Versatile Hyaluronic Acid Hydrogels via pH-Induced Gelation for Multifaceted Cutaneous Wound Healing

Hyaluronic acid (HA) hydrogels have attracted growing interest for skin regeneration. However, conventional fabrication approaches for HA hydrogels often require complex chemical modifications, leading to prolonged preparation cycles, inconsistent batch reproducibility, and elevated toxicity. Herein, a straightforward strategy is presented for developing pure yet multifunctional HA hydrogels by regulating the pH. Specifically, highly concentrated HA solutions are initially prepared at high pH, followed by gradual neutralization mediated by the hydrolysis of gluconolactone (GdL). This pH-triggered process promotes the reformation of intermolecular hydrogen bonds, thereby culminating in a sol-to-gel transition. Owing to this unique formation mechanism, the HA-GdL (HG) hydrogels exhibit strong adhesiveness, desirable mechanical toughness, and excellent self-healing properties. Moreover, these dynamic interactions provide the HG hydrogels with injectability, moldability, and 3D printability, enabling the incorporation of therapeutic agents under physiologically benign conditions. In murine-infected wound models, silver nanoparticle-laden HG hydrogels not only conform to the irregular shape of the wounds but also exert anti-bacterial, anti-inflammatory, pro-angiogenic, and immunoregulatory effects to expedite wound closure and regeneration. Collectively, this study offers a streamlined yet highly efficient approach for fabricating versatile HA hydrogel dressings, offering significant promise for the comprehensive management of infected wounds.