Functional Disorder at the Neural Interface: How Disordered Nanostructures Promote Proper Growth and Differentiation in In Vitro Neural Cultures

The performance and reliability of neural interfaces critically depend on the ability to engineer electrode-tissue interactions across multiple length scales. In this review, we introduce functional disorder as a new unifying design paradigm for manufacturing inorganic nanostructured biointerfaces. We introduce the term functional disorder to denote a non-periodic, spatially heterogeneous, multiscale nanotopography whose irregular geometry is functionally relevant at the cell-electrode interface. We focus on how tailored nanotopography can be exploited to modulate key interfacial properties relevant to in vitro neural platforms, including effective impedance reduction, enhanced electrical coupling, and improved signal recording from both neuronal and glial populations. Beyond electrical performance, functionally disordered nano-architectures provide complex topographical and mechanical cues that influence cell adhesion, morphology, and differentiation, enabling more stable and physiologically relevant interfaces. By critically analysing fabrication strategies and structure-property relationships without restricting the discussion to specific material systems, this review establishes general principles linking disorder, interfacial functionality, and biological response. Overall, we propose functional disorder as a rational and scalable framework to guide the design of next-generation in vitro neural interfaces with improved performance, robustness, and biological integration.