Simvastatin and Moxifloxacin Co-Delivery via ZIF-8/PDA Coating on PEEK Implants: A Strategy for Combating Implant-Associated Infection and Enhancing Osseointegration

Zidong Wu,1,* Kai Ma,1,2,* Zixuan Wu,1,* Xiaoyu Guo,1 Yuning Qu,1 Zheyue Zhu,1 Weidong Zhu,1,3 Chengxin Li,2 Yi Liu,1,2 Rui Ma,1 Pei Yang1 1Joint and Foot & Ankle Ward of Orthopedic Center, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, People’s Republic of China; 2State Key Laboratory for Mechanical Behavior of Materials, School of Materials Science and Engineering, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 3Department of Spinal Surgery, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Ma; Pei Yang, Email shandongmarui@126.com; yangpei@xjtu.edu.cnBackground: Polyetheretherketone (PEEK) is a promising orthopedic implant material due to its bone-matched elastic modulus and radiolucency. However, its clinical application is limited by biological inertness and lack of antibacterial activity, which predispose to implant-associated infection (IAI) and poor osseointegration. This study developed a multifunctional coating on sulfonated PEEK (SPEEK) via polydopamine (PDA)-mediated co-delivery of simvastatin-loaded ZIF-8 nanoparticles (SIM@ZIF-8) and moxifloxacin (MOX) to address these limitations.Methods: A time-programmed release coating was fabricated on SPEEK by embedding SIM@ZIF-8 within a PDA layer and surface-loading MOX onto the surface. The coating’s physicochemical properties, drug release profiles, biocompatibility, antibacterial activity, and osteogenic capacity were evaluated in vitro. Antibacterial efficacy and osseointegration were further assessed in vivo using rat subcutaneous infection and rabbit femoral defect models.Results: Release profiles revealed that MOX exhibited burst release within 24 h, whereas SIM quickly reached therapeutic concentrations during the initial phase and was slowly released over five weeks, while Zn2+ from ZIF-8 was released synchronously with SIM. In vitro antimicrobial assays showed that the synergistic release of MOX and SIM exhibited potent antibacterial activity against Staphylococcus aureus and Escherichia coli, providing sustained inhibition of Staphylococcus aureus biofilms. The coating also promoted MC3T3-E1 cell adhesion, spreading, and osteogenic differentiation, as indicated by upregulated osteogenic markers (Runx2, OCN, OPN, COL1A1), enhanced matrix mineralization, and increased BMP-2 expression. In rat models, bacterial colonization on the coated surface and residual bacteria in tissues were significantly reduced. In rabbit femoral defects, sustained co-release of SIM and Zn2+ accelerated new bone formation and improved osseointegration, confirmed by micro-CT, double fluorescence labeling, and histological analysis.Conclusion: This study presents a novel bioactive PEEK implant coating integrating antibacterial and osteogenic functions through a MOX/SIM@ZIF-8/PDA system. The strategy effectively combats IAI and enhances osseointegration, offering potential for clinical orthopedic applications.Keywords: polyetheretherketone, antibacterial coating, osseointegration, simvastatin, drug delivery