Biomimetic Multifunctional Hydrogels from Jelly Fig Polysaccharide ( <i>Ficus awkeotsang</i> Makino), Alginate, and Genistein for Enhanced Diabetic Wound Healing Applications

The main causes of delayed wound healing in diabetes are bacterial infections, inadequate vasculature, tissue inflammation, and impaired collagen deposition. Here, hydrogels based on jelly fig polysaccharide (JFP) and alginate (Alg) were created using calcium ion crosslinking, which may aid in treating diabetic wounds. Genistein (Gen) was loaded as a bioactive ingredient due to its wound healing, anti-inflammatory, and antioxidant capabilities. The physicochemical characterization of the hydrogels revealed that the hydrogels exhibited significant swelling and biodegradation. The JFP + Alg + Gen 0.05% hydrogel presented significantly greater antioxidant activity (71 ± 3.5%) compared to other hydrogels. The antibacterial studies showed that the JFP + Alg + Gen 0.05% hydrogel exhibited significantly higher inhibition against <i>Staphylococcus aureus</i> (<i>S. aureus</i>). <i>In</i> <i>vitro</i> cell culture studies revealed that the JFP + Alg + Gen hydrogel supported adequate cell viability and proliferation. In addition, <i>in</i> <i>vivo</i> animal experiments were carried out using Wistar albino rats to determine the efficacy of these hydrogels in diabetic wound healing applications. The JFP + Alg + Gen 0.05% hydrogel-treated group displayed faster wound contraction and shorter re-epithelialization time (21 ± 1 days) compared to the control (30 ± 2 days), JFP, and Alg hydrogels (24 ± 2 days). Furthermore, the JFP + Alg + Gen 0.05% hydrogel-treated wounds showed greater vasculature, collagen synthesis, and reduced inflammation compared to the control. Overall, the JFP + Alg + Gen 0.05% hydrogel showed 30% more therapeutic potential against diabetic wounds than the control.