ZIF-8-Based Smart-Responsive Nanocomposites for Cutaneous Wound Healing: A Review

Cutaneous wound healing is a complex process that requires precise management. In recent years, intelligent, responsive biomaterials have played a crucial role in guiding wound healing through these stages in a physiologically ordered manner. Zeolitic imidazolate framework-8 (ZIF-8), a subclass of metal-organic frameworks (MOFs), has received extensive attention in the biomedical field due to its intrinsic pH-responsive biodegradability, adjustable porosity and surface area, inherent antibacterial activity, and excellent biocompatibility. This Review provides a comprehensive and systematic overview of recent advances in ZIF-8-based smart-responsive nanocomposites for cutaneous wound repair. We first elaborate on the multifunctional roles of ZIF-8 across distinct phases of the wound healing cascade, including anti-infection, hemostasis, inflammation, proliferation, and remodeling. Subsequently, we critically discuss diverse delivery strategies employing ZIF-8 as a nanocarrier for therapeutic agents such as natural extracts, metals and their derivatives, biomacromolecules, functional drugs, and bioactive gases. A particular focus is placed on intelligent, responsive modifications of ZIF-8-based nanocomposites, which enable on-demand drug release and adaptive functionality in response to specific wound microenvironmental cues, including internal stimuli (temperature, pH, reactive oxygen species (ROS), glucose, and ATP) and external stimuli (light, magnetic fields, and ultrasound). Diverse application forms of ZIF-8 nanocomposites are extensively discussed, encompassing hydrogels, electrospun membranes, and microneedle patches. Finally, we present tailored design strategies of smart-responsive ZIF-8-based biomaterials for different wound scenarios, including diabetic wounds, infected wounds, burn injuries, and penetrating trauma. This Review aims to offer valuable insights and practical guidance for the rational design of next-generation intelligent wound care systems, while addressing current challenges and future perspectives in clinical translation.