Zebrafish as a Model System to Study the Mechanism of Cutaneous Wound Healing and Drug Discovery: Advantages and Challenges

Abstract

In humans, cutaneous wounds may heal without scars during embryogenesis. However, in the adult phase, the similar wound may undergo a few events such as homeostasis, blood clotting, inflammation, vascularization, and the formation of granulation tissue, which may leave a scar at the injury site. In consideration of this, research evolves daily to improve the healing mechanism in which the wound may heal without scarring. In regard to this, zebrafish (Danio rerio) serves as an ideal model to study the underlying signaling mechanism of wound healing. This is an important factor in determining a relevant drug formulation for wound healing. This review scrutinizes the biology of zebrafish and how this favors the cutaneous wound healing relevant to the in vivo evidence. This review aimed to provide the current insights on drug discovery for cutaneous wound healing based on the zebrafish model. The advantages and challenges in utilizing the zebrafish model for cutaneous wound healing are discussed in this review. This review is expected to provide an idea to formulate an appropriate drug for cutaneous wound healing relevant to the underlying signaling mechanism. Therefore, this narrative review recapitulates current evidence from in vivo studies on the cutaneous wound healing mechanism, which favours the discovery of new drugs. This article concludes with the need for zebrafish as an investigation model for biomedical research in the future to ensure that drug repositions are well suited for human skin.

Triphenyl phosphate-induced pericardial edema in zebrafish embryos is dependent on the ionic strength of exposure media

“…Most studies in the published literature have investigated the epithelial layer of adult zebrafish rather than embryonic zebrafish. Interestingly, these studies have looked at the capacity for cutaneous wound healing within zebrafish ( Naomi et al, 2021 ) and, as such, are difficult to compare to our results due to differences in the epithelial layer of adult vs. embryonic zebrafish. For example, embryonic zebrafish utilize the entire epithelial layer for osmoregulation due to the localization of ionocytes and aquaporins across their skin, while adult zebrafish have ionocytes and aquaporins localized to their gills, which occurs around 14 dpf ( Breves et al, 2014 ; Dymowska et al, 2012 ; Evans, 2008 , 2011 ; Gilmour, 2012 ; Hiroi and McCormick, 2012 ; Hwang and Lee, 2007 ; Hwang et al, 2011 ; Kumai and Perry, 2012 ; Wright and Wood, 2012 ).…”

Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of Aphanomyces invadans, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model

“…The zebrafish genome shares 85% sequence similarity with the human genome; it is a cost-effective model. This species has a short life cycle and is an easy model to administer/evaluate the test drugs [ 21 ]. Thus, in this study, zebrafish was used as an in vivo model for toxicity analysis.…”

Advances in Zebrafish for Diabetes Mellitus with Wound Model

“…At the same time, fibroblasts penetrate the dermis, take over the collagen produced by keratinocytes in the basal layer, form locally thickened dermal papillae, and begin to scale. In short, the skin structure of zebrafish is very similar to that of human beings, and the basic principle of the wound healing mechanism is conservative between human and zebrafish: there are discrete stages of healing, allowing specific processes to be studied separately; a remarkable ability to regenerate new fin tissue after amputation is retained, and its caudal fin has a relatively simple but symmetrical structure, including epidermis, blood vessels, nerves, pigment cells, and fibroblasts [ 39 , 79 , 80 , 81 , 82 , 83 ]. Since genetic engineering technology has developed rapidly, especially in CRISPR-Case9 (efficient multiple gene targeting, zebrafish mutant strain breeding, etc.…”