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.

中文翻译：

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基于右旋糖酐-接枝-四苯胺和N-羧乙基壳聚糖的可降解导电自修复水凝胶，作为成肌细胞治疗和肌肉再生的可注射载体。

可注射的导电水凝胶具有巨大的潜力，可作为组织工程支架和输送载体用于电信号敏感的细胞治疗。在这项工作中，我们介绍了一系列具有快速自我修复能力的可注射电活性可降解水凝胶的合成及其作为骨骼肌再生细胞递送载体的潜在应用。在生理条件下合成了基于葡聚糖-苯胺-苯胺四聚物-接枝-4-甲酰基苯甲酸和N-羧乙基壳聚糖的自修复导电性可注射水凝胶。N-羧乙基壳聚糖中甲酰苯甲酸和胺基之间的动态席夫碱键赋予水凝胶快速的自愈能力，流变试验证明了这一点。平衡的溶胀率，形态，机械强度，充分研究了可注射水凝胶的电化学和电导率。可自我修复的导电水凝胶显示出体内可注射性和线性降解性能。通过自愈作用，两种不同类型的细胞（C2C12成肌细胞和人脐静脉内皮细胞（HUVEC））被包裹在水凝胶中。L929成纤维细胞的培养结果表明了水凝胶的生物相容性。此外，C2C12成肌细胞从导电水凝胶中以线性分布释放。体内骨骼肌再生也曾在容积性肌肉丢失损伤模型中进行过研究。所有这些数据表明，这些可生物降解的自修复导电水凝胶是潜在的候选者，可作为骨骼肌修复的细胞递送载体和支架。重要性声明：具有自愈性和导电性的可注射水凝胶是成肌细胞治疗和骨骼肌再生的组织工程支架的极佳候选者。这些水凝胶的自愈特性可以延长其寿命。然而，大多数报道的导电水凝胶是不可降解的或不具有自愈能力。在本文中，我们基于在先前工作中合成的壳聚糖接枝四苯胺水凝胶，合成了抗菌导电自我修复水凝胶作为用于心脏细胞治疗的细胞递送载体。但是，在该研究中，使用酸性溶液溶解了聚合物，这可能会诱导对细胞的毒性。在这项工作中，我们合成了一系列由N-羧乙基壳聚糖（CECS）和右旋糖酐-接枝苯胺低聚物组成的具有快速自愈能力的可注射电活性生物可降解水凝胶，这些水凝胶可溶于pH 7.4的PBS溶液中。我们进一步证明了其作为骨骼肌再生细胞传递载体的潜在应用。