Starfish-Inspired Synergistic Reinforced Hydrogel Wound Dressing: Dual Responsiveness and Enhanced Bioactive Compound Delivery for Advanced Skin Regeneration and Management

Effective wound management demands advanced dressings that protect while actively supporting healing. Traditional wound dressings often fall short of meeting the complex needs of skin repair. Inspired by the regenerative abilities of starfish, we developed a bionically engineered hydrogel designed to enhance wound healing. The hydrogel is synthesized through the coassembly of dopamine-modified cellulose nanofibers, chitosan, (3-aminobenzeneboronic acid)-grafted oxidized dextran, and poly(vinyl alcohol), utilizing dynamic Schiff base and boronic ester linkages. This innovative design imparts multifunctional properties, including injectability, 3D printability, antibacterial activity, self-adhesion, self-healing, antioxidant protection, and hemostasis, which emulate the defense mechanisms and regenerative processes of starfish. These characteristics work synergistically to reduce infection and oxidative stress and improve healing efficiency. Additionally, the hydrogel incorporates mangiferin and Vitamin C, which are released in a controlled manner in response to the wound's microenvironment (pH and reactive oxygen species), promoting tissue regeneration and reducing inflammation. <i>In vitro</i> tests confirmed its dual responsiveness, while finite element modeling validated the controlled release of bioactive compounds. <i>In vivo</i> testing on a rat full-thickness wound model showed a 100% healing rate by day 13, significantly outperforming commercial alternatives. The hydrogel's nontoxicity and advanced healing capabilities make it a promising solution for patients with critical healing needs, offering a comprehensive integration of natural biological processes and cutting-edge engineering.