A Novel Polyetheretherketone–Chondroitin Sulfate Zinc Composite: Enhancing Osseointegration through the Synergistic Effects of Chondroitin Sulfate and Zinc for Advanced Dental Implant Applications

<i>Background</i>: Polyetheretherketone (PEEK) is a promising alternative to titanium alloy for dental implants due to its bone-mimicking elastic modulus, which mitigates stress shielding. However, its bioinert nature limits osseointegration. <i>Methods</i>: We developed a novel PEEK variant, PEEK-chondroitin sulfate zinc (PEEK-CSZn), by chemically grafting zinc and chondroitin sulfate onto the PEEK surface. Material properties were characterized using SEM, FTIR, EDS, and ICP-MS. Anti-inflammatory, osteogenic, and angiogenic effects were evaluated in <i>vitro</i> using MC3T3-E1, HUVEC, and RAW264.7 cells and in vivo using a rabbit femur bone defect model. <i>Results</i>: Characterization confirmed successful CSZn integration. <i>In</i> <i>vitro</i>, PEEK-CSZn at 500 μg/mL enhanced the MC3T3-E1 cell proliferation. Osteogenic markers (OCN and Osterix) were upregulated by around 2.3- and 1.8-fold, respectively, in MC3T3-E1 cells (<i>p</i> < 0.05). Inflammatory markers (IL-6 and IL-12a) in RAW264.7 cells decreased by 23% and 49%, respectively (<i>p</i> < 0.05), while angiogenic markers (VEGF and CD31) in HUVECs increased by 2.2- and 2.8-fold (<i>p</i> < 0.05). In <i>vivo</i>, Micro-CT analysis revealed PEEK-CSZn increased bone volume fraction (BV/TV) and BMD compared to unmodified PEEK at 8 weeks postimplantation (<i>p</i> < 0.05). <i>Conclusions</i>: PEEK-CSZn exhibits trifunctional bioactivities, including anti-inflammatory, osteogenic, and angiogenic, and thus significantly enhances osseointegration, making it a promising material for advanced dental implant applications.