Establishing a Novel Immunocompromised Zebrafish Model of Delayed Skin Wound Healing to Evaluate Hydrogel Components with Phenotype Rescue Potential
Chronic wounds are a major challenge, especially in immunocompromised patients. We established a novel adult zebrafish model using Tacrolimus to mimic delayed wound healing and impaired regeneration. In this model, we tested a dynamic PVA-Borax hydrogel as a treatment. We found the hydrogel was non-toxic andeffectively restored the impaired repair capacity. Treatment promoted re-epithelialization and behavioral recovery despite the immunosuppression. Transcriptomic analysis revealed that Tacrolimus disrupted keyregeneration pathways, including extracellular matrix remodeling and cytokine signaling. The hydrogel successfully reactivated these critical immune, angiogenic, and cytoskeletal programs, reinstating coordinated tissue repair. This study introduces a robust zebrafish platform for high-throughput wound research and highlights the therapeutic potential of PVA-Borax hydrogels for restoring skin regeneration under compromised immunity.