Gelatin-based adaptive injectable nanocomposite hydrogel for closure of irregular wounds and immunoregulation in diabetic wound healing.

Chronic wounds are a major challenge in diabetic patients, exacerbated by disorders of blood perfusion and angiogenesis, bacterial infection, oxidative stress, and inflammation and immune imbalance. Bioactive hydrogels with multifunctional immunomodulatory properties offer promising solutions for diabetic wound management. However, many hydrogels lack adaptability and rely on costly cytokines, cell therapies, or drugs with side effects. This study introduces a novel gelatin-based injectable nanocomposite hydrogel (GelDE-OCS@MOF@Pl) for irregular wound closure and diabetic ulcer healing. This naturally derived macromolecular hydrogel exhibits exceptional biocompatibility and in situ molding capabilities, enabling effective closure and repair of irregular wounds. The GelDE-OCS@MOF@Pl hydrogel serves dual therapeutic functions by establishing a protective physical barrier while intelligently regulating polyphyllin (Pl) release in response to pH variations, thereby simultaneously eliminating bacterial pathogens, scavenging reactive oxygen species, and suppressing excessive inflammation for providing a suitable microenvironment for angiogenesis and epithelialization. This nanocomposite hydrogel effectively promotes diabetic wound healing through coordinated modulation of the wound immune microenvironment, demonstrating multifunctional therapeutic effects including antibacterial activity, oxidative stress alleviation, and anti-inflammatory action, thereby presenting a promising treatment strategy for chronic diabetic wounds.