Three-step crosslinking dependent self-bending transformation of a nano-spherical mineralized collagen laden 4D printed sodium alginate scaffold for bone regeneration.

Although 3D printed scaffolds are widely used in irregularly shaped bone defects, additional steps often need to be introduced when fabricating structures with curvature. In contrast, 4D printing has a unique advantage in the fabrication of scaffolding with a curved structure. Bone defects such as skull is generally curved, so a self-bending scaffold would be more appropriate for the cranial defect site. This paper presents a novel self-bending SAGMA hydrogel was loaded with nano-spherical mineralized collagen, then fabricated by a 4D printing method, which achieves adjustable self-bending through three-step crosslinking. When subjected to UV light irradiation, variations in gradient of photo-crosslinking are induced within the scaffold. This gradient of photo-crosslinking serves as the foundation for the scaffold's self-bending. The scaffold exhibited self-bending after crosslinking with calcium ions and chitosan, respectively, with curvature ranging from 0.05 mm to 0.446 mm. In vivo experiments demonstrated the efficacy of the scaffold in enhancing the repair of cranial bone defects and promoting new bone formation in rats, as evidenced by microcomputed tomography and histochemical analysis. Therefore, this self-bending scaffold provides a potentially effective method for the clinical treatment of skull defects with curvature.