Conductive hydrogel with responsive release of Herbal-Derived carbon dots for neurovascular reconstruction in diabetic critical limb ischemia

Abstract

Diabetic critical limb ischemia (CLI), a common complication of diabetes with high morbidity and amputation rates, has seriously endangered the patients’ health and quality of life. Diabetic CLI is commonly characterized by inflammatory imbalance, vasculopathy, and neuropathy, which significantly impede tissue regeneration. Most biomaterials offer limited angiogenic functions, of which neuropathy treatment is still in its infancy. Herein, we report a composite conductive hydrogel (MSC@COP) by combining the salidroside-derived carbon dots (CDs)-embedded magnesium silicate nanoflowers (MSC) with the PEDOT:PSS-based hydrogel. Responding to the low-pH environment of diabetic CLI, CDs and magnesium ions (Mg²⁺) are released to scavenge reactive oxygen species in the ischemic microenvironment and promote the M1-to-M2 polarization of macrophages to reshape the inflammatory environment. Meanwhile, the high conductivity of the hydrogel conferred by PEDOT:PSS not only repairs the endogenous electric field but also synergizes with CDs and Mg²⁺ to inhibit Schwann cell pyroptosis, improve the recruitment of Schwann cells, consequently promoting the dual reconstruction of neural and vascular tissues.