Ectopic mineralization-inspired cell membrane-based matrix vesicle analogs for in-depth remineralization of dentinal tubules for treating dentin hypersensitivity

The invasion of etched dentinal tubules (DTs) by external substances induces dentin hypersensitivity (DH). The deep and compact occlusion of DTs is highly desirable for treating DH but still challenging due to the limited penetrability and mineralization capacities of most current desensitizers. Matrix vesicles (MVs) participate in the regulation of ectopic mineralization. Herein, ectopic MV analogs are prepared by employing natural cell membranes to endow mineral precursors with natural biointerfaces and integrated biofunctions for stimulating dentin remineralization. The analogs quickly access DTs (> 20 µm) in only 5 min and further penetrate deep into the interior of DTs (an extraordinary ∼ 200 µm) in 7 d. Both in vitro and in vivo studies confirm that the DTs are efficiently sealed by the newly formed minerals (> 50 µm) with excellent resistance to wear and acid erosion, which is significantly deeper than most reported values. After repair, the microhardness of the damaged dentin can be recovered to those of healthy dentin. For the first time, cell membrane coating nanotechnology is used as a facile and efficient therapy for in-depth remineralization of DTs in treating DH with thorough and long-term effects, which provides insights into their potential for hard tissue repair.