Abstract
Biodegradable self-healing hydrogels are attractive materials for tissue repair; however, the impact of the self-healing abilities of hydrogels on tissue repair is not clear. In this study, we prepared novel chitosan–cellulose nanofiber (CS–CNF) composite self-healing hydrogels with the same modulus (approximately 2 kPa) but tunable self-healing properties. By adding a low amount of CNFs (0.06–0.15 wt%) in the pristine chitosan (CS) self-healing hydrogel, the reversible dynamic Schiff bonding, strain sensitivity, and self-healing of the hydrogel are obviously affected. Neural stem cells embedded in the CS–CNF hydrogel with better self-healing properties reveal significantly enhanced oxygen metabolism as well as neural differentiation. The differentiation of neural stem cells is highly correlated with their metabolic change in the self-healing hydrogel. Moreover, the neural regeneration effect of the optimized CS–CNF hydrogel with 0.09 wt% CNFs and the best self-healing properties show a 50% improvement over the pristine CS hydrogel in the zebrafish brain injury model. A mechanism is proposed to interpret the tunable self-healing properties of CS–CNF hydrogels with stiffness maintained in a similar range. The new self-healing hydrogels help to clarify the role of self-healing in the biological performance of hydrogels as well as provide design rationale for hydrogels with better injectability and tissue regeneration potential.
Highlights
Hydrogel possesses the capability of holding a large amount of water in a three-dimensional (3D) network and is an attractive class of materials for biomedical applications[1,2]
The surface of 160 μm-needle-injected hydrogels was smooth for the composite hydrogels, for CS–CNF2 and CS–CNF3 hydrogels (Fig. 1B)
The rheological properties of the other chitosan–cellulose nanofiber (CS–Cellulose nanofibers (CNFs)) nanocomposite hydrogels are shown in Fig. S2 (Supplementary data)
Summary
Hydrogel possesses the capability of holding a large amount of water in a three-dimensional (3D) network and is an attractive class of materials for biomedical applications[1,2]. Hydrogels with self-healing properties provide appealing features such as the less short invasive delivery procedure by injection at the target site without gel fragmentation[3]. Self-healing hydrogels with strong tissue adhesion significantly promote wound healing[4,5]. They may carry therapeutic agents to the damaged tissue area, offering a local treatment effect. The self-healing hydrogels may provide an extracellular matrix-like 3D environment for embedded cells and hold promises for tissue engineering applications[6,7,8]
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