Disease modeling increasingly relies on microfluidic systems, miniaturized cell culture platforms that mimic in vivo conditions. Stereolithography (SLA) three-dimensional (3D) printing represents an attractive method to create highly detailed, complex 3D objects from liquid photopolymer resins. However, numerous resins have been reported as cytotoxic, and their use for chip printing intended to support sensitive cell types for extended periods of time is therefore discouraged. In this study, two commercially available clear resins and a combination of post-printing treatments, including UV-light exposure or heat treatment with or without a parylene-C coating, were tested. Both resins released cytotoxic monomers when uncoated by a parylene-C layer, regardless of the post-treatment. By contrast, parylene-C coating not only reduced monomer leaching but also prevented absorption of small molecules by the material. The viability of motor neuron precursor cells cultured in the SLA 3D printed chips was significantly reduced in the absence of parylene-C. Furthermore, as physiological function is essential in such systems, motor neuron precursor cells were differentiated into motor neuron spheroids and their neurite outgrowth was assessed over three days while maintained in the chips. This further confirmed the effectiveness of the parylene-C coating. Cellular testing identified the UV-light exposed, parylene-C coated Formlabs Clear V4 resin condition as the most suitable for motor neuron culture, demonstrating that this condition was able to support a sensitive cell type relevant for applications in numerous disease modeling systems. Altogether, these results demonstrate that 3D-printed microfluidic chips require appropriate post-processing to ensure biocompatibility. • SLA 3D printing is an economical and accessible alternative to PDMS devices. • Resins are cytotoxic, limiting their use when applied to cell culture. • Overcuring and a thin parylene-C coating abrogates resin cytotoxicity. • Resulting chips are suitable for culturing sensitive hiPSC-derived neurons.
Scherrer et al. (Sun,) studied this question.