ポリフェノール由来ナノアーマー機能化フォトサーマルハイドロゲルプラットフォームによる再生微小環境および骨欠損治癒のプログラム制御

The development of an intelligent, responsive therapeutic system capable of orchestrating highly ordered tissue regeneration has emerged as a promising strategy for the treatment of diabetic bone defects. Herein, natural polyphenol-derived black phosphorus (BP)-based multifunctional hydrogels are elaborately designed to work in conjunction with mild photothermal therapy for programmed regulation of the bone regeneration microenvironment through on-demand antioxidation, anti-inflammation, immunomodulation, and angiogenesis-osteogenesis coupling. Inspired by metal-phenol coordination chemistry, we constructed a novel metal-phenolic network system as a "multifunctional armor" for traditional BP nanosheets. In vitro biological experiments and RNA sequencing analysis demonstrated that polyphenol-derived BP nanosheets with remarkable osteogenic, reactive oxygen species (ROS)-scavenging, and anti-inflammatory properties could remodel the immune microenvironment and alleviate oxidative stress by regulating multiple inflammation-related signaling pathways. Upon uniform cross-linking with biocompatible hydrogels, the resulting hybrids exhibited a porous microstructure resembling that of a bone extracellular matrix, along with outstanding injectability, biodegradability, improved mechanical properties, and excellent photothermal effects. Moreover, the combined effects of polyphenol functionalization and mild heat stimulation enable exceptional performance in fostering anti-inflammation, angiogenesis, and osteogenesis in a spatial and temporal manner. Collectively, these findings highlight the promising application prospects of such polyphenol-derived multifunctional hydrogel platforms for complex bone defect healing and reconstruction.