ArticlePDF Available

The Utility of Novel Fish-Skin Derived Acellular Dermal Matrix (Kerecis) as a Wound Dressing Material

Authors:
Article

The Utility of Novel Fish-Skin Derived Acellular Dermal Matrix (Kerecis) as a Wound Dressing Material

Abstract and Figures

Background: The newly-approved Kerecis is a piscine acellular dermal xenograft. This piscine acellular dermal matrix (ADM) has specific bioactive lipid mediators, omega-3 polyunsaturated fatty acids, and has a positive effect on the process of wound healing. This study aimed to explore the utility of this novel material by comparing healing rates, and suggest the proper timing for applying Kerecis. Methods: Patients who visited the hospital with acute or chronic deep dermal wounds from June 2019 to May 2020 were enrolled in the study. A total of 48 patients were assessed. All wounds in the experimental group (n=16) were treated only once with Kerecis and a non-adherent absorptive foam material (Therasorb) to cover the ADM. In the control group, daily conventional dressings were provided. All wounds sizes were measured with mass-market computer software in a method suggested by the authors for the first time. Results: The mean healing rate proved to be faster in the Kerecis group (P<0.05) versus the control group, and no complications were observed. It was statistically proved that treating burn wounds with the ADM showed better healing rates than the conventional method (P<0.05). Conclusion: This study establishes that managing wounds with the ADM is likely to heal wounds faster than traditional dressings. In addition, for burn wounds, a prolonged application (10 days vs. 5 days after the onset) showed a better wound healing rate (98.8%±2.5% vs. 67.0%±14.3%, respectively, P=0.029).
www.jwmr.org 39
Introduction
In general, wounds are classied into two types depending on the progress of healing:
acute and chronic. Improper wound management causes delayed wound healing,
which leads to chronicity. A wound is for the most part considered chronic if it has
not healed in 4 weeks. Delayed wound healing is also oen associated with complica-
tions such as infections, scar formation, and incomplete wound healing.
Whether the wound is caused by direct trauma or a burn, proper wound manage-
ment is one of the essential concerns for early wound healing. In general, wound
management contributes to the healing process by protecting the wound uids, pre-
venting infection, controlling mechanical influences, and influencing the collagen
maturation course. Physiologically, growth factors, chemokines, cytokines, and their
receptors are critical in normal wound healing [1,2].
Many therapies promoting early wound healing by accentuating spontaneous heal-
ing at molecular levels have been recently introduced. Acellular dermal matrix
(ADM) is one of such treatments, and it has shown potential for accelerating wound
healing. ADM helps wound healing by stimulating angiogenesis, and providing a
Original Article
Received: July 31, 2020
Revised: November 30, 2020
Accepted: November 30, 2020
Corresponding author:
Syeo Young Wee, M.D.
Department of Plastic and Reconstructive
Surgery, Soonchunhyang University Gumi
Hospital, 179 1(il)gongdan-ro, Gumi 39371,
Korea
Tel: +82-54-468-9150
Fax: +82-54-463-7504
E-mail: 94061@schmc.ac.kr
This is an Open Access article distributed under the terms
of the Creative Commons Attribution Non-Commercial
License (https://creativecommons.org/licenses/by-nc/4.0/)
which permits unrestricted non-commercial use, distribution,
and reproduction in any medium, provided the original work
is properly cited.
© 2021 Korean Wound Management Society
J Wound Manag Res 2021 February;17(1):39-47
https://doi.org/10.22467/jwmr.2020.01228
Journal of Wound Management and Research
The Utility of Novel Fish-Skin Derived Acellular
Dermal Matrix (Kerecis) as a Wound Dressing
Material
Tae Hyung Kim , Jun Ho Park , Hyun Gyo Jeong , Syeo Young Wee
Department of Plastic and Reconstructive Surgery, Soonchunhyang University Gumi Hospital, Gumi, Korea
Abstract
Background: The newly-approved Kerecis is a piscine acellular dermal xenograft. This piscine acellular dermal matrix (ADM) has specific
bioactive lipid mediators, omega-3 polyunsaturated fatty acids, and has a positive effect on the process of wound healing. This study aimed
to explore the utility of this novel material by comparing healing rates, and suggest the proper timing for applying Kerecis.
