Bioorthogonally Cross-Linked Injectable PEG Hydrogel with Robust Hemostatic and Antibacterial Properties

The rapid hemostasis of deep and irregular wounds is of great clinical significance. In this study, an injectable hemostatic hydrogel based on bioorthogonal conjugation was developed. This gel uses thrombin (TMB) as the hemostatic active substance and 4ARM-PEG-N₃ as the crosslinking agent, which undergo orthogonal conjugation via the classic azide-alkyne click reaction to form an injectable hydrogel (TMB-PEG). The resulting hydrogel exhibited a transparent, injectable gel state. TEM images revealed that the hydrogel comprised sheet-like structures and interwoven fibers with a diameter of approximately 100 nanometers. In a puncture bleeding wound model, hemostasis with the TMB-PEG hydrogel required only 25 s, with a blood loss of 1.9 ± 1.3 mg, both approximately one-sixth of that of the control group. Moreover, the hemostatic performance of the TMB-PEG hydrogel was far superior to that of three other commonly used hemostatic materials. Furthermore, cephalosporin antibiotics were conjugated to the hemostatic gel via orthogonal reactions, endowing it with significant broad-spectrum antibacterial activity, achieving over 99% antibacterial efficacy against both Gram-negative and Gram-positive bacteria.