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Synthetic Cell-Based Tissues for Bottom-Up Assembly of Artificial Lymphatic Organs.

Anna Burgstaller1,2,3, Tamara Nink1, Niklas Walter1

  • 1INM - Leibniz Institute for New Materials, Campus D2 2, 66123, Saarbrücken, Germany.

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Summary

Engineered synthetic cells self-assemble into 3D lymphatic tissues (lymphBUTs). These living tissue hybrids integrate human immune cells, driving T cell activation and enabling therapeutic applications.

Keywords:
bottom‐up synthetic biologyimmuno‐biophysicsregulatory T cellssynthetic cellstissue engineering

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Area of Science:

  • Biomimetic engineering
  • Synthetic biology
  • Tissue engineering

Background:

  • Synthetic cells offer a biomimetic platform for studying cellular functions and therapeutics.
  • Programming synthetic cells into 3D collectives for tissue replication is an underexplored area.

Purpose of the Study:

  • To engineer synthetic cells capable of self-assembly into 3D tissues.
  • To investigate the integration and function of immune cells within these synthetic tissues.
  • To explore therapeutic applications of engineered 3D synthetic tissues.

Main Methods:

  • Engineered self-assembly properties into synthetic cells.
  • Fabricated millimeter-sized 3D lymphatic bottom-up tissues (lymphBUTs).
  • Assessed mechanical adaptability, metabolic activity, and microstructural organization of lymphBUTs.
  • Investigated infiltration and functional integration of primary human immune cells.
  • Evaluated T cell activation and ex vivo expansion of regulatory CD8+ T cells.

Main Results:

  • Successfully formed millimeter-sized lymphBUTs with adaptable mechanics and hierarchical structure.
  • Demonstrated spontaneous infiltration and functional integration of human immune cells into lymphBUTs, forming living tissue hybrids.
  • Showcased that 3D organization and mechanical support within lymphBUTs enhance T cell activation.
  • Validated lymphBUTs for ex vivo expansion of regulatory CD8+ T cells.

Conclusions:

  • Synthetic cells can be engineered into self-organizing 3D tissues.
  • Engineered lymphBUTs facilitate functional integration of living immune cells, creating advanced tissue hybrids.
  • This approach advances synthetic cell engineering towards functional 3D tissue structures with therapeutic potential.