Morpho-molecular assessment of nanomaterials in teleost fish wound healing: a systematic review.

Abstract

Background: Teleost fish skin is a vital barrier for regulating osmoregulation, immune defense, and respiration. Cutaneous wounds in farmed fish cause significant economic loss and welfare concerns, as standard treatments, like antibiotics and chemical baths, are often ineffective, toxic, and fail to adhere to mucus-covered surfaces. While nanomaterials show great promise for wound healing, current data on how they work in fish remain incomplete. This systematic review evaluates the performance of these nanomaterials, explains their healing mechanisms, and highlights the key research gaps to guide future aquaculture treatments.

Results: Following PRISMA 2020 guidelines, we included twelve in vivo studies (2017-2026). A clear shift was observed over time: research before 2020 focused only on metallic nanoparticles (silver and zinc oxide), whereas recent studies have mostly used biopolymeric nano-delivery systems. Nanoparticle treatments consistently led to faster wound closure, with several formulas healing over 90% of the wound within two weeks; however, these quantitative outcomes are strictly descriptive due to high methodological heterogeneity across studies. Under the microscope, nanomaterials accelerated re-epithelialization, improved collagen organization, and reduced inflammation. At the molecular level, they decreased pro-inflammatory cytokines (IL1β, TNFα) and matrix metalloproteinases (MMPS), while increasing anti-inflammatory markers (IL10, TGF-β) and antioxidant enzymes (SOD, CAT). Transcriptomics data also showed the activation of fibroblast growth factor 7 (FGF7) and the Jak-STAT pathways. Finally, zebrafish (Danio rerio) constituted 75% of the study models, showing a major gap in research on farmed fish like Nile tilapia (Oreochromis niloticus).

Conclusions: This systematic review shows that nanomaterials significantly accelerate teleost wound healing by promoting tissue regeneration and regulating the immune response. The shift toward biopolymeric systems, especially chitosan, indicates a clear trend toward safe and sustainable aquaculture medicine. Notably, testing hybrid nano-hyaluronic acid and nano-chitosan systems remains completely unexplored in farmed fish. This gap is important due to the complementary biological properties of these materials and the high global value of Nile tilapia. Testing this hybrid biomaterial under real farming conditions will help improve skin healing, support the immune system, and provide a safe wound treatment for global aquaculture.