A Magnetically Responsive Selenium-Doped CeO₂ Nanozyme for On-Demand Reactive Oxygen Species Modulation and Enhanced Tissue Regeneration.

Abstract

Precise control of reactive oxygen species (ROS) is indispensable during tissue repairing. Inorganic nanozymes such as cerium dioxide (CeO₂) have emerged as potent ROS modulators, however, their fixed catalytic activity prevents on-demand adaptation to the rapidly changing immune microenvironment. Here, we reported a magnetically responsive dynamic antioxidant system that autonomously tunes its ROS-scavenging capacity on demand. Selenium (Se) doping was first exploited to engineer high-density oxygen vacancies (Vo) in the CeO₂ lattice, enabling the nanozyme intrinsic antioxidant activity enhancement. Its catalytic efficiency could be further amplified under a static magnetic field (SMF). In vitro analysis revealed that Se-CeO₂ under SMF significantly promoted the polarization of macrophages toward the pro-regenerative M2 phenotype. The as-prepared Se-CeO₂ was subsequently loaded into a sodium alginate-hyaluronic acid hydrogel (SCSH-Gel), witnessed to protect chondrocytes and fibroblasts from oxidative stress in vitro. Followed in vivo tests found SMF and Se-CeO₂ synergistically accelerate neocartilage formation in a cartilage defect model and promoted re-epithelialization in a full-thickness skin-wound model. Collectively, our results demonstrated that Se doping coupled with magnetic actuation enables inorganic nanozymes to dynamically modulate ROS homeostasis, offering a versatile strategy for precisely programming the microenvironment to facilitate tissue regeneration.