A Versatile Immune Protective Armor to Enhance the Regenerative Potential of Exogenous Stem Cells

Host immune rejection has long been recognized as a major contributor to the poor survival rates of exogenous stem cells (ESCs). In this study, we present a simple and versatile strategy to protect ESCs from host immune system insults by developing a protective "armor." This armor was designed using tannic acid (TA), leveraging its strong affinity for biomacromolecules and its anti-inflammatory properties. Prior to implantation, the armor can be readily applied to the surface of individual ESCs, cell aggregates, cell sheets, or cell-laden hydrogel systems by simply immersing them in a TA solution for several seconds, without additional processing steps. The TA-based armor effectively modulates the acute inflammatory response during the initial days postimplantation by scavenging reactive oxygen species (ROS), thereby creating an ESCs-friendly immune microenvironment. This was evidenced by reduction in the infiltration of pro-inflammatory immune cells and the secretion of pro-inflammatory cytokines. Consequently, the survival of engrafted ESCs was significantly enhanced, with preserved stemness and immunomodulatory functions. The regenerative potential of ESCs was further demonstrated in a rat periodontal defect model. These findings provide a novel approach for enhancing the regenerative performance of ESCs and offer a straightforward and versatile strategy to shield ESCs from host immune rejection.