Polyetheretherketone (PEEK) is an attractive orthopedic implant material due to its bone-matched elastic modulus, chemical stability, and low toxicity. However, its bioinertness and poor osseointegration limit its clinical application, activating inflammatory responses and causing fibrous encapsulation. To address these issues, we designed a polydopamine (PDA)-assisted coating on sulfonated PEEK (SP) that released cytokines and drugs to regulate the immune response and promote osteogenesis. We constructed a bio-self-assembled apatite (Ap) layer via simulated body fluid (SBF) immersion, followed by PDA-mediated deposition of dexamethasone (DEX)-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles and the surface adsorption of interleukin-4 (IL-4). The SP-Ap-DEX@ZIF-8-PDA-IL4 construct released IL-4 within 7 days and DEX within 28 days, while releasing calcium and zinc ions. The coating promoted the adhesion, spreading, and osteogenic differentiation of MC3T3-E1 cells. The coating polarized macrophages toward an anti-inflammatory M2 phenotype, suppressing pro-inflammatory cytokines while increasing anti-inflammatory cytokines. Results showed that macrophage-conditioned medium promoted osteodifferentiation, and RNA sequencing (RNA-Seq) indicated that the coating inhibited pro-inflammatory NF-κB signaling while activating the cGMP-PKG pathway. The rat air pouch model demonstrated that the coating inhibited inflammation and reduced fibrous capsule formation by promoting M2 macrophage polarization and inhibiting M1 polarization. An in vivo study using a rabbit femoral defect model showed that the coating accelerated new bone deposition and improved osseointegration. This study presents a temporal release strategy that integrates early immunomodulation with long-term osteogenic stimulation of PEEK implants, offering potential for bioactive orthopedic implants. • Bioactive Coating Design: A dual-drug-functionalized coating was constructed on sulfonated PEEK using Polydopamine and zeolitic imidazolate framework-8 (ZIF-8) as carriers for IL-4 and dexamethasone (DEX), enabling time-series release. • Anti-Inflammatory & Osteogenic Synergy: Through early release of IL-4 and long-term release of DEX, the coating promoted osteogenic differentiation and M2 macrophage polarization, inhibited NF-κB signaling, and enhanced cGMP-PKG pathway activation • In Vivo Efficacy: The coating showed significant anti-inflammatory effects in the rat air bag model, and showed excellent osseointegration and bone repair capabilities in the rabbit femoral defect model. • Modular Platform: The study realized the active guidance of bone repair materials on the physiological process of bone repair, and provided a new strategy for the development of intelligent bone implant materials with immune osteogenesis regulation function.
Wu et al. (Sun,) studied this question.