Methods: Patients who visited the hospital with acute or chronic deep dermal wounds from June 2019 to May 2020 were enrolled in the
study. A total of 48 patients were assessed. All wounds in the experimental group (n= 16) were treated only once with Kerecis and a non-
adherent absorptive foam material (Therasorb) to cover the ADM. In the control group, daily conventional dressings were provided. All
wounds sizes were measured with mass-market computer software in a method suggested by the authors for the first time.
Results: The mean healing rate proved to be faster in the Kerecis group (P <0.05) versus the control group, and no complications were ob-
served. It was statistically proved that treating burn wounds with the ADM showed better healing rates than the conventional method
(P < 0.05).
Conclusion: This study establishes that managing wounds with the ADM is likely to heal wounds faster than traditional dressings. In addi-
tion, for burn wounds, a prolonged application (10 days vs. 5 days after the onset) showed a better wound healing rate (98.8% ±2.5% vs.
67.0% ±14.3%, respectively, P =0.029).
Keywords: Acellular dermis; Wound healing; Burns; Injuries
pISSN 2586-0402
eISSN 2586-0410
Kim TH et al.
The usefulness of Kerecis
40 www.jwmr.org https://doi.org/10.22467/jwmr.2020.01228
scaold for granulation tissue formation [3]. Many kinds of
ADM products have been reported to promote tissue regener-
ation and wound healing, and are in wide clinical use, such as
AlloDerm from human skin (LifeCell Crop.), Integra from
bovine tendon type I collagen (Integra Lifesciences) and EZ
Derm from porcine aldehyde cross-linked dermal collagen
(Molnlycke HealthCare).
Most recently, a novel acellular sh-skin gra product, Kere-
cis Omega3 (Kerecis), has become commercially available. It
was already approved from the Food and Drug Administration
in the United States in 2016. e material had obtained clear-
ance from the Ministry of Food and Drug Administration in
Korea in 2018 as well. We therefore aimed to investigate the
utility of this novel material as a dressing material, comparing
healing rates between a Kerecis-applied group and a control
group. We also attempted to suggest the proper timing to apply
Kerecis.
Methods
Patients who visited the emergency department or the outpa-
tient clinic, from June 2019 to May 2020, with acute or chronic
wounds of the deep dermal layer were recruited for this study
(Fig. 1). We retrospectively surveyed the patient’s age, sex,
smoking status, wound location, and categorized the wounds
[4]. For acute wounds, we dierentiated them by the causes of
injury, into either burn or trauma. Patients treated with ADM
or conventional dressings were chosen by patients preference.
e 32 patients in the control group were enrolled in a retro-
spective cohort during the same period. None of the patients
were placed on medical or surgical treatment for faster wound
healing. Patients who underwent surgery during the study pe-
riod or failed to appear for follow-up were excluded. Demo-
graphic values in the ADM group were summarized in Tables
1 and 2. ere were no signicant dierences among the pa-
tients in other factors such as diabetes, hypertension, smoking,
age, sex, and location
Wound dressing using Kerecis
The application of Kerecis (Kerecis, Isafjordur, Iceland) was
dierentiated according to certain criteria. For acute wounds,
the ADM was applied around 2 days aer the onset of injury
when the amount of discharge from each wound suciently
diminished. For acute burn wounds, it was applied later than
acute traumatic wounds, i.e., later than 5 days aer the onset,
because the discharge from burn wounds is typically more
than that of acute wounds. Normally, burn wounds initially
have excessive discharge that is likely to impede the eective
wound healing of Kerecis.
The Kerecis Omega3 wound matrix was applied on the
wound as follows. First, we removed most of the necrotic tis-
sue, measured the size of fresh tissue surface, and cut the ma-
terial 1 mm to 2 mm larger than the wound to cover the wound
margin. e cut material was then bathed in saline solution
for 60 seconds at room temperature. The Kerecis sheet was
then directly applied on the wound, its rough side face down.
Lastly, a non-adherent absorptive foam material (erasorb 5
mm) was used to cover the ADM (Fig. 2). Wounds were treat-
ed only once with Kerecis; those that were managed with other
dermal substitutes were excluded. Foam change was per-
Fig. 1. Patient selection process.
16 Patients 41 Patients
32 Patients
Total 57 Patients
Acute & chronic deep dermal layer wounds
9 Patients
Surgical intervention, follow-up loss
Kerecis application Conventional dressing
Control group
Kim TH et al.
