3D Printed Graphene Oxide/Calcium Alginate/Strontium-Doped Hydroxyapatite Composite Scaffolds with Enhanced Osteogenic and Angiogenic Properties for Critical-Size Bone Defect Repair

The repair of critical-sized bone defects is hindered by insufficient vascularization, an unfavorable osteogenic microenvironment, and the limitations of conventional materials. Systematic studies on ternary composites of graphene oxide (GO), calcium alginate (CA), and strontium-doped hydroxyapatite (Sr-HA) remain limited, particularly regarding how different strontium substitution levels influence scaffold rheology, mechanics, ion release, osteogenic activity, and vascular-associated responses. Here, graphene oxide/calcium alginate/strontium-doped hydroxyapatite scaffolds (3D GCHs) were fabricated via direct ink writing (DIW) with systematically controlled strontium substitution levels. All inks exhibited excellent shear-thinning behavior. The scaffolds showed a regular porous morphology and uniform strontium incorporation within the hydroxyapatite lattice. Notably, among the tested formulations, 3D GCH10 achieved a compressive stress of 3.42 ± 0.03 MPa at 70% strain and sustained Sr²⁺/Ca²⁺ release for 28 d. In vitro, 3D GCH10 promoted BMSC proliferation, upregulated ALP, OPN, and RUNX2, enhanced mineralization, and showed no cytotoxicity. In a rat cranial defect model, BV/TV increased by 214.35% versus the blank group, with superior new bone formation, collagen deposition, and CD31/α-SMA-positive vascular density. These results suggest that appropriate strontium substitution combined with GO and CA contributes to improved scaffold properties and enhanced bone regeneration, highlighting the potential of 3D GCH10 for bone tissue engineering.