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

TL;DR

This review examines how 3D-printed composite scaffolds improve blood vessel growth and bone regeneration in rodent skull defects.

Contribution

The study systematically evaluates composite scaffolds using specific vascular and bone regeneration metrics in critical-size calvarial defects.

Findings

Composite scaffolds showed higher new bone area compared to controls (p = 0.031).

Functional modifications increased vascularized area and new bone area (p = 0.025 and p = 0.038).

Pore sizes ≥ 400 μm were linked to higher bone volume fraction (p = 0.029).

Abstract

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.

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