Nanozyme-reinforced hydrogel as a H 2 O 2 -driven oxygenerator for enhancing prosthetic interface osseointegration in rheumatoid arthritis therapy

Stem cell-based therapy has drawn attention for enhancing the osseointegration efficiency after joint replacement in the rheumatoid arthritis (RA). However, therapeutic efficacy of this approach is threatened by the accumulated reactive oxygen species (ROS) and poor oxygen supply. Herein, we develop a nanozyme-reinforced hydrogel for reshaping the hostile RA microenvironment and improving prosthetic interface osseointegration. The engineered hydrogel not only scavenges endogenously over-expressed ROS, but also synergistically produces dissolved oxygen. Such performance enables the hydrogel to be utilized as an injectable delivery vehicle of bone marrow-derived mesenchymal stem cells (BMSCs) to protect implanted cells from ROS and hypoxia-mediated death and osteogenic limitation. This nanozyme-reinforced hydrogel encapsulated with BMSCs can alleviate the symptoms of RA, including suppression of local inflammatory cytokines and improvement of osseointegration. This work provides a strategy for solving the long-lasting challenge of stem cell transplantation and revolutionizes conventional intervention methods for improving prosthetic interface osseointegration in RA.