The usefulness of Kerecis
www.jwmr.org 41
https://doi.org/10.22467/jwmr.2020.01228
formed daily aer the ADM was used. In the control group,
the wound was covered with the same foam material aer ap-
plying antibiotic ointment once a day.
Clinical outcomes
Digital images, including a ruler (cm scale) within the frame
of each image, were photographed with a Canon D750 Cam-
Table 1. Patients with acute or chronic wounds in the Kerecis group
Patient
No. Sex Age
(yr) Cause Types of
injuries
Personal
history Location Application
timing (day)
Healing
rate (%) Dischargea) Complication
1 M43 Machinery injury Trauma HTN Right thumb 382.94 +No
2 F39 Knife injury Trauma -Left 3rd nger 294.95 +No
3 M89 Venous insufciency Spontaneous -Right great toe 2 wk 73.32 +++ No
4 M30 Glass injury Trauma -Forehead 270.02 +No
5 M49 Knife injury Trauma -Right thumb 263.48 +No
6 F56 Hot water Burn HTN Right lower leg 563.72 +No
7 F84 Hot water Burn DM Left heel 583.00 +No
8 M52 Diabetic gangrene Spontaneous DM Right 5th toe 2.5 wk 43.53 ++ No
9 M61 Slip down Trauma HTN Left lower leg 346.39 +++ No
10 F50 Pressure sore Spontaneous DM Left heel 1 mon 77.38 +++ No
11 F 7 Hot water Burn -Left thumb 12 99.36 ++ No
12 F62 Hot water Burn HTN Right ankle 10 99.99 +No
13 F11 Hot material Burn -Right forearm 685.85 ++ No
14 F11 mon Hot material Burn -Right hand 11 98.05 +++ No
15 F25 Hot water Burn -Left thigh 10 97.94 +No
16 F35 Hot material Burn -Left forearm 564.61 +++ No
M, male; F, female; HTN, hypertension; DM, diabetes mellitus.
a)The amount of initial wound discharge.
Table 2. Total comparison of each group
Criteria Conventional group Kerecis group P-value
Age (yr) 42.0±21.1 43.3±25.2 0.328
Sex (M/F) 15/17 11/5 0.381
Diabetes 0.480
Yes 9 3
No 23 13
Hypertension 1.000
Yes 8 4
No 24 12
Smoking 0.297
Yes 11 8
No 21 8
Type of injuries 0.053
Trauma 11 5
Burn 15 8
Spontaneous 6 3
Location 2.580
Face 4 1
Lower extremity 21 8
Upper extremity 7 7
Values are presented as mean± SD or number.
M, male; F, female.
Fig. 2. The rough surface of Kerecis.
Kim TH et al.
The usefulness of Kerecis
42 www.jwmr.org https://doi.org/10.22467/jwmr.2020.01228
era at a resolution of 6,000×4,000 pixels by a single trained
photographer. In order to measure the wound sizes, based on
clinical photos, their size and depth were assessed by three dif-
ferent board-certied plastic surgeons (SYW, HGJ, and JHP)
(Fig. 3). e three reviewers all evaluated the wound as com-
pletely healed when it recovered with full epithelialization, and
as healing state when it started to form healthy granulation tis-
sue [5]. To measure the size of the wounds, the digital photos
were opened on Adobe Photoshop version 21.2.4 (Adobe,
California, LA, USA) and the areas of the initial wounds and
epithelialized wounds were calculated by their number of pix-
els [5-7]. We compared the initial wound size when Kerecis
was applied, with the wound size at 7th post-application day.
e healing rate was calculated by the change in epithelializa-
tion over the course of a week in each group (Fig. 4) [7,8]. We
represented and recorded the progress of the wound based on
clinical photography. In addition, the number of days until full
recovery was recorded. e wounds were also examined for
complications such as infection and dermal component loss
for further follow-up in 2 months.
is study was approved by the Institutional Review Board
of Soonchunhyang University Gumi Hospital (IRB No. 2020-
04) and performed in accordance with the principles of the
Declaration of Helsinki. Proper informed consent was ob-
tained and each patient was provided with an explanation of
the procedure.
Analysis
Variables in such a study are typically presented in values of
mean and standard deviation. To compare the mean values,
the Mann-Whitney U test was used because the sample size
was small. Regression analysis was performed to estimate rela-
tionships between a dependent variable and one or more inde-
pendent variables. Statistical analyses were performed using
IMB SPSS Statistic version 27.0 (IBM Corp., Armonk, NY,
USA).
