Ti3C2Tx MXene‐Decorated 3D‐Printed Ceramic Scaffolds for Enhancing Osteogenesis by Spatiotemporally Orchestrating Inflammatory and Bone Repair Responses

Abstract

AbstractInflammatory responses play a central role in coordinating biomaterial‐mediated tissue regeneration. However, precise modulation of dynamic variations in microenvironmental inflammation post‐implantation remains challenging. In this study, the traditional β‐tricalcium phosphate‐based scaffold is remodeled via ultrathin MXene‐Ti3C2 decoration and Zn2+/Sr2+ ion‐substitution, endowing the scaffold with excellent reactive oxygen species‐scavenging ability, near‐infrared responsivity, and enhanced mechanical properties. The induction of mild hyperthermia around the implant via periodic near‐infrared irradiation facilitates spatiotemporal regulation of inflammatory cytokines secreted by a spectrum of macrophage phenotypes. The process initially amplifies the pro‐inflammatory response, then accelerates M1‐to‐M2 macrophage polarization transition, yielding a satisfactory pattern of osteo‐immunomodulation during the natural bone healing process. Later, sustained release of Zn2+/Sr2+ ions with gradual degradation of the 3D scaffold maintains the favorable reparative M2‐dominated immunological microenvironment that supports new bone mineralization. Precise temporal immunoregulation of the bone healing process by the intelligent 3D scaffold enhances bone regeneration in a rat cranial defect model. This strategy paves the way for the application of β‐tricalcium phosphate‐based materials to guide the dynamic inflammatory and bone tissue responses toward a favorable outcome, making clinical treatment more predictable and durable. The findings also demonstrate that near‐infrared irradiation‐derived mild hyperthermia is a promising method of immunomodulation.