Multifunctional Hydrogel with Synergistic Reactive Oxygen Species Scavenging and Macrophage Polarization-Induced Osteo-immunomodulation for Enhanced Bone Regeneration
Qingcheng Song, Yiran Zhang, Yiran Zhang, Hongzhi Hu, Xing Xin, Jianhua Wu, Yanbin Zhu, Wei Chen, Yingze Zhang, Yingze Zhang
Abstract
The regeneration of bone defects remains an enormous clinical challenge owing to locally abnormal reactive oxygen species (ROS) levels and the inability to timely regulate the osteoimmune microenvironment. Herein, polydopamine (PDA) modified black phosphorus nanosheets (BP) with small palladium nanoparticles (Pd NPs) immobilized in situ were prepared (BP@PDA-Pd) and incorporated into a gelatin methacryloyl/methacrylated poly-γ-glutamate hybrid hydrogel to fabricate a composite photocurable therapeutic platform (BPPP/GP) with excellent antioxidant and osteo-immunomodulatory activity for enhanced high-quality endogenous bone regeneration. The BPPP with optical absorbance in the near-infrared (NIR) region endows the composite hydrogel with excellent NIR-responsive characteristics, resulting in mild photothermal-enhanced antioxidant enzyme-like activity to scavenge ROS and the induction of endogenous cell recruitment. More importantly, the BPPP/GP photocurable hydrogel with mild photothermal stimulation could achieve spatiotemporal regulation of the osteoimmune microenvironment by inducing macrophage polarization toward the anti-inflammatory phenotype (M2), with the secretion of pro-osteogenic and pro-angiogenic growth factors. In vivo experiments confirmed that the NIR-stimulation based BPPP/GP system could effectively eliminate ROS, alleviate local inflammation, and regulate macrophage polarization to create a favorable osteoimmune microenvironment for osteogenic differentiation and revascularization. Together, the development of this multifunctional hydrogel with the capability to reshape the damaged microenvironment provides a promising strategy for accelerating bone regeneration.