4D printed hydrogel scaffolds with shape morphing by near-infrared to promote bone regeneration through immune and vascular coupling

The regeneration of critical-size irregular bone defects, especially those with irregular shapes, remains clinically challenging due to inadequate shape-conformability, immune dysregulation, poor vascularization and the unsatisfied osteogenic bioactivity. Self-fitting tissue scaffolds that can be implanted by minimally invasive procedures are a promising solution. Herein, we present a 4D-printed hydrogel scaffold (PASN) composed of polydopamine (PDA), alginate (Alg), and strontium ions (Sr²⁺), that is 3D-printed and NIR-induced shape-morphing to match defect and orchestrate both immunomodulation and osteogenesis. By eliminating reactive oxygen species and driving M2 macrophage polarization through PDA, PASN improves immune regulation through the PI3K signaling pathway as well as stimulates osteogenesis and angiogenesis through release of Sr²⁺. The deformation angle of the scaffold is adjusted by the laser power, irradiation time, and the designed pattern of alginate PDA struts, whereas the temperature gradient formed between the upper and lower layers under NIR irradiation induces bending toward the light source. Dome-shaped calvarial defects, maxillary sinus floor lift and horizontal bone augmentation surgeries demonstrate the PASN scaffold markedly enhances bone regeneration. Collectively, the personalised and bioactive scaffold with NIR-responsive shape-morphing may be a promising biomaterial for clinical-size and irregular bone defect regeneration.