Surficial Pore Structure on Polyetheretherketone Implants Regulates Mechanical Properties to Promote Macrophage M2 Polarization

The surficial micro–nanostructure on polyetheretherketone (PEEK) can increase the biocompatibility of biomaterials and promote macrophage M2 polarization to induce soft tissue integration. However, because it is difficult to obtain a uniform and controllable surficial micro–nanostructure on PEEK, the regulation rules and underlying mechanisms for macrophage M2 polarization remain poorly understood. In this study, we used a hot pressing technique to fabricate uniform submicrometer porous structures with sizes of 200, 500, and 800 nm on PEEK material. These structures can significantly increase the hydrophilicity of the interface and decrease the stiffness of the materials. Furthermore, a cellular experiment was performed to investigate the optimal size of the submicrometer structure for macrophage M2 polarization, and 200 nm pores on PEEK can significantly promote macrophage polarization toward the reparative M2 phenotype, accompanied by increased secretion of cytokines such as TGF-β1 and Arg1. Indirect coculture assays further confirmed that these polarized macrophages enhanced the proliferation and migration of vascular endothelial cells and fibroblasts. Transcriptomic analysis and molecular biology experiments revealed that the 200 nm porous interface can lead to downregulation of Piezo1, Yap1, and NF-κB and upregulation of STAT6 and TGF-β1 in the process of macrophage M2 polarization. Moreover, the C57 mouse experiment showed the improved soft tissue integration surrounding the PEEK implants with 200 nm pores, accompanied by better vascularization and fibrosis. This study highlights that 200 nm porous PEEK implants can modulate macrophage M2 polarization to promote soft tissue integration, and this process relies on the activation of the Piezo1/TGF-β1 signaling pathway.