Zinc and metformin co-functionalized polyetheretherketone: A novel dental implant material tailored for the elderly

INTRODUCTION: The rising demand for dental implants among the elderly population is challenged by age-related impairments in osteogenic regeneration, such as Wnt/β-catenin signaling decline, ROS-mediated cellular senescence (compromising osteoblast differentiation), and elevated pro-inflammatory cytokines (e.g. IL-6, TNF-α). Senescent osteoblasts establishes a pathological triad: (1) cell-cycle arrest-mediated osteogenic impairment, (2) SASP-fueled chronic inflammation, and (3) immune-bone uncoupling-collectively driving alveolar bone deterioration in the elderly. Polyetheretherketone (PEEK), with its elastic modulus similar to that of alveolar bone, emerges as a promising implant material. However, its bioinert nature limits its osseointegration capabilities. OBJECTIVES: This study aimed to develop a functionalized PEEK derivative, ZnMet@PEEK, by integrating zinc (Zn) and metformin (Met) into PEEK. to enhance osseointegration with alveolar bone in elderly patients. METHODS: In this study, we combined the anti-inflammatory and osteogenic properties of Zn with the anti-senescence effects of Met using dopamine-assisted physical adhesion to prepare ZnMet@PEEK, aiming to enhance PEEK's osseointegration with alveolar bone in elderly patients. We examined the biocompatibility and osteoblast differentiation-inducing ability of ZnMet@PEEK in vitro by CCK8, live/dead cell staining, RT-qPCR, immunofluorescence staining and Enzyme-Linked Immunosorbent Assay for osteogenesis-related proteins. Further, we constructed an animal model and detected the bone regeneration ability of ZnMet@PEEK in vivo by micro-CT and histological analysis. RESULTS: Material characterization confirmed the incorporation of ZnMet onto PEEK. in vitro and in vivo evaluations demonstrated that ZnMet@PEEK exhibited excellent biocompatibility, significantly inhibited inflammation, promoted bone formation, and inhibited cellular senescence, ultimately resulting in enhanced osseointegration in aged rats. CONCLUSIONS: In this study, we successfully developed a new functionalized PEEK derivative, ZnMet@PEEK, with tailored bioactivities including anti-inflammatory, osteogenic, and anti-senescence properties, as a dental implant for the elderly population. Therefore, we believe that ZnMet@PEEK, specifically tailored for elderly patients, is a promising dental implant material offering a novel solution to the multifaceted challenges of osseointegration.