The effect of recombinant VEGF and merwinite nanoparticles within a 3D-printed scaffold containing hyaluronic acid-fucoidan on craniofacial osteoangiogenesis

Abstract

Craniofacial fractures present intricate geometries that require defect-matched scaffolds for effective regeneration. Advanced 3D printing enables the fabrication of anatomically tailored structures, making it a powerful tool in bone tissue engineering. In this study, a novel 3D-printed scaffold integrating polyvinyl alcohol (PVA), hyaluronic acid (HA), fucoidan (Fc), and merwinite (Mr) nanoparticles with recombinant VEGF was developed as a multifunctional platform, with the aim of promoting both osteogenesis and angiogenesis in complex craniofacial defects. The HA.Fc.VEGF.Mr scaffold exhibited a compressive strength of 3.19 +/- 0.11 MPa and an elastic modulus of 21.75 +/- 3.32 MPa, making it suitable for craniofacial bone repair. After 28 days of immersion in PBS, the scaffold showed a degradation rate of 50.6 +/- 4.6 , while VEGF release reached 95.1 +/- 5.1 in a sustained, linear pattern by day 11. Bioactivity was validated through apatite-like deposition in SBF immersion for 28 days, alongside measurable release of Ca(2+), Si(4+), and Mg(2+) ions. In vitro assessments demonstrated high cytocompatibility and enhanced osteogenic activity, confirmed by ALP levels, calcium deposition, and the upregulation of COL1, RUNX2, and osteocalcin. Angiogenic potential was further validated using the CAM assay, where the HA.Fc.VEGF.Mr scaffold exhibited superior neovascularization compared to other groups. These findings demonstrate the multifunctionality and regenerative potential of this scaffold for craniofacial bone repair.