Silk Ionomer-Based Modular Nanocoatings for Potential Immuno-Regenerative Cell Therapy in Osteoarthritis

Silk protein ionomer-based layer-by-layer (LBL) nanocoating strategy was utilized to preserve the viability, metabolic activity and differentiation potential of human mesenchymal stem cells (hMSCs) in an in vitro inflamed osteoarthritis (OA) tissue niche. These temporary ionomer coatings for cell protection were functionalized with cytokines to impart immune-modulatory behavior. The cytokine-functionalized ionomer nanocoatings polarized neutral M0 macrophages into M1 and M2 subtypes, depending on the specific cytokine used, thereby reducing synovial inflammation in an in vitro setup. This approach would potentially abrogate the need for ex vivo polarization before transplantation during immunotherapy. The modular nature of these silk ionomer nanocoatings in tailoring cell surface stability was further validated by extending the cell coatings to 3D spheroids and also by introducing tyramine to the cationic silk ionomer to facilitate covalent crosslinking in addition to the electrostatic interactions between the cell surface and the ionomers. These results demonstrate the versatile and modular nature of silk-based ionomer cell nanocoatings, allowing control at material, cellular, and spheroid levels to tune coating stability and inflammatory responses. These systems uniquely impart immunomodulatory function, providing a biomaterial platform for cell-based immune-regenerative therapy, such as for OA and other inflammatory diseases.