Thin and soft hydrogel-coated intracortical probe: microfabrication and in vivo biointegration

Intracortical probes are a type of neural interface which can be implanted in the cerebral cortex and offer a high-resolution approach to the stimulation and recording of neural activity. Despite the diagnostic and therapeutic potential of these devices, their clinical applications remain limited due to their performance degradation over time. Recently, a number of studies have been conducted to better understand the mechanisms behind neural implant failure. The onset of an adverse foreign body reaction at the implant-tissue interface is generally associated with the mechanical mismatch between stiff and static devices and soft and dynamic brain tissue. It has been suggested that implanting probes with a minimized cross-section or fabricated with soft, compliant materials can significantly limit neuroinflammation and scarring both over the short and long term. In this work, these two strategies are combined to fabricate a thin and soft intracortical probe. The proposed device consists of a 10 μm thick flexible polyimide (PI) substrate encapsulated between two layers of poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel (20 μm on each side). The hydrogel was used to provide mechanical support during insertion and to shield neural tissue from the underlying stiff substrate, after implantation. The mechanical behavior of the multilayered structure was analyzed to assess the conformability and adhesion of the chosen materials, as well as their insertion mechanics. Hydrogel-coated probes were fabricated and tested in vivo, and acute tissue response was evaluated. Furthermore, a method was proposed for the development of recording probes, integrating the hydrogel in a standard microfabrication process. Experiments confirmed a durable integration of polyimide and the hydrogel, which could generate a stiff system to promote insertion and, simultaneously, exhibit a conformability comparable to that of elastomeric materials. Histology results showed minimal tissue damage after 7 days, compared to stiff substrates. Finally, optimization of microfabrication processes, carried out in a dry state to preserve the integrity of the hydrogel, ultimately led to the development of active probes, which have the potential to detect neural activity. Overall, the obtained results suggest, in a preliminary manner, that it is feasible to develop a hydrogel-coated polyimide probe, which could improve implant biocompatibility, and to incorporate metal electrodes in the proposed thin, soft and flexible system, to provide stable neural sensing and stimulation.