Regulation of T Cell Glycosylation by MXene/β‐TCP Nanocomposite for Enhanced Mandibular Bone Regeneration

Abstract Immune‐mediated bone regeneration driven by bone biomaterials offers a therapeutic strategy for repairing bone defects. Among 2D nanomaterials, Ti 3 C 2 T x MXenes have garnered substantial attention for their potential in tissue regeneration. This investigation concentrates on the role of MXene nanocomposites in modulating the immune microenvironment within bone defects to facilitate bone tissue restoration. Ti 3 C 2 T x MXenes are synthetized, incorporated into beta‐tricalcium phosphate ceramics (β‐TCP) nanocomposites (T‐MXene), and their osteoinductive and immunomodulatory effects are evaluated. The effects of T‐MXene‐treated T‐cells on bone marrow stromal cells (BMSCs) are explored. In addition, its therapeutic potential for bone regeneration is assessed in vivo using a critical‐sized mandibular bone defect model. The underlying mechanisms by which T‐MXene regulates T‐cell differentiation and bone regeneration are explored via whole‐transcriptome RNA sequencing. The scaffolds activate N‐glycosylation in T cells, which possess anti‐inflammatory and antioxidant effects, thereby inducing a pro‐regenerative response. T‐MXene increased the proportion of IL‐4 + T cells among primary T cells and mandibular lymph nodes, ultimately promoting osteogenesis in BMSCs and injured mandibles. The distinctive function of MXene‐based nanocomposites in osteoimmunomodulation provides a solid foundation for further exploration and application of MXenes as immune response modulators, potentially advancing their use in regenerative medicine.