Multifunctional Plasticized Hyaluronic-Acid-Based Nanogel Dressing for Accelerating Diabetic and Nondiabetic Wounds

Diabetic ulcers are associated with oxidative stress, inflammation, decreased synthesis of pro-healing mediators, and impaired vascularization, which convert the wound from acute to chronic and delay healing. An extended duration of wound healing raises the possibility of complications such as infection, sepsis, and even amputation. The objective of this study is the synthesis of a plasticized cross-linked hyaluronic acid (HA)-grafted poly(acrylamide-<i>co</i>-itaconic acid) nanogel as a nontoxic adhesive, swellable, antibacterial wound dressing with good mechanical properties to protect the wound from pathogens and accelerate the healing process, in addition to decreasing oxidative stress and inflammatory cytokines while increasing anti-inflammatory cytokines and angiogenesis. Nanogel H3 with a ratio (AM/IA) (3:1) showed excellent adhesion with good mechanical properties, biocompatibility, swelling, antioxidant, and antibacterial efficiencies. It showed great wound closure <i>in vitro</i> and <i>in vivo</i> with downregulation of inflammatory cytokines, upregulation of anti-inflammatory cytokines, and enhanced angiogenesis <i>in vivo</i> on diabetic and nondiabetic wounds.