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

Abstract 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.