Influence of viscosity and velocity of administration on the performance of hyaluronic acid as a vehicle for bioprinting and injectable cell therapy: a computer simulation approach and in vitro validation

Background: Hyaluronic acid (HA) is a natural polymer widely used as a vehicle in injectable cell therapy for the treatment of arthropathies. Objective: To estimate, through computational simulations and in vitro validation, the influence of HA’s physicochemical properties and administration speed on the shear stress generated in the syringe/needle system, as well as the associated risk to cell viability during administration. Methods: The influence of viscosity was evaluated by considering the rheological parameters corresponding to HA concentrations of 6, 8, 10, 12, and 15 mg/mL. For assessing the impact of administration speed, values representative of the typical speed range used in clinical procedures were considered. Simulations were used to estimate shear stress as a function of administration speed for each viscosity level. Results: The findings revealed a directly proportional relationship between viscosity and administration speed with the magnitude of shear stress. Notably, the highest viscosity formulation, when administered at the fastest speed, reached "critical values" of shear stress associated with mechanical damage to cell membranes and cell death. Conversely, lower viscosity HA exhibited reduced stress levels, indicating it as the potentially preferred formulation for injectable cell therapy. The in vitro cell culture assays corroborated the computational simulation results. Conclusions: The administration of HA demonstrates a viscosity- and speed-dependent effect on shear stress, which should be carefully considered for its application in bioprinting and injectable cell therapies.