Cell Protection Against Mechanical Stress Through Silk Ionomer Electrostatic Layer-By-Layer Deposition

Applications such as systemic transplantation, tissue engineering, and stem cell-based therapies are promising solutions for treating diseases and supporting organ functions. These approaches involve ex vivo cell manipulation, exposing them to mechanical stresses such as shear, impairing the plasma membranes of cells, reducing cell viability and hindering therapeutic outcomes. Cell encapsulation has shown promise in mitigating these effects by enhancing their resistance to mechanical damage by providing cytocompatible coatings around the cells. We have previously successfully encapsulated THP-1 immune cells through LbL electrostatic deposition of silk ionomers. Here, we continue to explore the cell functionality, protection under shear stress, and the tunability of the layer thickness post-encapsulation. The coating thickness was measured using QCM-D and AFM to assess the coated cells' stiffness. The robustness of the coating was studied by applying sheer stress by extruding cells through needles in 6% PEG solution and we assessed the ability of the encapsulated THP-1 cells to differentiate into macrophage phenotypes, monitoring their response to differentiation stimuli. The results show that silk encapsulation effectively shields cells from shear stress, preserves their functionality, and protects them against macromolecules. This study advances the application of silk-based cell encapsulation for enhanced protection in therapeutic cell delivery and regenerative medicine.