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Resolution enhanced 3D printing of vascular structures via physical crosslink induced shrinking

Resolution enhanced 3D printing of vascular structures via physical crosslink induced shrinking

Introduction

3D bioprinting techniques such as extrusion printing, ink-jet printing and stereolithography can be used to incorporate structural complexity into engineered tissues. Consequently, achieving a high resolution with a high production throughput is of key importance. The resolution of bioprinted constructs strongly depends on an interplay of printer and ink properties. Tuning ink properties in order to enhance the resolution requires a detailed study of the mechanical properties of the ink. Furthermore, the tuning commonly results in a compromise between better resolution and other, technique-dependent drawbacks. For example, enhancing the resolution in extrusion-printing commonly requires higher viscosity inks, and thus, printing pressures. Higher printing pressures, next to possibly exceeding the printer abilities, have shown to increase shear rates in the ink during extrusion which reduces cell viability in the ink. (Murphy & Atala, 2014)             
A novel technique to increase the resolution of 3D printed constructs is to induce post-printing shrinkage. Here, a structure is printed with low resolution. Subsequent to printing, the structure is shrunken homogeneously, hence, increasing the resolution of features by reducing their size. Gong et al. (Gong et al., 2020) report the possibility of this approach via complexation induced homogenous shrinking of 3D printed anionic hydrogel constructs by infusion with cationic polymer.

Project

The aim of this project is to induce spatially controlled post-printing shrinkage via physical crosslinking. Specifically, we hypothesize that inducing the physical crosslink either locally or globally, allows for spatial shrinkage and thus resolution control.

You will start with synthesizing and characterizing an in-house polymer used to create the hydrogel. Subsequently, you explore the shrinking of the material by addition of the physical crosslink, focusing on its homogeneity and tunability. As the shrinking induces changes in the mechanical properties of the bulk gels, you will characterize those using rheology and nano indentation. After establishing the shrinking properties of bulk materials as the basis of your work, you will start exploring the shrinking of 3D printed structures as well as embedded channels and channel networks. For the channels, you will investigate additionally, how shrinking of channels influences their perfusability. Furthermore, you will investigate the influence of the shrinking on cells incorporated into your hydrogel.
Finally, we aim for you to create a channel network with enhanced resolution in a shrunken, cell laden hydrogel.

Goals

1.       Synthesis and characterization of a dually crosslinkable hydrogel
2.       Creation of bulk hydrogel constructs and in-depth investigation and tuning of
          shrinking induced resolution enhancement
3.       In-depth investigation and tuning of shrinking induced resolution enhancement  of
          a) 3D printed structures
          b) channels/channel networks in the hydrogel (created via embedded 3D printing)
4.       In-depth investigation and tuning of shrinking induced resolution enhancement of
          incorporated channels (globally and locally)
5.       Investigation of the influence of bulk hydrogel shrinking on cell fate

Gong, J., Schuurmans, C. C. L., Genderen, A. M. Van, Cao, X., Li, W., Cheng, F., … Zhang, Y. S. (2020). Complexation-induced resolution enhancement of 3D-printed hydrogel constructs. Nature Communications, 11(1), 1–14. https://doi.org/10.1038/s41467-020-14997-4

Murphy, S. V, & Atala, A. (2014). 3D bioprinting of tissues and organs. Nature Biotechnology, 32(8), 773–785. https://doi.org/10.1038/nbt.2958

Supervision
M.L. Becker MSc (Malin)
PhD Candidate
Supervision
M.R. Schot MSc (Maik)
PhD Candidate
Contact person
dr. J.C.H. Leijten (Jeroen)
Associate Professor