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Page 2 of 14 Pignet et al. Plast Aesthet Res 2024;11:40 https://dx.doi.org/10.20517/2347-9264.2024.54

rates, as well as a reduction in the number of required dressing changes.

Conclusion: FSGs represent a safe and promising product for the management of donor sites, partial-thickness and
full-thickness burns, as well as complex trauma wounds. However, there is a paucity of high-quality clinical
evidence, especially randomized controlled trials. More research is needed to fully understand the product’s
potential for wound healing and to create a more meaningful treatment algorithm.

Keywords: Fish skin graft, Omega-3 Wound Matrix, xenograft, skin substitutes, burns, trauma, combat injuries

INTRODUCTION
Despite the rapid advancements in burn care therapies since the second half of the 20th century, successful
[1]
burn wound management still poses a challenge . Even though there is a variety of novel wound dressings
designed especially for the conservative treatment of superficial burns, a gold standard has not yet been
[2]
defined . Unlike superficial burns, deep partial- and full-thickness burns usually need to be addressed
surgically in order to prevent infections and consequent complications, such as SIRS and multiple organ
failure, and to finally achieve pleasing aesthetic and functional outcomes . Hence, early excision of necrotic
[3]
tissue followed by autologous split-thickness skin grafting (STSG) is the standard of care for deep partial-
and full-thickness burns . Extensive deep burns with > 35% total body surface area (TBSA) are especially
[3]
challenging to treat, not only due to the frequent systemic consequences, but also due to the restricted
[4]
availability of donor skin for autologous grafting . Therefore, surgeons often must rely on skin substitutes
for temporary coverage in order to reduce water, protein and heat loss and to prevent wound
colonization . Temporary wound coverage can be achieved with fully synthetic skin substitutes, with
[4]
allografts derived from human cadaveric skin, or with xenografts from mammals, such as bovine, porcine,
or fish skin . However, there are some disadvantages in using allografts and mammalian xenografts,
[5-7]
including the transmission of bacterial and viral diseases and the risk of an auto-immune response . In
[7]
light of these disadvantages, fish skin presents itself as superior. Zoonotic spillover is known to be highest in
domesticated mammals due to their phylogenetic proximity to humans and opportunity for human
contact . To fight aquatic pathogens, the body surface of fish is covered by a layer of epidermal mucus, a
[8]
viscous colloid containing antibacterial enzymes . Hence, this layer serves as a physical barrier to prevent
[9]
pathogen invasion, but it also contains factors of innate immunity, such as lysozyme, immunoglobulin,
complement proteins, C-reactive protein (CRP), proteolytic enzymes, and various other antibacterial
[9]
proteins and peptides . As marine pathogens tend to flourish in warm water, warm-water fish are exposed
to a higher pathogen load . The mucus composition and the antimicrobial component of mucus vary
[10]
[9]
between different species of fish . What is more, fish skin naturally contains Omega-3 polyunsaturated fatty
acids, eicosapentaenoic acid, and docosahexaenoic acid, which might suppress inflammation [11,12] . In vitro,
[13]
these bioactive molecules exerted antimicrobial capacity against bacteria, fungi, and viruses . Thus, they
play an important role in the acceleration of wound healing in the clinical setting.

Currently, there are two very different products derived from two distinct species of fish that are commonly
being used as wound healing matrices: Fish skin grafts (FSGs) derived from Nile tilapia (Oreochromis
niloticus) and Kerecis® Omega3 Wound Matrix (Kerecis, Isafjordur, Iceland), derived from north Atlantic
cod fish (Gadus morhua) [14-16] . Nile tilapia-derived fish skin grafts (NTG) are widely used, especially in
Brazil, and mainly for superficial partial-thickness burns (SPTB) [17-19] . According to the Food and
[14]
Agriculture Organization (FAO) of the United Nations, Nile tilapia is the most cultivated fish globally . Its
skin is obtained from local farmers and usually processed by the burn units themselves . In preclinical
[17]
studies, the morphology of NTG exhibited resemblances to human skin, featuring a thick dermis comprised
of organized collagen fibers that are arranged both horizontally and vertically. Additionally, a higher