Results
A total of 48 patients with acute and chronic deep dermal-lay-
ered wounds were enrolled. Of the 16 patients in the ADM
group, 10 were women and six were men with ages ranging
from 0 to 89 years (mean, 43.3± 25.2 years). ere were eight
acute burns, and ve wounds in the acute stage created by di-
rect trauma such as knife, machine, and glass. Of the other
three chronic wounds, one patient had a diabetic foot ulcer on
his right h toe, one had developed a wound on his right great
toe due to venous insuciency, and one had a pressure sore on
her le heel. e average treatment duration in the ADM group
was 10.1±5.5 days. e ADM was applied 2 to 3 days (average,
2.40±0.55 days) aer the onset of the injury in traumatic acute
wounds. For burn wounds, the application was later, from 5 to
12 days (average, 8.00± 3.02 days) aer the onset.
The Kerecis was not fully absorbed until an average of
5.56±1.60 days aer its application. e average healing rate
was 77.7%±18.2%, which was measured on when Kerecis was
fully absorbed, which was 2 weeks aer starting treatment.
e mean healing rate for the traumatic acute wound was
Fig. 3. Wound size measurement by three different reviewers.
Initial wound size (red line), epithelialized area (blue line),
granulation tissue (yellow line). (A) Reviewer 1. (B) Reviewer
2. (C) Reviewer 3.
A B
C
Kim TH et al.
The usefulness of Kerecis
www.jwmr.org 43
https://doi.org/10.22467/jwmr.2020.01228
71.4%±18.4% when Kerecis was fully absorbed aer its appli-
cation, and 52.7%± 24.1% in the control, which represented
no statistical dierence (P= 0.310). For the burn wounds, the
mean healing rate was 86.5%± 15.2% in the ADM group and
61.1%±20.7% in the control group (P=0.021). The average
healing rate of all wounds with the ADM application in this
study was 77.7%± 18.2% and 53.3%± 22.0% for the control
group, demonstrating statistical signicance with a P-value of
<0.05. e aforementioned information is summarized in Ta-
bles 3 and 4, representing the rate of healing for each type of
wound.
Meanwhile, for the burn wounds, the mean healing rate for
the wounds on which Kerecis was applied over 10 days (n= 4)
aer the onset of injury was 98.8%± 1.0%, which is much faster
compared to the burn wounds (average, 74.2%± 11.7%; n=4)
treated with the ADM 5 days aer the onset (P<0.05).
Case 1
A 43-year-old male patient was injured on the thumb by a ma-
chine. He showed an avulsive laceration on his right thumb.
Fig. 4. The calculation of the healing rate. (A) The formula of healing rate in this study. (B, C) The size of the wound was assessed by
our new method of measuring wound sizes using computer software. SA, initial surface area; SB, day 7 surface area. Raw surface
tracing (dotted line), pixel counts (red arrows).
A
B
C
Photo at 7th day
B=Pixel counts of residual raw surfaces
y=Pixel counts of standardized (1× 0.5 cm) ruler
Photo at initial wound
A=Pixel counts of initial wound
Treatment
x=Pixel counts of standardized (1× 0.5 cm) ruler
Kim TH et al.
The usefulness of Kerecis
44 www.jwmr.org https://doi.org/10.22467/jwmr.2020.01228
e avulsed ap was necrotized and had a deep dermal layer
skin defect, 2×1 cm in size. e proximal portion of the defect
was primarily closed with nylon number 5-0, and Kerecis was
applied on the tip of the defect 3 days aer the injury. A week
after application, 87.5% epithelialization was observed. The
Kerecis remained in place for up to 7 days, promoting wound
healing. Additional dressing was performed, and 13 days aer
the injury, the wound healed completely (Fig. 5).
Case 2
A 56-year-old female patient experienced a hot water burn in-
jury. She suffered from a deep second-degree burn on her
right lower leg. e wound was nearly 7×2 cm in size and af-
fected the deep dermal layer with a whitish change on the
wound bed. e ADM was applied 5 days aer the injury, and
the wound was epithelialized by 71.4% at 7th day aer the rst
application. e Kerecis was fully absorbed aer 5 days. e
wound healed completely 14 days aer the application of the
Kerecis (Fig. 6).
