ROS scavenging nanoengineered bioactive glass interfaces reprogram macrophage immunity for tendon–bone regeneration

Abstract Failure of rotator cuff repair largely stems from ineffective regeneration of the tendon–bone interface (TBI), driven by persistent inflammation and excessive reactive oxygen species (ROS) accumulation at the biomaterial tissue interface. Here, we engineer an immunoregulatory suture interface by incorporating cerium-doped mesoporous bioactive glass nanoparticles (Ce-MBGNs) into a gelatin/tannic acid (Gel/TA) coating on polyethylene terephthalate sutures. The hierarchical Gel/TA/Ce-MBGN coating displays uniform morphology, robust adhesion and superior ROS scavenging activity. In vitro, Ce-MBGN-functionalized surfaces markedly promote osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells, while polarizing macrophages toward an anti-inflammatory M2 phenotype and substantially reducing intracellular ROS. In a rat rotator cuff repair model, high Ce-MBGN-loaded sutures significantly enhance fibrocartilaginous enthesis regeneration, increase bone mineral density and elevate M2 macrophage infiltration at the TBI. These regenerative effects correlate with suppressed HIF-1α expression in vivo, suggesting that localized redox modulation drives macrophage immunometabolic reprogramming to foster a pro-regenerative microenvironment. This Ce-MBGN-enabled interface engineering strategy simultaneously scavenges ROS, modulates immunity, and supports multi-lineage tissue regeneration at the TBI, offering a promising, clinically translatable approach for immunomodulatory suture design to improve rotator cuff repair outcomes.