Synergistic Wound Healing: Unraveling the Multi-Target Effects of Traditional Chinese Medicine and Its Biomaterials on Chronic Wound Pathways

Chronic wounds, including diabetic ulcers (DUs), radiation-induced ulcers, and burns, present significant clinical challenges due to their distinct pathological mechanisms, necessitating tailored therapeutic strategies. Diabetic ulcers, characterized by impaired angiogenesis, persistent inflammation, and hyperglycemia, require dual modulation of inflammatory (NF-κB) and pro-repair (PI3K/Akt, Nrf2) pathways. Radiation ulcers involve DNA damage, NLRP3-driven inflammation, and TGF-β/Smad-mediated fibrosis, while burns trigger acute inflammation via DAMPs/PAMPs-TLR/NLR activation. Traditional Chinese medicine (TCM) and its bioactive components, such as Scutellaria baicalensis, curcumin, and Panax notoginseng, exhibit multi-target therapeutic effects by regulating oxidative stress, inflammation, angiogenesis, and extracellular matrix remodeling through key pathways, including Nrf2/ARE, MAPK, NF-κB, PI3K/Akt, HIF-1α/VEGF, Wnt/β-catenin, and TGF-β/Smad. Emerging supramolecular self-assembled biomaterials-nanofibrous scaffolds, hydrogels, and microneedles-address the hydrophobicity and low bioavailability of natural plant-derived macromolecules (NPHMs), enabling spatiotemporally controlled drug delivery. Innovative formulations, such as curcumin-loaded hydrogels and exosome-based systems, enhance antioxidant, anti-inflammatory, and pro-angiogenic activities, accelerating wound closure. Despite progress, challenges remain in optimizing multifunctional co-assembly systems, elucidating NPHM self-assembly mechanisms, and developing smart biomaterials responsive to dynamic wound microenvironments. Future research should focus on clinical translation by improving material stability, refining stimulus-responsive release systems, and integrating interdisciplinary insights from herbal medicine, nanotechnology, and regenerative biology. This review systematically summarizes the mechanistic roles of TCM in wound healing, highlights advancements in bioactive material design, and outlines future directions to bridge traditional knowledge with modern therapeutic innovations, offering a scientific foundation for advancing chronic wound management.