3D-Printed Scaffolds for Cranial Bone Regeneration: A Systematic Review of Design, Materials, and Computational Optimization.

Cranial bone defects from trauma, congenital conditions, or surgery are challenging to treat due to the skull's limited regeneration. Traditional methods like autografts and allografts have drawbacks, including donor site issues and poor integration. 3D-printed scaffolds provide a patient-specific alternative, improving bone regeneration and integration. This review evaluates advancements in 3D-printed scaffolds for cranial bone regeneration, focusing on fabrication techniques, material innovations, and structural optimization while assessing their preclinical and clinical potential. A systematic literature search (2014-2024) was conducted using PubMed and other databases. Studies addressing scaffold properties such as porosity, pore interconnectivity, and mechanical stability were included, while non-cranial scaffold studies were excluded. Advances in 3D printing have enabled patient-specific scaffolds with optimized architecture to enhance bone regeneration, mechanical support, and nutrient transport. Bioceramics, polymers, and composites mimic native bone properties, while bioactive coatings further improve osteogenesis. However, limited clinical translation and insufficient customization remain challenges. Further preclinical and clinical trials are crucial to overcoming barriers in mechanical optimization and patient-specific scaffold fabrication, bridging the gap between research and clinical applications.