Cerium Nanozyme-Powered Hydrogel Microspheres Alleviate Thromboangiitis Obliterans via Enhanced Stem Cell Therapy

Thromboangiitis obliterans (TAO) is a chronic peripheral vascular condition characterized by thrombotic and inflammatory acceleration. As a promising therapeutic modality for the TAO, mesenchymal stem cells (MSCs) transplantation is expected to circumvent the traditional drug therapy and surgical interventions. Nonetheless, the MSCs therapy is hindered owing to poor survival, retention, and engraftment of the transplanted cells. The objective of this research is to develop MSCs- and cerium oxide nanoparticles (CeNPs)-laden injectable methacrylated gelatin (GelMA)-based hydrogel microspheres by using microfluidics and discern their potential to regulate oxidative stress and inflammation in a rat model of TAO. The CeNPs-loaded photocroslinkable GelMA microspheres not only protected the transplanted MSCs against oxidative stress but also facilitated endothelial functional recovery, revascularization of the ischemic limb, and suppression of the inflammatory factors from the macrophages. The hydrogel microspheres further conferred mechanical support and prolonged the residence time of transplanted MSCs to enhance the efficacy of cell therapy. In vivo study confirmed that the combination of MSCs and CeNPs in the microsphere exhibited a positive synergistic effect on tissue recovery and angiogenesis. Taken together, this work presents a novel therapeutic approach based on the integration of stem cells and nano-micron combined hydrogel microspheres, which may have implications for TAO therapy.