Temporary silk nanocoatings preserve immune cell functions and protection against biochemical and mechanical stressors.

Cell-based therapies offer transformative potential for treating a range of diseases, however, maintaining desirable cell functions under environmental and biochemical stresses remains a major challenge. In the present study, silk ionomer nanoencapsulation using layer-by-layer (LbL) deposition was utilized as a versatile strategy to provide temporary cell protection from these stresses and preserve cell functions for downstream use. Using THP-1 immune cells, tunable encapsulation of the cells with up to 10 bilayers of silk was demonstrated. Characterization by quartz crystal microbalance (QCM-D) and atomic force microscopy (AFM) revealed nonlinear thickness growth (∼800 nm) and peak stiffness of 231 kPa above five bilayers, indicating a transition from rigid initial layer deposition, to softer outer layers. We demonstrate that the silk ionomer coatings preserved cellular functions, including differentiation into M1 and M2 macrophages, the associated cytokine profiles (TNF-α, IL-1β, IL-10, TGF-β), and expression of cell surface markers (CD68, CD206) when compared to the uncoated controls. Notably, these temporary coatings blocked antibody binding to CD14/CD68 receptors and also protected cells from shear stress during extrusion through a 34G needle at 200 μL/min, resulting in greater than a 70 % increase in cell survival compared to the uncoated cells during extrusion. These results establish silk ionomers as a robust biomaterials platform for enhancing the mechanical resilience and immune evasion of cells in advanced applications, such as for 3D bioprinting, adoptive immunotherapy, and regenerative transplantation.