Green Gas-Mediated Cross-Linking Generates Biomolecular Hydrogels with Enhanced Strength and Excellent Hemostasis for Wound Healing

Forming biomolecular hydrogels with a combination of high strength and biocompatibility is still a challenge. Herein, we demonstrated a green gas (CO₂)-mediated chemical cross-linking strategy that can produce a double-network cellulose/silk fibroin hydrogel (CSH) with significantly elevated mechanical strength while bypassing the toxicity of routine cross-linking agents. Specifically, cellulose and silk fibroin (SF) were first covalently cross-linked in NaOH/urea solution to create the primary network. Then, CO₂ gas was introduced into the resultant CSH precursor gels to form carbonates to reduce the pH value of the intra-hydrogel environment from basic to neutral conditions. The pH reduction induced the ordered aggregation of cellulose chains and concomitant hydrogen bonding between these chains, leading to the formation of hydrogels with significantly improved mechanical strength. The CSHs could promote the adhesion and proliferation of the mouse fibroblast cell line (L929), and the CSHs proved to be of low hemolysis and could accelerate blood clotting and decrease blood loss. The CSHs with SF content of 1 wt % healed the wound in vivo within only 12 days through the acceleration of re-epithelialization and revascularization. Consequently, our current work not only reported a feasible alternative for wound dressings but also provided a new green gas-mediated cross-linking strategy for generating mechanically strong, hemostatic, and biocompatible hydrogels.