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

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.