Enriching and Smart Releasing Curcumin via Phenylboronic Acid-Anchored Bioinspired Hydrogel for Diabetic Wound Healing

Diabetic wounds suffer from bacterial infections, reactive oxygen species, and inflammatory reactions. Curcumin (Cur) is a natural diketone with antibacterial, anti-inflammatory, antioxidant activities, but poor water solubility and toxicity at high local concentration. Herein, inspired by the oxygen transport process of red blood cells via the dynamic interaction of hemoglobin and oxygen, phenylboronic acid (PBA)-anchored hydrogel (GOHA-PBA) is utilized to achieve active enrichment and smart release of Cur, which can reverse the inflammatory microenvironment and promote wound healing. First, PBA-modified gelatin (Gel-PBA) and oxidized hyaluronic acid (OHA) crosslink and form GOHA-PBA by borate ester reaction and Schiff base reaction. GOHA-PBA possesses excellent curcumin loading efficiency with 130 000 times than that in water and forms Cur-laden GOHA-PBA (GOHA-Cur). GOHA-Cur has injectability, self-healing, and self-adaptive properties, which are conducive to surgical procedure. GOHA-Cur owns reversible adhesion properties, facilitating it be peeled off and remove harmful substances, including excess glucose, acids, bacteria, and ROS at the wounds. GOHA-Cur can pH and glucose responsively release Cur; hence, it shows excellent antibacterial, antioxidant, anti-inflammatory effects in vitro. Animal experiments show that GOHA-Cur can inhibit inflammation and promote wound regeneration. This study can provide a valuable concept for Cur delivery and diabetic wound healing.