Multi-functional phytoglycogen-derived hydrogel dressings promote the fast closure of diabetic wound in vitro and in vivo

Abstract Management of chronic diabetic wound was an emerging challenge, and designing a multi-functional hydrogel to promote wound repair is urgent for therapy. We firstly discovered a natural hydrogel dressing from modified phytoglycogen (PG) with cationization and oxidation for the Schiff base cross-linking. In vitro and in vivo studies reveal the hydrogel exhibited the favorable adhesion, self-healing, antibacterial and antioxidant properties, and the optimal CPG2-Gel forms efficient coverage in wound without contamination and infection. In the diabetic wound model, CPG2-Gel expedited the reactive oxygen species (ROS) clearance and immunoregulation, promoting cell proliferation, collagen deposition, and tissue formation to facilitate the wound closure with the healing rate of 1.76-fold compared to commercial dressing. The tumor necrosis factor-α (TNF-α) level was reduced to 87.5%, whereas the vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were enhanced up to 1.36 and 2.01 times, respectively. The mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways played crucial roles in mediating the polarization of alternatively activated macrophages (M2 macrophages), thereby facilitating cell proliferation, exerting anti-inflammatory effects, and regulating immune responses. This work can provide a facile and promising strategy for fabricating a multifunctional hydrogel dressing for fast therapy of diabetic wound.