Table 3. Comparison of healing rate and duration among the
causes of injuries
Cause
Healing rate, mean±SD
P-value
Kerecis
group
Conventional
group
Burn 86.5±15.2 55.7 ±17.1 <0.05
Trauma 71.4± 18.4 55.7± 16.4 0.11
Spontaneous 64.7 ±18.4 27.9 ±7.9 0.03
Total 77.7± 18.2 50.5± 18.7 <0.05
Table 4. Comparison between wound types in the Kerecis group
Cause No. Healing rate, mean ±SD P-value
Burn 886.5±15.2 0.093a) 0.225b)
Trauma 571.4± 18.4
Spontaneous 364.7±18.4
Total 16 77.7±18.2
a)Burn vs. trauma; b)Burn vs. trauma vs. spontaneous.
Fig. 6. Acute burn wound on the lower leg. (A) At the time of initial application of the acellular dermal matrix (ADM). (B) Three days
after application. (C) Five days after application, the ADM was fully absorbed.
Fig. 5. Acute trauma wound on the thumb. (A) At the time of initial application of the acellular dermal matrix (ADM). (B) Three days
after application. (C) Eight days after application, the ADM was fully absorbed.
A B C
A B C
Kim TH et al.
The usefulness of Kerecis
www.jwmr.org 45
https://doi.org/10.22467/jwmr.2020.01228
Discussion
ADM is widely used in managing various types of wounds.
ADMs that are derived from cadaveric or pig skin can trigger
a series of autoimmune reactions and transmit viral and bacte-
rial disease, while also being costly [9]. In fact, the main disad-
vantage of using ADMs among options of wound manage-
ment is their price (Table 5). However, the cost of Kerecis is
relatively low compared to other ADMs.
Kerecis, a newly-approved ADM, is a piscine acellular der-
mal xenogra, which is derived from the Atlantic cod (Gadus
morhua) [10,11]. Fish skin shows architectural similarities to
mammalian skin, owing to its molecular structure [9,10,12].
Kerecis maintains its three-dimensional structure composed
of glycosaminoglycans, proteoglycans, bronectin, and growth
factors [9]. ese lipid mediators are also preserved through
the special manufacturing process of Kerecis [10]. Further-
more, the product has specic bioactive lipid mediators called
omega-3 polyunsaturated fatty acids, which are a distinct fea-
ture of piscine ADM.
It has been reported in previous studies that the omega-3
matrix contributes to the process of wound healing. Baldurs-
son et al. [13] found that treatment with the omega-3 matrix
compared to that with porcine matrix (Oasis) caused no sero-
conversions in autoantibodies and healed much faster. Mag-
nusson et al. [11] concluded that application of the omega-3
matrix in acute complicated wounds shows a 50% mean re-
duction in wound area in the early stage of healing. Further-
more, studies by Yang et al. [12] proved that the omega-3 ma-
trix was a promising material in managing chronic wounds
including diabetic foot ulcers, and a 48% decrease in wound
depth was observed aer 5 weeks of application of the sh-de-
rived ADM.
Kerecis provides a complex scaold that gives the optimal
environment for a positive host tissue response, characterized
by restoration of tissue structure and function, while deliver-
ing anti-inammatory eicosapentanoic acid and docosahexa-
noic acid type omega-3 fatty acids [12]. Studies have demon-
strated that omega-3 fatty acids serve as inammation regula-
tors [9], promote antibacterial activity against Gram-positive
and Gram-negative bacteria, and also antiviral activity against
human immunodeciency virus and herpes simplex viruses
[10]. Magnusson et al. [14] reported that fish-skin graft has
healthy antibacterial activity compared with human amnion/
chorion membrane allogra: the acellular sh-skin gras can
withstand bacterial invasion for up to 48–72 hours. In addi-
tion, in vitro studies show that acellular sh-skin gras fur-
thermore exert an immunomodulatory effect by inhibiting
macrophage secretion of the proinammatory cytokine inter-
leukin 1-beta [13]. Given the literature, we assumed that man-
aging chronic wounds with Kerecis would have a better heal-
ing rate than the control group, and proved the ecacy statis-
tically. Further research using Kerecis comprising a large
number of chronic wounds is expected to support our ndings
on its ecacy on chronic wounds.
e microporous structure (i.e., pores of less than 2 nm in
diameter) of Kerecis allows autologous cells and capillaries to
migrate and promote epithelialization. In addition, it has been
described to be useful in covering deep dermal layer wounds,
such as wounds sustaining loss of full-thickness skin, for ex-
ample in injuries where the bone or tendon is exposed [10].
