Vascularization and Bone Regeneration with 3D-Printed Composite Scaffolds in Rodent Critical-Size Calvarial Defects:...

Rapid vascularization is essential for bone regeneration in oral and maxillofacial surgery. This systematic review synthesised in vivo evidence on 3D-printed composite scaffolds in rodent critical-size calvarial defects quantified by Microfil perfusion and micro-CT. "Composite" was defined as an organic-inorganic construct within the printed scaffold (not a single-phase scaffold with a surface coating). PubMed, MEDLINE, and Web of Science Core Collection were searched for studies published from January 2014 to December 2025. Eligible studies compared composite scaffolds with non-composite (single-phase) scaffolds and/or empty controls and reported vascular outcomes (vessel number, vascularized area) together with bone outcomes (new bone area, bone volume fraction [BV/TV], and bone mineral density). Ten studies met the inclusion criteria. In outcome-specific exploratory analyses, composite scaffolds were associated with higher new bone area than comparators (p = 0.031). Functional modifications were associated with higher vascularized area (p = 0.025) and higher new bone area (p = 0.038), while dual-factor modifications showed the largest gain in new bone area (p = 0.002). Pore sizes ≥ 400 μm were associated with higher BV/TV (p = 0.029). Heterogeneity in designs, follow-up, and reporting, together with small sample sizes, precluded meta-analysis. Composite scaffolds appear promising, but standardised methodologies and improved reporting are needed to define optimal design features and support translation.