A spatiotemporally programmed bioactive scaffold for orbital reconstruction

Orbital implants are widely used for post-enucleation reconstruction, but poor fibrovascularization and infection risk still limit their clinical performance. Herein, a three-dimensional (3D)-printed copper-doped hardystonite (HT, Ca₂ZnSi₂O₇) scaffold with polar-graded porosity is developed for spatiotemporally programmed orbital reconstruction. By matching the intrinsic orbital regenerative trajectory, small pores promote early immunomodulation and reparative-cell recruitment, medium pores enhance angiogenic activation, and large pores facilitate vascular ingrowth and vascular-network assembly. This design drives a sequential regenerative process involving immune modulation, endothelial activation, interfacial remodeling, and vascular assembly. In rabbit aseptic and infected models, the implant promotes ordered fibrovascularization and suppresses bacterial colonization, showing superior performance to clinical hydroxyapatite implants. Taken together, this study presents a spatiotemporally programmed bioactive scaffold as a promising strategy for orbital reconstruction.