Energetics and Kinetics of Membrane Permeation of Photoresists for Bioprinting

Abstract 3D bioprinting is a promising technology which typically uses bioinks to pattern cells and their scaffolds. The selection of cytocompatible inks is critical for the printing success. In laser‐based 3D bioprinting, photoresist molecules are used as bioinks. However, the interaction of photoresists with lipid membranes and their permeation into the cell remains poorly understood. Here, molecular dynamics simulations and in vitro assays address this issue, retrieving partition coefficients, free energies, and permeabilities for twelve commonly used photoresists in model lipid bilayers. Crossing the hydrophobic center of the membrane constitutes the rate limiting step during permeation. In addition, three photoresists feature a preferential localization site at the acyl chain head group interface. Photoresist permeabilities range over ten orders of magnitude, with some molecules being membrane‐permeable on bioprinting timescales. Moreover, permeation correlates well with the oil–water partition coefficients and is severely hampered by the lipid ordering imposed by the lipid saturation. Overall, the mechanism of interaction of photoresists with model lipid bilayers is provided here, helping to classify them according to their residence in the membrane and permeation through it. This is useful information which will help guide the selection of cytocompatible photoresists for 3D bioprinting.