Catalytic MXene implant interfaces reprogram radiation-induced foreign body response to prevent capsular contracture.

Radiotherapy markedly exacerbates foreign body response (FBR) to silicone implants, driving capsular fibrosis and contracture, yet actionable interfacial mechanisms remain insufficiently defined. Here, we engineer an implant-centered Ti3C2Tx MXene-modified PDMS coating (APM) to modulate the redox microenvironment at the tissue-implant interface to reprogram radiotherapy-induced FBR. Oxygen plasma activation and 3-aminopropyltriethoxysilane (APTES) silanization enable covalent anchoring of single-layer MXene nanosheets onto PDMS, yielding a conformal APM film with enhanced hydrophilicity, preserved layered MXene architecture, enzyme-mimicking ROS-scavenging activity, and excellent cytocompatibility. Transcriptomic profiling guides the study, revealing the coordinated downregulation of inflammatory and extracellular matrix remodeling pathways. Mechanistically, interfacial redox regulation dampens NF-κB signaling and reduces endothelial ICAM-1 expression, thereby limiting monocyte adhesion and downstream inflammatory amplification. A tri-culture endothelial-macrophage-fibroblast model further demonstrates that MXene interfaces disrupt pro-inflammatory crosstalk and inhibit myofibroblast activation. In a murine peri-implant irradiation model, APM-coated implants preserve a CD31+/ICAM-1-low microvasculature, reduce peri-implant pro-inflammatory macrophage accumulation, and significantly decrease capsular thickness and collagen deposition. Collectively, these findings demonstrate that MXene-based catalytic coatings can disrupt the positive feedback loop between radiation injury and fibrotic capsule formation, offering a mechanistically grounded strategy to mitigate implant-associated fibrosis.