Entanglement-Driven Adhesion, Self-Healing, and High Stretchability of Double-Network PEG-Based Hydrogels

Hydrogels that are capable of wet adhesion and self-healing can enable major advances in a variety of biomedical applications such as tissue regeneration, wound dressings, wearable/implantable devices, and drug delivery. We hereby developed an innovative but simple strategy to achieve adhesive, self-healing, and highly stretchable double-network hydrogels, which were composed of a primary covalent polyethylene glycol diacrylate (PEGDA) network in combination with a noncovalent network of highly diffusive, giant PEG chains. The adhesion to substrates including tissue matrices was instant and repeatable due to the diffusive PEG chains that can spontaneously penetrate and entangle with the substrate network. Combining the intrinsic biocompatibility of PEG and rational design for tuning the hydrogel network properties, we exemplarily demonstrated that this hydrogel can be used as a three-dimensional matrix for cell culture or as a tissue adhesive for wound healing. The in vivo study showed that the hydrogel is capable of effectively triggering skin wound healing with a significantly lower immune response in comparison to commercial tissue adhesives currently used in clinics. Therefore, our study provides new and critical insights into the design strategy to achieve adhesion and rehealability by taking advantages of the entanglement effect from double-network hydrogels and opens up a new avenue for the application of entanglement-driven hydrogels in regenerative medicine.