An Injectable, Electroconductive Hydrogel/Scaffold for Neural Repair and Motion Sensing

Abstract

Electroconductive hydrogels and scaffolds have great potential for strain sensing and in tissue engineering. Herein, we designed electroconductive self-healing hydrogels and shaperecoverable scaffolds with injectability, strain/motion-sensing ability, and neural regeneration capacity. The crosslinked network of hydrogels and scaffolds was synthesized and prepared under physiological conditions from N-carboxyethyl chitosan (CEC), a chitosan-modified polypyrrole (DCP) nanoparticle (∼40 nm), and a unique aldehyde-terminated difunctional polyurethane (DFPU) crosslinker. CEC was mixed with DCP by electrostatic interaction and then crosslinked with DFPU through a dynamic Schiff base reaction. Schiff base endowed the hydrogels with self-healing behavior, confirmed by rheological examinations. Shape-recoverable scaffolds were obtained by freeze-drying the hydrogels. These hydrogels and scaffolds showed injectability and conductivity (3− 6 mS/cm), while the scaffolds also exhibited high water absorption and durable elasticity after repeated deformation. The hydrogels and scaffolds promoted the attachment, proliferation, and differentiation of neural stem cells (NSCs). The scaffolds had excellent strain/motion-sensing properties in vitro and ex vivo as well as biodegradability and biocompatibility in vivo. Moreover, the neural regeneration capacity of the conductive hydrogel or the cell-laden conductive hydrogel was demonstrated by the rescue of motor function (∼53 and ∼80% functional recoveries, respectively) in the zebrafish brain injury model. These hydrogels and scaffolds are potential candidates for nerve repair and motion sensing.

Thermoresponsive and Conductive Chitosan-Polyurethane Biocompatible Thin Films with Potential Coating Application

“…The synthesis of nanoparticle DCP was based on the previous literature [28,30]. Chitosan was modified with MAA to produce double bond chitosan (DCS) as an intermediate.…”

“…Recently, a hydrated conductive hydrogel/scaffold with three-dimensional porous structure and needle injectability was developed [28]. Conductive nanoparticles (i.e., double-bonded chitosan grafted polypyrrole, DCP) used in the earlier work showed good biocompatibility and considerable conductivity.…”

“…However, such a hydrogel/scaffold can only be used under a hydrated state to present various properties. Most chitosanbased hydrogels, including the one published earlier [28], are brittle after drying, while conductive films need to keep favorable physical properties and biocompatibility in the dried state. Therefore, this is a new attempt to develop a biodegradable conductive film with low brittleness and coating possibility.…”

Multifunctional and Self-Healable Intelligent Hydrogels for Cancer Drug Delivery and Promoting Tissue Regeneration In Vivo

“…Hydrogels improve cell survival via carrying stem cells, especially self-healing hydrogels with high stability in situ gelations. Electroconductive self-healing hydrogels could regulate migration, differentiation, metabolism, adhesion and, a proliferation of electrically excitable cells, which is critical for neural tissue engineering [ 90 ]. For example, nanocomposite self-healing hydrogel from N -carboxyethyl chitosan (CEC) with polypyrrole (DCP) nanoparticle (~40 nm) and a unique aldehyde-terminated difunctional polyurethane (DFPU) as linker revealed electroconductive properties in vitro and in vivo.…”

“…For example, nanocomposite self-healing hydrogel from N -carboxyethyl chitosan (CEC) with polypyrrole (DCP) nanoparticle (~40 nm) and a unique aldehyde-terminated difunctional polyurethane (DFPU) as linker revealed electroconductive properties in vitro and in vivo. This hydrogel could stimulate proliferation, attachment, and differentiation of neural stem cells (NSCs) [ 90 ]. Recently, semi-interpenetrating polymer network (SIPN) hydrogels have been studied for cell encapsulation consisting of linear, branched, and crosslinked polymeric networks [ 91 ].…”