Advances in Chinese herbal medicine for diabetic wound treatment: from tradition to innovation

Diabetic wounds represent one of the most intractable complications of diabetes, arising from a highly complex and self-perpetuating pathological microenvironment. This milieu is characterized by chronic inflammation, oxidative stress, impaired angiogenesis, peripheral neuropathy, immune dysregulation, recurrent infection, and marked dysfunction of resident cells and the extracellular matrix (ECM). These intertwined abnormalities not only hinder wound closure but also significantly increase the risk of chronic infection, amputation, and disability, thereby imposing substantial clinical and socioeconomic burdens. Conventional therapies, which typically target isolated aspects of wound pathology, often fail to disrupt the vicious cycle of non-healing, underscoring the urgent need for integrated, multi-target therapeutic strategies. Chinese herbal medicine (CHM) encapsulates a holistic therapeutic paradigm that is intrinsically aligned with the multi-factorial nature of diabetic wound management. CHM offers a diverse array of bioactive ingredients, including polysaccharides, saponins, flavonoids, alkaloids, and phenolics, that collectively exert anti-inflammatory, antioxidant, pro-angiogenic, neuroprotective, immunomodulatory, antimicrobial, and pro-proliferative effects. Moreover, many of these ingredients exhibit pleiotropic effects, enabling concomitant modulation of multiple pathological pathways to address the inherent complexity of diabetic wounds. However, the clinical translation of raw CHM is frequently hindered by poor bioavailability and rapid degradation at the wound site. Recent advances in CHM-based innovative delivery platforms have provided a transformative framework to overcome these limitations. This review highlights the emergence of CHM-loaded hydrogels and CHM-derived plant exosome-like nanovesicles (PELNs) as next-generation interventions. CHM-loaded hydrogels act as biomimetic scaffolds that facilitate controlled release and adaptively respond to microenvironmental cues (e.g., pH and reactive oxygen species (ROS)). Simultaneously, CHM-derived exosome-like nanovesicles serve as natural, biocompatible nanocarriers that enhance cellular uptake and molecular signaling, promoting regenerative healing through intercellular communication pathways. In this review, we systematically summarize the pathological features of diabetic wounds and synthesize the modern pharmacological mechanisms of representative CHM ingredients. We further evaluate the synergistic integration of CHM with advanced biomaterials and nanotechnology, emphasizing their translational potential from preclinical models to clinical evidence. By bridging traditional wisdom with cutting-edge bioengineering, these platforms offer a robust evidence-based framework for the modernized management of diabetic wounds.