3D-Printed Vancomycin-Loaded ZIF-8@GMP Scaffolds with Sustained Antibacterial, Anti-Inflammatory, and Osteoinductive Properties for Bone Tissue Engineering

Gelatin-based hydrogels have garnered significant attention in bone tissue engineering due to their excellent biocompatibility and ease of processing. However, their inherent limitations, such as poor mechanical strength and weak anti-inflammatory and antibacterial properties, restrict their broader application. To overcome these challenges, we developed a multifunctional 3D-printed scaffold by in situ growth of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles within a creatine phosphate and methacrylic anhydride-modified gelatin matrix (GMP, methacrylation degree: 52.00%, creatine phosphate grafting rate: 17.89%), followed by vancomycin (VAN) loading. The resulting VAN/ZIF-8@GMP scaffolds exhibited prominent sustained drug release (78.89% VAN released at 96 h, vs 94.42% for direct blending scaffolds), enhanced antibacterial activity with 100% inhibition rate against both <i>Escherichia coli</i> (MIC = 32 μg/mL) and <i>Staphylococcus aureus</i> (MIC = 2 μg/mL), and improved mechanical properties (compressive strength: 192 kPa). The incorporation of ZIF-8 with pH-responsive Zn²⁺ release endows the scaffolds with anti-inflammatory effects (reducing protein denaturation by ∼26% at 72 h) and osteogenic stimulation. <i>In vitro</i> assays confirm their better antibacterial performance against Gram-positive bacteria, support MC3T3-E1 cell proliferation, and promote mineralization with significantly increased alkaline phosphatase (ALP) activity during 21 days of osteogenic induction. This multifunctional scaffold provides a promising strategy for infection prevention and bone regeneration in orthopedic applications.