Near-Infrared Responsive Property and Nanozyme Effect-Mediated 3D-Printed Gradient Bioactive Scaffold for Intelligent...

Regeneration of large segmental bone defects remains a formidable challenge, mainly due to the lack of a supportive microenvironment for the host's intrinsic repair cascade. Although 3D-printed porous calcium phosphate ceramics have osteoconductive properties, their inability to actively regulate key immune processes and compromised mechanical strength caused by porosity greatly limit therapeutic efficacy. Herein, an "osteoimmunology"-informed design of a near-infrared (NIR)-responsive 3D-printed gradient scaffold is proposed for intelligent bone regeneration by temporally modulating macrophage phenotypic polarization. Fabricated via digital light processing (DLP) printing combined with secondary sintering, this scaffold has a core-shell-like gradient structure (dense interior, porous exterior), achieving a balanced combination of mechanical robustness and bioactivity. Manganese iron Prussian blue analogue (MnFePBA) nanozymes were incorporated onto the scaffold surface. Under NIR irradiation, MnFePBA not only scavenges excessive reactive oxygen species (ROS) but also triggers controlled release of Mn^{2 +}, synergistically driving macrophages to polarize from proinflammatory M1 to proregenerative M2 phenotype. In vitro and in vivo studies confirm that the scaffold alleviates post-implantation oxidative stress, fosters a favorable immune microenvironment, and significantly enhances bone repair, establishing a new paradigm for developing next-generation smart bone grafts via active immunomodulation.