ASSIGNMENT STARTS ON 1 JULY
DOCKING to Serve and Protect
AIM
To endow individual cells with protective hydrogel nanocoatings using direct on-cell crosslinking (DOCKING).
INTRODUCTION
3D engineered tissue constructs can be produced using a variety of biofabrication processes. Typically, a cell-laden bio-ink is injected, sprayed, or printed to form a larger shape stable 3D construct. Ideally, these additive manufacturing processes are performed using relatively small nozzles at high flow rates to enable a rapid fabrication process while maintaining high resolution. However, the rapid transfer of viscous bio-inks through small nozzles results in high shear stress on the cells membrane, which results in cell death. Furthermore, the impact of ejected cells upon deposition also exerts an additional harmful force on the cellular membrane due to significant cell deformations.
This project aims to protect cells from mechanically induced damage during biofabrication, by providing the cells with a stable cellular nanocoating’. Specifically, it aims to directly crosslink a polymer network onto the cellular membrane using a cytocompatible enzymatic crosslinking reaction (i.e., DOCKING). It is hypothesized, that the resulting polymer nanocoating can stabilize the cellular membrane and mechanically support the cells during spraying or 3D printing. Moreover, modification of the polymer nanocoatings with bioactive moieties could potentially serve as a cell stimulating microenvironment. If successful, DOCKING represents a facile, novel, and widely applicable method to serve and protect cells in biofabricated tissue engineering constructs.
GOALS
- Engineer cellular nanocoatings using DOCKING
- Characterize the coated cells using fluorescent confocal microscopy
- Assess the viability of nanocoated cells vs bare cells after various biofabrication processes
- Demonstrate the DOCKING of bioactive polymer nanocoatings
TECHNIQUES
This interdisciplinary assignment focuses on material engineering, biology, and chemistry. Core technologies include: enzymatic crosslinking, fluorescence confocal microscopy, cell culture, biofabrication (i.e., injection molding, and/or spraying, and/or 3D printing).
SUGGESTED LITERATURE
- Shear stress-induced cell damage [1]
- Hydrogels for biofabrication: the interplay between viscosity, shape fidelity, and cytocompatibility [2]
- Cell survival upon impact after spraying [3]
- Direct on-cell crosslinking (DOCKING) method [4]
1. Blaeser, A., et al., Controlling Shear Stress in 3D Bioprinting is a Key Factor to Balance
Printing Resolution and Stem Cell Integrity. Adv Healthc Mater, 2016. 5(3): p. 326-33.
2. Malda, J., et al., 25th anniversary article: Engineering hydrogels for biofabrication.
Advanced Materials, 2013. 25(36): p. 5011-28.
3. Hendriks, J., et al., Optimizing cell viability in droplet-based cell deposition.
Sci Rep, 2015. 5: p. 11304.
4. Kamperman, T., Microgel Technology to Advance Modular Tissue Engineering, in
Developmental BioEngineering. 2018, University of Twente. p. 174.
SUPERVISION