Inflammatory and Regenerative Signalling in Traditional Chinese Medicine Debridement-Granulation Therapy for Chronic Wounds: A Narrative Review.

Chronic non‑healing wounds bring substantial clinical and socioeconomic burdens worldwide. Traditional Chinese medicine (TCM) debridement‑granulation therapy (original therapeutic principle: Qufu Shengji, defined as removing necrotic tissue to stimulate granulation growth) represents a classic topical therapeutic concept for refractory cutaneous ulcers. As a narrative review rather than a pre‑registered systematic review, this work qualitatively integrates publicly available pre‑clinical experimental findings from isolated herbal monomers, compound formulas and topical preparations guided by debridement‑granulation principles. We elaborate their stage‑specific regulatory effects on core signaling cascades corresponding to debridement‑stage and granulation‑formation‑stage processes. It should be noted that almost all mechanistic observations are derived from pre‑clinical cell and animal experiments, and further clinical validation based on human wound samples is urgently required. During the debridement stage, TCM‑derived agents suppress persistent inflammatory cascades by inhibiting NF‑κB, JAK2/STAT3, AGEs‑RAGE and NLRP3/Caspase‑1/Gasdermin‑D pathways, facilitating necrotic tissue clearance and M1‑to‑M2 macrophage phenotypic transformation. During the granulation‑promoting stage, such herbal preparations activate PI3K/Akt, Nrf2/ARE, Wnt/β‑catenin and cAMP/PKA signaling pathways to promote fibroblast proliferation, angiogenesis, collagen deposition and epidermal re‑epithelialization. This review further objectively analyses major limitations within existing pre‑clinical research, including oversimplified animal models, unclear pharmacodynamic material basis of compound prescriptions, insufficient exploration of signaling‑pathway crosstalk, heterogeneous experimental protocols, publication bias and limited safety data for topical TCM preparations. Targeted directions for subsequent mechanistic exploration, novel transdermal‑preparation development and translational clinical verification are proposed. This two‑stage conceptual framework aims to provide theoretical references for future mechanistic and translational studies for TCM wound care, rather than confirming definite clinical therapeutic efficacy.