A facile method to fabricate cell-laden hydrogel microparticles of tunable sizes using thermal inkjet bioprinting

Abstract

This study investigates the application of a drop-on-demand (DOD) thermal inkjet (TIJ)-based bioprinting system for the fabrication of cell-laden hydrogel microparticles (HMPs) with tunable sizes. The TIJ bioprinting technique involves the formation of vapor bubbles within the print chamber through thermal energy, expelling small droplets of bio-ink onto a substrate. The study employs a heat-treated saponified gelatin-based bio-ink, HSP-GelMA. This bio-ink is modified through methacrylic anhydride functionalization and undergoes subsequent saponification and heat treatment processes. Various concentrations of SPAN 80 surfactant in mineral oil were evaluated to assess their influence on HMP size and stability. The results indicate a direct correlation, with higher SPAN 80 concentrations resulting in smaller and more stable HMPs. The study further investigates the influence of jetting volume on HMP size distribution, revealing that larger jetting volumes lead to increased HMP sizes, attributed to droplet coalescence. This is supported by our further study via a Monte Carlo simulation, which shows that the mean droplet diameter grows approximately linear with the number of dispensed droplets. In addition, the study demonstrates the capability of the TIJ bioprinting system to achieve multimaterial encapsulation within HMPs, exemplified by staining living cells with distinct cytoplasmic membrane dyes. The presented approach provides insights into the controlled fabrication of cell-laden HMPs, highlighting the versatility of the TIJ bioprinting system for potential applications in tissue engineering and drug delivery.