Bio-inspired Lotus-fiber and Mussel-based Multifunctional Hydrogels for Wound Healing: Super-stretchability, Self-healing, Adhesion and Antibacterial Properties

Abstract Hydrogel-based wound dressings, which facilitate rapid wound closure and healing, are essential for effective wound management. However, the development of an ideal hydrogel that possesses excellent mechanical properties, effective self-healing capabilities, tissue adherence and antimicrobial characteristics for wound dressing presents a significant challenge in clinical settings. Inspired by lotus-fiber and mussel, we synthesized a novel multifunctional hydrogel composed of bacterial cellulose-reinforced dopamine-grafted oxidized hyaluronic acid/polyacrylamide (OHA-DA/PAM/BC). This was achieved through a one-pot reaction that employed free radical polymerization of acrylamide, dynamic Schiff bonding and intermolecular hydrogen bonding. Compared with the pure PAM hydrogels, which exhibited an elongation at break of 4022% and a maximum tensile strength of 26.42 kPa, the OHA-DA/PAM hydrogel demonstrated significantly enhanced stretchability at 9949% and an increased tensile strength of 34.73 kPa when 0.3% OHA-DA was incorporated during hydrogel formulation. Notably, the addition of 0.8% BC significantly enhanced the tensile strength to 57.04 kPa and super-stretchability to 10679%. The OHA-DA/PAM/BC hydrogel also exhibited remarkable self-healing capabilities, achieving a mechanical recovery of 84.74% within 12 hours. Additionally, its adhesive and injectable properties are advantageous for dynamic wound repair. Furthermore, the OHA-DA/PAM/BC hydrogel exhibited minimal hemolytic activity and potent intrinsic antibacterial properties against both E. coli and S. aureus. In a mouse model of wound healing, this hydrogel reduced the healing duration to 14 days while enhancing the regeneration of both skin structure and function. Histological analyses further revealed that the hydrogel significantly promoted the development of well-organized granulation tissue, angiogenic tissue and collagen accumulation in the wound region. This study successfully developed an OHA-DA/PAM/BC multifunctional hydrogel characterized by exceptional stretchability, self-healing, adhesiveness, injectability and antibacterial activity, demonstrating a significant impact on wound healing in vivo. These findings indicated that the OHA-DA/PAM/BC hydrogel holds substantial potential as wound dressings for future clinical applications.