Superior Synergistic Osteogenesis of MXene-Based Hydrogel through Supersensitive Drug Release at Mild Heat

Near-infrared (NIR) responsive smart drug delivery systems could provide efficient osteogenesis through the synergy of heat and drugs. However, such systems are hampered by an inability to allow supersensitive drug release through mild heat. Here superior osteogenesis is demonstrated using a biocompatible dexamethasone (Dex)-loaded MXene-poly(N-isopropylacrylamide)-co-N-(Hydroxymethyl) acrylamide hydrogel capable of the supersensitive release of Dex at ≈42 °C upon NIR irradiation. Furthermore, the hydrogel can significantly promote bone regeneration under NIR irradiation due to the synergistic anti-apoptosis and osteogenic differentiation of bone-derived mesenchymal stem cells induced by the mild heat and supersensitive release of Dex. The resulting osteogenesis efficiency of hydrogels surpass efficiencies previously reported for heat and drug stimulation and their combination. The synergistic osteogenesis strategy is characterized by near-instantaneous, noninvasive, and precise treatment through temporal NIR irradiation.