Speaker
Description
Implantable peripheral neural interfaces (PNIs) have demonstrated considerable versatility by facilitating direct access to targeted nerves with high signal specificity, thereby enabling both the acquisition of physiological information through electrical recording and the modulation of organ function via controlled electrical stimulation. However, the long-term performance of most implantable devices remains suboptimal due to persistent mechanical and procedural challenges. A primary cause of tissue damage arises from the modulus mismatch between the compliant neural tissue and the rigid conventional electrode materials. Moreover, in practical settings, the epineurium is often excised to improve the signal-to-noise ratio, a procedure that further exacerbates mechanical trauma and incites inflammatory responses, resulting in tissue encapsulation. Collectively, these adverse biological reactions—ranging from physical damage to fibrotic tissue formation—diminish electrical signal transmission and ultimately compromise the chronic stability and functional integrity of PNIs. To overcome these limitations, we propose a neural tissue-specific adhesive hydrogel engineered to support peripheral nerve regeneration and preserve sustained neural signal fidelity at the interface. We developed neural protein-enriched extracellular matrix adhesives (NeuPEA) by incorporating recombinant Annexin A2, which is a pivotal protein in peripheral nerve repair, into ECM hydrogels enriched with proteins associated with peripheral neural tissue. Schwann cells cultured within NeuPEA exhibited markedly upregulated neural-specific gene expression and enhanced functional activity compared to those within non-nerve-specific ECMs, validating its superior bioactivity and regenerative potential. To impart tissue adhesiveness, tyrosine residues were chemically converted into L-3,4-dihydroxyphenylalanine (L-DOPA), a natural catechol-based adhesive moiety. This transformation was achieved via visible light-induced oxidation using a ruthenium/sodium persulfate photocrosslinking system, facilitating rapid and robust hydrogel adhesion to both neural tissues and electrode substrates. Notably, the L-DOPA content increased quantitatively in direct proportion to the NeuPEA concentration. Additionally, NeuPEA exhibited a lower modulus compared to native nerve tissue, offering improved compliance and thereby alleviating modulus mismatch-induced tissue injury. This mechanical softness further contributed to reduced viscosity and lower injection force, enabling easy administration within confined peripheral nerve regions. Importantly, the hydrogel maintained high electrical conductivity and low impedance, both of which are essential for the reliable acquisition of neural signals without interference. Finally, we successfully stimulated the rat sciatic nerve, as evidenced by ankle movement, and acquired sensory signals in response to various stimuli such as brushing and pressing. Overall, NeuPEA represents a promising neural adhesive hydrogel that combines regenerative capability with multifunctional properties, offering integrated material strategies for enhanced long-term stability and performance of PNIs, with potential applications in neural interface engineering and regenerative bioelectronic systems.
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