Stimulus-Responsive Double Network Hydrogels with MoS₂ Nanosheets for High Toughness and Self-Healing Smart Biomaterials for Tissue Engineering

The design of stimulus-responsive smart hydrogel actuators for tissue engineering holds great promise, as they enable the creation of 3D structures mimicking the functionality of natural tissues, responding in a controlled manner to changes in temperature, light, or pH. To achieve near-infrared (NIR) light-induced responses in smart hydrogels, molybdenum disulfide (MoS₂) nanosheets have gained recent attention due to their layered structures and strong NIR absorbance, making them promising photothermal agents. Among various hydrogels, we focus on double-network hydrogels (DN) composed of chitosan (C) and polyvinyl alcohol (P), known for providing a robust and flexible matrix for cell growth and tissue regeneration. In this study, we developed C-P DN hydrogels with MoS₂ nanoparticles to create 3D printed scaffolds (3D C-P) and evaluated their mechanical properties, water content, NIR light irradiation response, and cell viability.<br/>By adjusting manufacturing parameters like freezing temperature, chitosan cross-linking time, and lyophilization, we tailored the mechanical properties of C-P DN hydrogels. These inks were successfully extruded using a fourth-generation 3D BioplotterTM (Envisiontec, Germany), enabling precise scaffold production. After 2 hours of crosslinking, the 3D C-P scaffold exhibited high toughness and mechanical stiffness resembling native heart tissue, with a stiffness value of 0.78 MPa. Interestingly, DN C-P_MoS₂ hydrogels with 0.5% w/w MoS₂ incorporation did not show improved mechanical stiffness compared to pure DN, maintaining material structural stability. Furthermore, MoS₂ incorporation led to a slight decrease in water content, attributed to its hydrophobic nature.<br/>The material's responsiveness was evident through rapid contraction and bending upon NIR light irradiation due to dehydration, and this response was 40% faster than that of DN C-P hydrogels. This confirmed their potential as candidates for generating light-stimulated smart DN hydrogels. Additionally, MoS₂-incorporated hydrogels exhibited mechanical self-healing under NIR light exposure, enhancing their tissue engineering applications. These multifunctional behaviors arise from MoS₂'s ability to convert light energy into thermal energy, triggering NIR light-induced contraction. Furthermore, NIR-induced heat facilitates polymer chain diffusion, enabling a self-healing process through hydrogen bond reformation in MoS₂-incorporated hydrogels. MoS₂ absorbs NIR light, releasing heat, and leading to hydrogel contraction, while reconstituted hydrogen bonds allow the material to 'heal,' restoring structural integrity and functionality.<br/>Viability studies on umbilical cord-derived mesenchymal stem cells (UC-MSCs) cultured on MoS₂ hydrogels showed improvement from day 1 to day 7, suggesting that DN and DN C-P MoS₂ hydrogels offer a conducive environment for UC-MSC growth and survival, serving as a three-dimensional support and suitable substrate matrix.<br/>The results demonstrate that the incorporation of MoS₂ nanosheets into C-P DN hydrogels achieves a rapid actuation response to NIR light irradiation and a mechanical self-healing behavior, making them ideal for light-stimulated flexible hydrogels. Additionally, cell viability studies indicate MoS₂-containing hydrogels' suitability as three-dimensional support in regenerative medicine and tissue engineering.