Neuronal Uptake of Nano‐Sized PMMA Orthopedic Wear Particles in a Compartmentalized Microfluidic Model Revealed by Label‐Free Confocal Raman Microscopy

Periprosthetic inflammation is a major cause of implant failure and is frequently associated with persistent pain, yet prevailing models remain largely immune‐centric. Periprosthetic tissues are innervated by sensory nerve fibers, but their interaction with implant‐derived wear particles remains poorly understood. Here, we investigate the interaction of nano‐sized poly(methyl methacrylate) particles (PMMA NPs, 117 nm) with sensory neurons using compartmentalized microfluidic cultures of dissociated dorsal root ganglia (DRG) neurons and intact DRG explants. Following selective axonal exposure, PMMA‐FITC‐associated fluorescence was detected along axons and within NeuN‐positive neuronal somata. Label‐free confocal Raman microscopy further identified PMMA‐specific vibrational signatures within the neuronal model, providing complementary chemical evidence of PMMA‐associated signal. In parallel, exposure of primary human macrophages to PMMA NPs did not induce pro‐ or anti‐inflammatory polarization profile or cytokine activation under the conditions tested. Together, these findings demonstrate that nano‐sized PMMA particles interact with sensory neurons and that PMMA‐associated signal can be detected within neuronal somata following selective axonal exposure. These observations are consistent with PMMA transport from axonal terminals towards the soma and highlight an underexplored aspect of neuron–particle interactions in the periprosthetic environment. Label‐free confocal Raman microscopy provides a complementary approach for chemical identification of PMMA within neuronal models.