Hierarchical Micro-/Nanotopographical Cues on Polyether–Ether–Ketone Implants for Enhanced Osteogenesis and Angiogenesis

Polyether–ether–ketone (PEEK) has emerged as a promising alternative to titanium for orthopedic applications due to its excellent biocompatibility and mechanical properties. However, the bioinert nature of PEEK limits its clinical utility. Developing high-resolution, size-dependent topographies on PEEK surfaces that can precisely control cell behavior remains a significant challenge, impeding the full potential of topography in biomedical applications. Additionally, the interplay between topographical and biochemical cues complicates our understanding of how topography influences cell behavior. In this study, we introduce an innovative method that combines inductively coupled plasma (ICP) with direct stamp imprinting (DSI) to create hierarchical micro/nanotopographies on PEEK surfaces. This approach effectively modulates the morphologies of preosteoblasts and human umbilical vein endothelial cells (HUVECs), resulting in highly organized cellular structures on these micropatterns. Our in vitro and in vivo results demonstrate that hierarchical micro/nanotopography enhances cell orientation, tube formation, preosteoblast osteogenic differentiation, and osseointegration compared to traditional micropatterns. The underlying mechanotransduction mechanism involves the activation of the Yes-associated protein (YAP) signaling pathway, which fosters bone formation. This study underscores the critical role of physical micro/nanotopography in governing cell behavior, mechanotransduction, and functionality. Our findings present a viable strategy for improving angiogenesis and osseointegration of PEEK implants by integrating hierarchical micro/nanotopography. This advancement not only elucidates the mechanisms of cell–substrate interactions but also enhances the potential of PEEK for orthopedic and dental applications.