Recent Advances in Flavonoid-Based Therapeutics for Wound Healing: Focus on Polymeric and Hybrid Delivery Systems

Wound healing is a highly intricate biological process that progresses through sequential phases: haemostasis, inflammation, proliferation, and remodelling, each regulated by a series of cellular and molecular mechanisms. The healing process is often impaired by chronic inflammation, oxidative stress, infections, and other pathological conditions, resulting in delayed tissue regeneration. Natural flavonoids, with their antioxidant, anti-inflammatory, antimicrobial, and pro-angiogenic properties, have gained significant attention as potential therapeutic agents for enhancing wound repair. However, their clinical application remains constrained by challenges such as poor water solubility, low bioavailability, rapid metabolism, and instability under physiological conditions. To address these limitations, polymer-based delivery systems-including hydrogels, nanofibers, nanoparticles, and hybrid formulations-have been developed using natural, synthetic, and semi-synthetic polymers. These systems offer improved drug encapsulation, sustained release, targeted delivery, and enhanced stability, thereby optimizing the therapeutic potential of flavonoids in wound management. This review comprehensively discusses the characteristics, selection criteria, and mechanisms of polymer and hybrid systems employed for flavonoid delivery, along with their synergistic effects on tissue regeneration. Furthermore, it provides a translational framework for designing multifunctional wound healing platforms, highlighting the promise of polymeric carriers in overcoming pharmacokinetic barriers and achieving improved clinical outcomes.