Enhanced Osteointegration of PEEK Implants Through Dual Surface Modification - PROJECT SUMMARY This project aims to address a critical barrier in orthopedic implant performance by enhancing the osteointegration of polyetheretherketone (PEEK), a clinically promising yet biologically inert material. While PEEK offers favorable mechanical properties, radiolucency, and biocompatibility, its lack of bioactivity and tendency to provoke pro-inflammatory immune responses limit its long-term clinical success. The proposed research introduces a novel, dual-function surface modification strategy that integrates precisely controlled microscale porosity with a bioactive mineralized collagen coating embedded with microRNA-26a (Coll/HA–miR- 26a). This innovative approach is designed to replicate the microarchitecture of native bone resorption pits, support osteoblast attachment and differentiation, and modulate macrophage polarization toward the regenerative M2 phenotype. The project is structured around three interrelated aims: In Aim 1 we will fabricate and characterize modified PEEK implants using NaCl leaching to generate osteoclast-inspired microscale porosity, followed by low-temperature adsorption of Coll/HA–miR-26a to create a bioactive and immunomodulatory surface. In Aim 2, we will evaluate osteoblast response to the modified surfaces, focusing on miR-26a uptake, proliferation, osteogenic differentiation, and activation of Wnt/β-catenin signaling. In Aim 3, we will assess macrophage adhesion, phenotype polarization, and cytokine expression, with an emphasis on suppressing M1-driven inflammation and promoting M2-mediated tissue regeneration. Mechanistic studies will elucidate how the dual-modified surface influences osteoimmune crosstalk, offering insight into the biological pathways critical for implant integration. The expected outcomes will establish a scalable and translationally viable surface engineering platform for next-generation PEEK implants, particularly suited for patients with impaired bone healing due to aging, diabetes, or inflammation-related conditions. Moreover, the project will serve as a robust educational platform, engaging medical students, residents, and undergraduates in cutting-edge interdisciplinary research at the interface of materials science, immunology, and regenerative medicine.