Enhancing the osteogenic potential of 3D-printed polycaprolactone/hydroxyapatite composite scaffolds via in-situ ZIF-8 surface modification

Abstract Bone defects remain a major clinical challenge, necessitating advanced scaffolds that combine suitable mechanics, bioactivity, and osteoinductive cues for effective regeneration. This study developed 3D-printed polycaprolactone/hydroxyapatite (PCL/HA) composite scaffolds via fused deposition modeling and enhanced their surface with in-situ zeolitic imidazolate framework-8 (ZIF-8) modification to promote osteogenic performance. Hydrothermally synthesized HA nanoparticles exhibited high crystallinity, <100 nm size, and ~23 m²/g specific surface area. The optimal PCL + 25 wt.% HA composition achieved a compressive modulus of ~0.36 GPa and strength of ~17 MPa, within the range reported for human trabecular bone. The scaffolds demonstrated controlled biodegradation ( ~ 15% weight loss after 28 days in PBS) and strong bioactivity, with progressive apatite mineralization confirmed by SEM, XRD, and ion concentration changes in simulated body fluid over 28 days. ZIF-8 surface functionalization enabled sustained, non-burst Zn²⁺ release (0.18–1.66 ppm over 28 days) within safe biological limits. In vitro assays using MG-63 cells showed significantly improved cell adhesion, proliferation (MTS assay), and osteogenic differentiation on ZIF-8-modified scaffolds compared to unmodified controls, evidenced by 2.1-fold higher alkaline phosphatase (ALP) and 2.5-fold higher BMP2 gene expression after 21 days of induction. These results demonstrate that the synergistic combination of HA reinforcement and controlled Zn²⁺ release from ZIF-8 provides a multifunctional scaffold platform for bone regeneration.