A novel composite hydrogel containing natural polysaccharides derived from Atractylodes macrocephala Koidz. for diabetic wound healing

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic wounds present significant clinical challenges owing to their impaired healing. It is evident that current therapeutic strategies are ineffective, underscoring the need for more efficient approaches. Atractylodes macrocephala Koidz. (AM) has been shown to exhibit hypoglycemic, anti-inflammatory, and antioxidant properties, which make it a potential therapeutic agent for diabetic wounds. However, the bioactive components and efficacy mechanism remain unclear. AIM OF THE STUDY: The purpose of this study is to extract polysaccharides from AM (AMP) and construct AMP-loaded composite hydrogels, characterize their chemical and structural properties, then investigate their efficacy and potential mechanism of action for diabetic wound care. MATERIALS AND METHODS: AMP was extracted and purified from AM via water decoction and the Sevag method. The composition and structure of AMP were characterized using UV-Vis spectroscopy, FT-IR, HPGPC, ion chromatography, and SEM. A high-glucose-induced HUVEC model was established to study the properties of AMP in terms of its pro-proliferative, promigratory, and tubule formation abilities. The effect of AMP on macrophage inflammatory responses was evaluated via qPCR and ELISA. The structural and mechanical characteristics of the AMP-loaded composite hydrogels were investigated by SEM, FT-IR and rheological analysis. Meanwhile, a full-thickness excisional diabetic mouse model was established to investigate the therapeutic effect. Hematoxylin and Eosin staining and other immunohistochemical analyses were further conducted to explore the potential mechanism. RESULTS: AMP was identified as a homogeneous heteropolysaccharide with an average molecular weight of 3454 Da. It promoted the proliferation, migration, and tubule formation of HUVECs in a high-glucose environment. Meanwhile, AMP decreased the inflammatory response of M1-type macrophages induced by LPS and promoted macrophage polarization toward the M2 phenotype. Moreover, the composite hydrogel composed of AMP and CBM940/CMC-Na showed more stable networks, high porosity, good rheological properties, and biocompatibility. Such composite hydrogels significantly accelerated the healing of diabetic wounds by upregulating CD31 expression and reducing TNF-α and NF-κB levels in the wound area. CONCLUSIONS: The AMP and AMP-loaded composite hydrogels could serve as promising candidates for diabetic wound healing treatment in the future.