Development of minimally invasive neuromodulatory electroconductive hydrogel in combination with physical stimuli for spinal cord regeneration

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This MSCA project aims to address the debilitating impact of spinal cord injury (SCI), a condition that currently has no cure. Our goal is to develop a minimally invasive, combinational approach to spinal cord regeneration (SCR) that combines regenerative methods with rehabilitation techniques to enhance functional outcomes. Specifically, we integrate rehabilitation strategies using electrical stimulation (ES) and near-infrared (NIR) laser stimulation to maximize the effectiveness of regeneration. To achieve this, we have designed a multifunctional silk-based electroconductive hydrogel (ECH) that self-assembles without the need for chemical cross-linkers, using the hydrophobic amino acid sequences found in silk fibroin. Our project leverages naturally derived silks, including Bombyx mori (mulberry silk) and Antheraea assamensis (Indian non-mulberry silk), to create these minimally invasive hydrogels. We further enhance their functionality by incorporating PEDOT:PSS, a polymer with mixed ionic and electronic conductivity, to align with the ionic properties of biological tissues. A key focus of our research is to study the electrochemical behavior of these ECHs, optimizing parameters such as charge-transfer resistance and charge injection capacity. Our aim is to fine-tune their electrochemical and electronic properties for efficient and safe electrical stimulation of human induced pluripotent stem cells (hiPSC) derived neuronal systems at low potentials. We are also investigating the fundamental gelation mechanisms of silk combined with conductive polymers, with particular emphasis on adjusting their rheological properties to explore their potential use as bioinks. In addition to neuromodulation, we study how the combined bioactivity of the minimally invasive hydrogel, electrical stimulation, and light stimulation can modulate the immune response of human blood-derived macrophages, contributing to a comprehensive regenerative strategy for SCI patients.