Abstract: Recent advances in bone regeneration have introduced the concept of four-dimensional (4D) scaffolds that can undergo morphological and functional changes in response to external stimuli. While several studies have proposed patient-specific designs for defect sites, they often fail to adequately distinguish the advantages of 4D scaffolds over conventional 3D counterparts. This study aimed to investigate the potential benefits of 4D scaffolds in clinically challenging scenarios involving curved defects, where fixation is difficult. We proposed the use of Shape-Memory Polymers (SMPs) as a solution to address critical issues in personalized scaffold fabrication, including dimensional accuracy, measurement error, and manufacturing imprecision. Experimental results demonstrated that the Curved-Layer Fused Deposition Modeling (CLFDM) scaffold, which offers superior conformability to curved defects, achieved significantly higher interfacial contact with the defect area compared to traditional Fused Deposition Modeling (FDM) scaffolds. Specifically, the CLFDM scaffold facilitated bone regeneration of 25.59?±?4.72 mm3, which is more than twice the 9.37?±?1.36 mm3 observed with the 3D FDM scaffold. Furthermore, the 4D CLFDM scaffold achieved 75.38?±?11.65 mm3 of new bone formation after four weeks, approximately three times greater than that of the 3D CLFDM scaffold, regardless of surface micro-roughness. These results underscore that improved geometrical conformity between the scaffold and the defect site enhances cellular infiltration and contributes to more effective bone regeneration. The findings also highlight the promise of 4D scaffolds as a compelling strategy to overcome geometric and dimensional mismatches in the design of patient-specific scaffolds.

Key words: Additive manufacturing')">Additive manufacturing, Bone regeneration efficacy, 4D scaffold, Shape conformity, 3D curved defect