Harnessing natural compounds and external stimuli for advanced wound healing: A review of combination therapy strategies

Wound healing represents a complex biological process crucial for tissue repair and regeneration, yet chronic wounds present a persistent challenge in clinical practice affecting millions of people worldwide with escalating medical costs. In recent years, there has been a growing interest in exploring novel therapeutic approaches that harness the wound healing effects of natural compounds and external stimuli to enhance wound healing outcomes. This review examines the emerging field of combination therapy, focusing on the integration of biocompatible natural compounds with external stimuli such as magnetic fields, electrical fields, ultrasound, and light therapy. Natural compounds exhibit antimicrobial, anti-inflammatory, and tissue-regenerative properties, while external stimuli can modulate cellular processes, improve circulation, direct cell migration, and promote tissue regeneration. Stimuli-responsive natural compounds that exhibit complementary mechanisms of action to accelerate wound closure, minimize scar formation, and mitigate the risk of infection are described herein. Ultimately, the integration of natural compounds and external stimuli holds immense promise for wound care and drug release strategies and improving patient outcomes in the management of chronic wounds.