Abstract
Effective wound management demands novel therapeutic strategies that overcome the limitations of medication by reducing inflammation, preventing infection, and accelerating tissue regeneration. The present review provides an extensive examination of natural therapeutic agents incorporated into polymeric hydrogels for wound healing purposes. Significant focus has been paid towards extraction techniques that validate the standardization, purity, and biological efficacy of natural compounds, alongside several principal incorporation strategies: direct mixing, in situ incorporation, post-loading, and nano/microencapsulation, aimed at optimizing the stability of bioactive molecules within hydrogel matrices. Representative in vitro and in vivo studies are summarized to highlight the bioactive and therapeutic effects of hybrid systems based on polymeric hydrogels. Collectively, reported evidence indicates that natural-extract-loaded hydrogels accelerate wound healing through multiple complementary mechanisms, including inflammation modulation, antimicrobial protection, moisture balance, and enhanced tissue regeneration. Furthermore, synergistic mixtures of bioactive compounds have demonstrated enhanced antimicrobial and regenerative efficacy compared to single-component formulations. Overall, bioactive hydrogels incorporating standardized or nano-encapsulated natural extracts represent a new generation of multifunctional, non-pharmaceutic wound dressings that provide excellent biocompatibility and enhanced tissue regeneration in both acute and chronic wound healing.