Excessive Shear Rate, Not Shear Stress, Influences Cell Mechanical Damage in Small-Bore Needle Injections

Cell therapies and 3D bioprinting often require suspended cells to be delivered through needles of 20-gauge and smaller. This often damages cells, affecting their short and long-term viability. Most researchers have attributed this to excessive viscous stresses encountered entering or within the needle, but the experimental evidence contradicts that, as higher viscosity suspension fluids generally yield higher cell viabilities when injected at the same flow rate. We therefore sought to determine the most relevant fluid flow parameter influencing cell mechanical damage. A combination of reprocessing published results and cell injection experiments were conducted. Human umbilical vein endothelial cells (HUVECs) were suspended in Newtonian fluids of varying viscosities and injected through 30-gauge syringe needles in experiments that controlled for either shear stress or shear rate (a kinematic quantity expressing relative velocity of adjacent fluid layers). Based on evidence from injection experiments using a variety of fluids, it is shown that increasing shear rate better explains reductions in cell viability than increasing shear stress. Knowledge that shear rate is a more relevant fluid mechanical parameter governing mechanical damage provides a rational basis for designing injection protocols (injectors and suspension fluid rheological properties) to maximize cell viability.