Degradable conductive self-healing hydrogels based on dextran-graft-tetraaniline and N-carboxyethyl chitosan as injectable carriers for myoblast cell therapy and muscle regeneration

Abstract

Injectable conductive hydrogels have great potential as tissue engineering scaffolds and delivery vehicles for electrical signal sensitive cell therapy. In this work, we present the synthesis of a series of injectable electroactive degradable hydrogels with rapid self-healing ability and their potential application as cell delivery vehicles for skeletal muscle regeneration. Self-healable conductive injectable hydrogels based on dextran-graft-aniline tetramer-graft-4-formylbenzoic acid and N-carboxyethyl chitosan were synthesized at physiological conditions. The dynamic Schiff base bonds between the formylbenzoic acid and amine group from N-carboxyethyl chitosan endowed the hydrogels with rapid self-healing ability, which was verified by rheological test. Equilibrated swelling ratio, morphology, mechanical strength, electrochemistry and conductivity of the injectable hydrogels were fully investigated. The self-healable conductive hydrogels showed an in vivo injectability and a linear-like degradation behavior. Two different kinds of cells (C2C12 myoblasts and human umbilical vein endothelial cells (HUVEC)) were encapsulated in the hydrogels by self-healing effect. The L929 fibroblast cell culture results indicated the biocompatibility of the hydrogels. Moreover, the C2C12 myoblast cells were released from the conductive hydrogels with a linear-like profile. The in vivo skeletal muscle regeneration was also studied in a volumetric muscle loss injury model. All these data indicated that these biodegradable self-healing conductive hydrogels are potential candidates as cell delivery vehicles and scaffolds for skeletal muscle repair. STATEMENT OF SIGNIFICANCE: Injectable hydrogels with self-healing and electrical conductivity properties are excellent candidates as tissue-engineered scaffolds for myoblast cell therapy and skeletal muscle regeneration. The self-healing property of these hydrogels can prolong their lifespan. However, most of the reported conductive hydrogels are not degradable or do not have the self-healing ability. Herein, we synthesized antibacterial conductive self-healing hydrogels as a cell delivery carrier for cardiac cell therapy based on chitosan-grafted-tetraaniline hydrogels synthesized in our previous work. However, an acid solution was used to dissolve the polymers in that study, which may induce toxicity to cells. In this work, we synthesized a series of injectable electroactive biodegradable hydrogels with rapid self-healing ability composed of N-carboxyethyl chitosan (CECS) and dextran-graft-aniline oligomers, and these hydrogel precusor can dissolve in PBS solution of pH 7.4; we further demonstrated their potential application as cell delivery vehicles for skeletal muscle regeneration.