Light-responsible ECM-mimetic scaffolds for neural differentiation. Intracellular versus extracellular photothermal stimulation

The development of approaches and materials that combine several types of stimulatory effects on nerve tissue growth is a promising task for biotechnology. The aim of this work was a comparative study of the influence of intracellularly and extracellularly localized polydopamine-containing materials on the heat-mediated facilitation of neuronal differentiation. Scaffolds made from aligned nylon nanofibers, mimicking the structure of the extracellular matrix, were used as a matrix for immobilizing photothermal nanoparticles. The composite material combines an ultrastructure capable of accelerating and directing the growth of nerve extensions and the ability for controlled thermal remote influence on cell activity under NIR irradiation within the biological transparency range. The materials demonstrated high photostability and biocompatibility without the drawbacks associated with intracellular nanoparticle delivery, such as cytotoxicity and gradual elimination from the body. The immobilization of thermoplasmonic elements on the fibers surface allows for more controlled and manageable heating compared to intracellular introduction of PDA nanoparticles. The fibrous material's ultrastructure directs neurite growth and enhances elongation. Photothermal stimulation further enhances this process by increasing the proportion of cells with longer neurites, thus enhancing neuronal differentiation. Composite nanomaterials can be used for neuromodulation, managing the functional activity of cells, particularly where directed growth is needed, such as in the regeneration of peripheral nerve tissue. This work brings us closer to the creation of smart materials that are biocompatible and easy to manufacture for developing scalable thermal stimulation techniques in regenerative medicine. • Nylon photothermal nanofibers coated with polydopamine have been engineered. • The composite nanomaterial has high photostability and biocompatibility. • Immobilizing PDA nanoparticles on fiber surfaces enables more controlled heating than intracellular delivery. • Composite material enables NIR - induced intracellular temperature changes up to 20 ​°C. • Biomimetic architecture and photothermal stimulation synergistically enhances neuronal differentiation.