in vivo evaluation and computer simulations” – oral presentation, BIOFABRICATION 2018 International Conference on Biofabrication, 28-31 October 2018, Würzburg, Germany.
  4. Neagu A, Brakke K, Robu A, Bejenariu MI, Koudan E, Bulanova E, Parfenov V, Hesuani Y, Kharin A, Timoshenko V, Mironov V, “Sacrificial multicellular spheroids (sacrospheres) for the biofabrication of tubular tissue constructs”, poster, BIOFABRICATION 2017 International Conference on Biofabrication, 15-18 October 2017, Beijing, China.

Research articles:

  1. Neagu A. (2017) Role of computer simulation to predict the outcome of 3D bioprinting. Journal of 3D Printing in Medicine 1(2):103-121.
  2. Robu A, Robu N, Neagu A. (2018) New software tools for hydrogel-based bioprinting. Proceedings of SACI 2018, IEEE 12th International Symposium on Applied Computational Intelligence and Informatics, May 17-19, 2018, Timisoara, Romania. DOI: 10.1109/SACI.2018.8440971.

Contact

Pius Branzeu Clinical Emergency Hospital
300723 Timisoara, Romania
156, Liviu Rebreanu Boulevard
info@oncogen.ro

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