Traditional Chinese medicinal strategies for enhanced wound healing: Mechanistic insights and translational advancements

Introduction: Chronic skin wounds, including burns, diabetic foot ulcers, venous leg ulcers, and pressure injuries, represent a growing global healthcare burden due to increasing rates of diabetes, aging populations, and antibiotic resistance. These wounds arise from dysregulated repair processes characterized by persistent inflammation, microbial biofilm formation, oxidative stress, impaired angiogenesis, and defective extracellular matrix remodeling, which collectively limit the effectiveness of current therapies. Despite advances in wound care, existing treatments often fail to address the multifactorial nature of chronic wounds. Traditional Chinese Medicine (TCM) offers a pharmacologically rich source of defined bioactive compounds capable of targeting multiple molecular mechanisms across sequential healing phases, providing a timely and promising strategy for integration with advanced wound-healing technologies. Methods: A comprehensive literature survey was conducted using PubMed, Web of Science, and Scopus to identify peer-reviewed studies on TCM-derived principal compounds and TCM-based formulations for wound healing. Search terms included combinations of keywords related to TCM, cutaneous wound models, nanotechnology, and biomaterials. Eligible studies were screened based on predefined inclusion criteria emphasizing cutaneous relevance, mechanistic insight, and formulation-enhanced bioavailability. Selected studies were organized according to phase-specific wound-healing mechanisms and delivery strategies. Results: TCM principal compounds, including triterpenoid saponins, phenolic acids, flavonoids, naphthoquinones, and polysaccharides, exert complementary effects on key wound-healing pathways. When incorporated into nano- and biomaterial-based platforms such as electrospun nanofibers, hydrogels, nanoemulsions, metal-oxide nanoparticles, microneedle arrays, and metal–organic frameworks, these compounds demonstrate improved stability, dermal penetration, sustained local retention, and controlled release. Mechanistically, nano-enabled TCM systems mediate (i) suppression of infection and inflammation via antimicrobial activity and downregulation of TNF-α and IL-1β; (ii) attenuation of oxidative stress through reactive oxygen species scavenging; (iii) stimulation of angiogenesis and microcirculation via VEGF, bFGF, TGF-β, Akt, ERK, and eNOS pathways; and (iv) promotion of fibroblast proliferation, collagen deposition, ECM remodeling, and re-epithelialization. Discussion: TCM-based nano-enabled and biomaterial-assisted strategies represent multifunctional, stage-responsive wound therapies that integrate traditional pharmacological principles with modern regenerative medicine. Despite compelling preclinical evidence, clinical validation remains limited. Therefore, clinical translation requires standardized phytochemical characterization, reproducible formulation strategies, comprehensive pharmacokinetic and toxicity evaluation, and well-designed randomized clinical trials to establish safe, effective, and scalable wound-healing solutions.