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Pignet et al. Plast Aesthet Res 2024;11:40 https://dx.doi.org/10.20517/2347-9264.2024.54 Page 3 of 14

proportion of type I collagen, along with elevated resistance and tensile strength, was observed compared to
[14]
human skin . Being a warm-water fish, it requires harsher processing than cold-water fish, including
[17]
chemical sterilization, glycerolization, and gamma irradiation . Until today, this product has not been
commercially available. However, it acts as an important cost-effective tool in burn care management,
especially in developing countries, where 90% of burn injuries occur .
[18]
Kerecis® Omega3 Wound Matrix, on the other hand, is Food and Drug Administration (FDA)-approved
and available worldwide. As it is a cold-water fish, there is a negligible risk of transmitting diseases to
humans, which allows for gentler processing, without any harsh chemicals that dissolve the soluble
components of the tissue . The result is a decellularized matrix with otherwise preserved dermal
[11]
microarchitecture. The structural integrity and the molecular components of the skin including the
proteoglycans, glycoproteins, soluble collagen, elastin, laminin, fibronectin, lipids, and the Omega-3
polyunsaturated fatty acids are retained [11,20] . Additionally, the product demonstrates a heterogeneous pore
[6]
structure to efficiently endure external tensile stress and allow for vascular ingrow . Yoon et al. conducted
an in vitro study to compare cell growth under the influence of the Kerecis® Omega3 Wound Matrix and a
bovine collagen wound matrix (ProHeal®, MedSkin Solutions, Germany) . The cell density after days 1 and
[6]
3 was significantly higher with the Kerecis® Omega3 Wound Matrix, which indicates a faster creation of new
[6]
tissue and, consequently, better skin regeneration . Lastly, the Kerecis® Omega3 Wound Matrix is easy to
use and can be preserved up to three years after production, which is beneficial when the cold chain is
[20]
interrupted, which is often the case in military contexts .

Due to their numerous beneficial properties, FSGs are commonly used to treat chronic wounds, as well as
complex acute wounds, such as combat injuries, and burns across various countries worldwide [16,18,20,21] .
Nonetheless, a systematic review from 2022 found only a scarce body of literature on the effects of FSGs on
wound healing in burns . In the present systematic review, we aimed to give an update on clinical studies
[7]
investigating the effects of the two above-mentioned FSGs (Kerecis® Omega3 Wound Matrix and NTG) on
healing for the following indications: donor sites from split-thickness skin grafts, superficial and deep
partial-thickness burns, full-thickness burns, combat wounds, and other acute wounds.

METHODS
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) statement (PROSPERO ID: CRD42024500798) .
[22]

Search strategy and article selection
A systematic search of two databases, PubMed and Web of Science, was performed in January 2024 by two
authors (A.H. and A.L.P.) for literature published in any year related to clinical studies that used acellular
fish skin in the context of burns or complex trauma wounds. The following search terms were used: (“fish
skin” OR “fish skin graft” OR “acellular fish skin” OR “acellular fish skin graft” OR “marine graft” OR
“North Atlantic Cod” OR “Nile Tilapia”) AND (“trauma*” or “burn*” or “injur*” or “war” or “militar*” or
“explosion*”).

Based on the search terms, both authors independently screened the study titles, abstracts, and, if available,
full-text articles. Only human-based clinical studies published in English that involved the use of acellular
fish skin for treating burns or complex trauma wounds were included. Articles including preclinical studies
(e.g., laboratory work, animal experiments), reviews, commentaries, or letters were excluded. Both authors
independently recorded all search results and available clinical data in an Excel spreadsheet (Microsoft Excel
2016, Microsoft Office [16.44] 32-bit). Afterwards, the extracted data were compared and reconciled. In