Effects of Printing Shear Stress on Viability
From stem cell differentiation to cell signaling and protein expression, shear stress acts as an important biomechanical stimuli in cell biology (1-3). However, too much shear stress can lead to apoptosis or necrosis (1-3). Shear stress during bioprinting plays a large role in final viability of a construct and must be minimized. Therefore, it is necessary to identify the driving factors of shear stress, cell response to stress levels and methods to regulate and minimize these stresses.
Figure 1: General trends among nozzle (or needle) diameter, print pressure, material viscosity and shear stress. As nozzle diameter decreases and print pressure and material viscosity increase, shear stress increases.
So what affects shear stress experienced by cells, and how can it be monitored? Blaser et al. developed a fluid dynamics model to estimate shear stresses on cells with various concentrations of sodium alginate (3). This group found that needle diameter, material viscosity and print pressure all had a direct effect on shear stress. Shear stresses above 10 kPa had an adverse effect on human mescenchymal stem cell and L929 mouse fibroblast viability, while shear stresses below 5 kPa had no significant effect (3).
Minimizing shear stress can have detrimental effects on resolution, as a decrease in viscosity or increase in needle diameter leads to lower resolution. However, some methods can help to lower shear stress without affecting resolution. Shear thinning materials such as alginate decrease in viscosity as shear rate increases, minimizing shear stress during printing (4). To lower print pressure but maintain high resolution, consider using tapered needles. These needles allow for lower print pressures at the same gauge as cylindrical needles, decreasing shear stress without sacrificing resolution.
Needle diameter, print pressure and material rheological properties have an effect on more than just print speed and final resolution. The potential effect on shear stress, and thus viability, must be considered to achieve optimal results.
- Fulda, Simone et al. Cellular Stress Responses: Cell Survival and Cell Death. International Journal of Cell Biology. 2010.
- Liu J et al.Shear stress regulates endothelial cell autophagy via redox regulation and Sirt1 expression. Cell Death and Disease Nature Biotechnology. 2015 (6).
- Blaser et al. Adv Healthc Mater. 2016 Feb;5(3):326-33
- J. Malda et al., “25th Anniversary Article: Engineering Hydrogels for Biofabrication,” Advanced Materials, vol. 25, pp. 5011-5028, 2013.