Robust 3D-Printable, Injectable, and Adhesive Hydrogels with Stepwise-Triggered Dual Reversible/Irreversible Covalent Linkages for Wound Healing

The development of 3D-printable and injectable biocompatible hydrogels with robust mechanical and adhesive properties useful for biomedical applications remains a great challenge. Herein, stepwise-triggered dual reversible/irreversible covalent linkages are engineered between two functionalized polymers, glycidyl methacrylate-modified polyvinyl alcohol (PVA-GMA) and oxidized sodium alginate tailed with 3-aminophenylboronic acid (OSA-PBA), allowing the availability of PVA-GMA/OSA-PBA (PGOP) hydrogels with versatile properties and functions. The PGOP hydrogels have excellent injectability, processability, mechanical strength (39.5 ± 2.3 kPa), self-healing, elasticity and toughness (80% compressive strain at 84.5 kPa stress), bioadhesion (34.2 ± 2.7 kPa adhesive strength to fresh pig skin, vs 7.3–15.38 kPa for commercial fibrin glue adhesives), degradability, antibacterial property, and biocompatibility (265% cell survival with fibroblasts co-culture for 5 d). With these merits, PGOP pregel and hydrogels can be applied as 3D-printing glue and construct materials to produce diverse 3D hierarchical architectures with high shape fidelity, good mechanical properties, and active materials-laden capacity. The mouse liver hemorrhage model and the full-thickness skin defect model demonstrate that PGOP hydrogels have excellent hemostatic ability and accelerated wound healing capacity. Therefore, this work provides 3D-printable and injectable glue and hydrogel adhesives with favorable mechanical strength useful for various biomedical applications such as tissue engineering and wound healing.