Oxidized Pectin-Amine-Modified Chitosan/PEDOT with Decellularized Human Spinal Cord-Based Self-Healing and Electroconductive Hydrogel for Potential Spinal Regeneration Applications

Abstract

Decellularized extracellular matrix (dECM)-based biomaterials have emerged as promising therapeutic platforms for spinal cord injury (SCI) repair due to their ability to provide regenerative biochemical cues. In this study, we developed an injectable, electroconductive, and self-healing hydrogel for potential application in SCI repair. Injectability enables minimally invasive delivery, electroconductivity facilitates electrical communication that may promote neural regeneration, and self-healing properties allow restoration of the hydrogel network following shear stress during injection. The self-healing hydrogel was formulated using Schiff-base chemistry between aldehyde-functionalized pectin (PEC-ALD) and amine-functionalized chitosan (CS). Poly(3,4-ethylenedioxythiophene) (PEDOT) derivatives were incorporated to enhance electrical conductivity and support neuronal differentiation and axonal outgrowth. In addition, decellularized human spinal cord (dSC), prepared using a modified Hudson protocol, was incorporated to provide tissue-specific pro-regenerative cues. The resulting PEC-ALD-CS-PEDOT-dSC hydrogels exhibited dynamic self-healing behavior characteristic of native spinal cord tissue. Under high oscillatory strain (1000%), the hydrogel network structure temporarily dissociated, while recovery of the crosslinked network occurred upon reduction to low strain (1%). The hydrogels demonstrated a storage modulus of approximately 600 Pa, consistent with the mechanical properties favorable for neuronal growth. Incorporation of PEDOT derivatives resulted in an electrical conductivity of approximately 5.6 mS/cm. Schiff base-mediated crosslinking enabled rapid gelation within 20 min at 37 °C. Furthermore, the hydrogels exhibited shear-thinning behavior, supporting their suitability for injectable delivery. Biological evaluation demonstrated immunomodulatory potential, as RAW 264.7 macrophages encapsulated within the hydrogel exhibited greater CD206 expression relative to CD86 expression, even under lipopolysaccharide-induced inflammatory conditions. Additionally, the hydrogels supported proliferation of human SH-SY5Y neuroblastoma cells, indicating cytocompatibility and potential to support neural regeneration. Overall, this study presents a multifunctional self-healing and electroconductive hydrogel platform incorporating decellularized spinal cord matrix for potential minimally invasive treatment of SCI.