Personalized Pliable and Trimmable Hydrogel-Derived Bioceramic Scaffolds for Cranial Bone Regeneration

Conventional critical-sized bone defect (CSD) implants frequently suffer from geometric mismatches and interfacial gaps with the host bone, leading to suboptimal osteogenesis and poor osseointegration. Herein, inspired by kirigami and origami concepts, we propose a novel approach for fabricating bioceramic scaffolds from pliable, trimmable hydrogel-based ceramic precursors composed of photosensitive hydrogel components and nano-hydroxyapatite. The hydrogel precursor exhibits superior ductility and elasticity, enabling convenient tailoring to the contours of complex bone defects, such as cranium. After sintering, the hydrogel-derived bioceramic scaffolds exhibit ultra-low linear shrinkage (∼10%), well-defined structural fidelity, and moderate mechanical properties. In vitro experiments confirmed that the bioceramic scaffolds possess superior biocompatibility and promote osteogenic differentiation, as evidenced by the upregulation of osteogenic genes (Runx2, Alp, Ocn, and Col I). In a rat CSD model, Micro-CT and histological analyses demonstrated that the hydrogel-derived bioceramic scaffolds promoted substantial new bone formation compared with the control group, which was further corroborated by immunohistochemical staining showing upregulated expression of osteogenic-related proteins, including RUNX2, OPN, and OCN. Overall, this work provides a viable strategy for fabricating bioceramic scaffolds that match the geometric contours of bone defects while effectively promoting bone regeneration.