Mechanisms and therapeutic insights from zebrafish models of wound healing

Abstract

Wound healing is essential for tissue integrity, yet chronic wounds remain a significant clinical challenge. The zebrafish ( Danio rerio ) offers unique advantages for studying wound repair: optical transparency enables real-time in vivo imaging, robust regenerative capacity allows scarless tissue restoration, and genetic tractability facilitates mechanistic dissection. This review synthesizes recent advances using zebrafish skin, corneal, and fin injury models, highlighting epithelial cell collective migration, the spatiotemporal dynamics of immune cell recruitment and functional conversion, and the biphasic regulatory roles of reactive oxygen species (ROS) and key signaling pathways including Wnt/β-catenin, NF-κB, and VEGF. Advanced imaging techniques—live fluorescence microscopy, polarity-sensitive probes, spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA)—are discussed for their capacity to visualize tissue remodeling and vascular regeneration. The zebrafish platform also serves as a powerful in vivo system for screening natural products, nanomaterials, and small molecules with pro-healing properties, with mechanistic insights into how these agents modulate ROS, NF-κB, MAPK, Wnt, and VEGF signaling. Finally, we address translational limitations and outline future directions integrating multi-omics and gene editing to develop novel regenerative therapies.