Sodium hyaluronate-based hydrogels with enhanced mechanical properties and anti-oxidant and anti-inflammatory characteristics for wound healing

Hyaluronic acid-xanthan gum-NAGA composite hydrogels were made using polyphenols. • Tea polyphenols optimizes mechanical, pH-response, and antioxidant properties. • NHXTP significantly upregulates IL-10 and suppresses IL-1β and TNF-α expression. • NHXTP accelerates wound closure in a rat full-thickness skin defect model. • NHXTP promotes organized tissue regeneration in full-thickness skin defect rats. Functional hydrogel dressings that combine excellent mechanical properties, biological activity, and environmental responsiveness are urgently needed in wound management. Polyphenols have antioxidant, anti-inflammatory, and wound-healing properties. However, their impact on structural fidelity and long-term stability in 3D-printed hydrogel systems remains poorly understood. Additionally, previous studies lack systematic investigation into swelling behavior within the dynamic pH environment of wound healing. This study aims to develop a multifunctional wound dressing capable of adapting to dynamic pH changes within wounds through systematic modification with polyphenols. Functionalized hyaluronic acid (HA)-xanthan gum (XG)-N-acryloylglycine (NAGA) composite hydrogels (NHX) were prepared using a polyphenol (tea polyphenols (TP), tannic acid (TA), and gallic acid (GA) immersion modification strategy. The effects of polyphenol type, concentration, and immersion time on the material properties were systematically investigated. Incorporating TPs synergistically optimized mechanical properties (337% tensile strain, 0.45 MPa stress), pH-responsive swelling behavior (up to 160% swelling at pH 9), and antioxidant activity (ABTS scavenging >99%) of the hydrogel by forming dynamic hydrogen bonds within the polymer network. In vitro anti-inflammatory experiments confirmed that the NHXTP hydrogel significantly upregulates IL-10, and suppresses IL-1β and TNF-α expression. In a rat full-thickness skin defect model, NHXTP dressings markedly accelerated wound closure (98.1% healing rate at 14 days) and promoted organized tissue regeneration. These findings contribute to the development of next-generation high-performance wound dressings.