Ana Carolina Monteiro

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.

Acute myeloid leukaemia (AML) management remains a significant challenge in oncology due to its low survival rates and high post-treatment relapse rates, mainly attributed to treatment-resistant leukaemic stem cells (LSCs) residing in bone marrow (BM) niches. This review offers an in-depth analysis of AML progression, highlighting the pivotal role of extracellular vesicles (EVs) in the dynamic remodelling of BM niche intercellular communication. We explore recent advancements elucidating the mechanisms through which EVs facilitate complex crosstalk, effectively promoting AML hallmarks and drug resistance. Adopting a temporal view, we chart the evolving landscape of EV-mediated interactions within the AML niche, underscoring the transformative potential of these insights for therapeutic intervention. Furthermore, the review discusses the emerging understanding of endothelial cell subsets’ impact across BM niches in shaping AML disease progression, adding another layer of complexity to the disease progression and treatment resistance. We highlight the potential of cutting-edge methodologies, such as organ-on-chip (OoC) and single-EV analysis technologies, to provide unprecedented insights into AML–niche interactions in a human setting. Leveraging accumulated insights into AML EV signalling to reconfigure BM niches and pioneer novel approaches to decipher the EV signalling networks that fuel AML within the human context could revolutionise the development of niche-targeted therapy for leukaemia eradication.