Master Assignments

Self-healing Bio-ink for 3D Tissue Printing

ASSIGNMENT STARTS ON 1 jULY

Self-healing Bio-ink for 3D Tissue Printing

AIM

Engineer a self-healing bio-ink based on microgels for 3D tissue printing.

INTRODUCTION

Hydrogel microbeads (i.e., microgels) can be used for the bottom-up fabrication of engineered tissue constructs. Microgel-based tissue constructs offer several advantages over conventional solid bulk tissue constructs. For example, they contain interconnected interstitial spaces that facilitate diffusion of nutrients and ingrowth of neuronal and vascular networks.[1] Endowing the microgels with self-adhesive properties enables the fabrication of shape-stable injectable bio-inks with self-assembling and self-healing properties.[2]

Recently, our group has developed a microfluidic platform for the production of biotin-functionalized microgels.[3] These microgels can be straightforwardly transformed into self-adhesive microgels by forming macromolecular interactions using avidin type molecules.[4] We hypothesize that the self-annealing properties of biotin-functionalized microgels can also be used to produce a bio-ink for the 3D printing of engineered tissues. Such a microgel-based bio-ink can then be leveraged for the facile and rapid fabrication of porous engineered tissues.

In this project, the student will develop a self-healing bio-ink based on annealable microgels. The bio-ink will be produced using advanced droplet microfluidics, characterized using rheology, and optimized for the 3D printing of porous 3D tissue constructs.

GOALS

  1. Produce cell-sized microgels using microfluidic droplet generators
  2. Functionalize microgels with biotins and use avidin-type molecules to generate a self-healing ink
  3. Characterize the rheological properties of the ink
  4. Mix the ink with cells and setup a bioprinting assay
  5. 3D print an engineered tissue construct

TECHNIQUES

The student will learn several state-of-the art techniques, including droplet microfluidics, various hydrogel crosslinking, rheological analysis, (3D) (stem) cell culture, immunohistochemistry, and confocal fluorescence imaging and apply this skill set in a top-level institute to perform pioneering work on self-healing inks for 3D (bio)printing.

REFERENCES

1.   Matsunaga, Y.T., Y. Morimoto, and S. Takeuchi, Molding cell beads for rapid
      construction of macroscopic 3D tissue architecture. Advanced Materials, 2011.
      23(12): p. H90-4.
2.   Griffin, D.R., et al., Accelerated wound healing by injectable microporous gel
      scaffolds assembled from annealed building blocks. Nat Mater, 2015. 14(7):
      p. 737-44.
3.   Kamperman, T., Microgel Technology to Advance Modular Tissue Engineering, in
      Developmental BioEngineering. 2018, University of Twente. p. 174.
4.   Nyström, L., et al., Avidin-biotin cross-linked microgel multilayers as carriers for
      antimicrobial peptides. Biomacromolecules, 2018.

Supervision
Tom Kamperman PhD
Supervision
dr. J.C.H. Leijten (Jeroen)
Assistant Professor
Contact person
dr. J.C. Alers (Janneke)
Lecturer