To further verify the ecacy of Kerecis in wound manage-
ment as was investigated in preceding studies, we found how
eectively it acted on a variety of wounds by dierentiating the
timing of Kerecis application. e right time for application
tends to be later in acute burn wounds than in acute traumatic
wounds, and is more delayed in chronic wounds compared to
acute burn wounds (Table 6). This tendency is attributed to
the quantity of discharge from each type of wound. e more
discharge, the more meticulous the physicians’ dressings were,
and the faster Kerecis was absorbed. Meanwhile, keeping Ker-
ecis longer on the wound surface turned out to not speed up
the healing rate (P= 0.217). For fast and ecient dressing, it is
recommended to start to apply the ADM when discharge is
moderate.
In this study, we applied Kerecis in specic wounds of the
deep dermal layer and found a decent healing rate of more
than 70% when the ADM was fully absorbed.
e application of Kerecis on acute burn wounds showed
better progress in terms of wound healing rates compared to
acute traumatic wounds, albeit without statistical signicance
(P=0.435). Overall comparison of healing rate between the
two groups demonstrated that using Kerecis (P<0.05) was
Table 5. Acellular dermal matrix cost considerations
Product Source Dimensions (cm) Unit cost (KRW)a)
Kerecis Piscine 3 ×3.5 126,500
AlloDerm Human 2×4 233,920
Integra Bovine 5×5 162,800
a)Unit cost based on an exchange rate of South Korean Won (KRW) 1,100= US 1
dollar.
Kim TH et al.
The usefulness of Kerecis
46 www.jwmr.org https://doi.org/10.22467/jwmr.2020.01228
more ecient. In particular, our stratication analysis revealed
that managing burn wounds with the ADM had much better
results (P< 0.05). In addition, we found that the delayed appli-
cation of Kerecis on acute burn wounds, later than 10 days,
had better outcomes (Table 7). This study controlled con-
founding variables by randomization during the study period.
Independent variables such as personal medical history and
the locations and types of wounds were excluded, based on
Pearson chi-square test (Tables 1, 2).
Several approaches have been developed and used in clinical
and basic research to measure the shape of wounds [5,6,15],
from the traditional approach using transparent lm to trace
the outline of the wound, to use of computer-based soware.
None has proved to be superior to others in terms of accuracy
and eciency. Although the three-dimensional shape and col-
or of the wound can be obtained and measured using a laser
projector and camera [15], it is expensive and not ecient for
clinical use [16], also requiring special software and instru-
ments. In this study, we referred to the study by Li et al. [6] for
pixel-based wound measuring, and calculated the healing rate
on the mass-market Adobe Photoshop program. However,
while in Li’s study the authors included much data into a single
image and compared them by counting pixels [6,16], we used
a reference ruler and the simple program to measure disparate
images traced when we rst examined the patient and, on the
7th posttreatment day (Fig. 3), introducing a new method of
measuring wounds.
The limitations of this study include its small sample size
and the attributes of a retrospective study covering a short pe-
riod of time. Also, the factors inuencing healing rate such as
nutrition, stress level, alcoholism, and so on were not evaluat-
ed because the data in the study was collected from chart re-
views [4]. Furthermore, the timing of ADM application dif-
fered among the types of injuries, which would have aected
the outcomes. In addition, the depth of the wounds was not
evaluated by histopathology, and neither were indications for
application of the ADM evaluated. A larger number of cases
included in a long-term study is required to increase the reli-
ability of the results.
While no previous literature has reported the efficacy of
Kerecis for dierent types of injury, our study provides for the
rst time dierent progress rates and durations of healing aer
the application of Kerecis in acute and chronic wounds. In ad-
dition, this article suggests the ideal application timing of Ker-
ecis in acute burn wounds.
ADM is widely used in managing wounds. Its use acceler-
ates wound healing and helps diminish wound complications.
A novel acellular sh-skin gra product, Kerecis Omega3, is
commercially available. Our study found that managing
wounds with the piscine ADM is more effective than with
conventional dressings. In addition, we suggest that applica-
tion of the ADM in managing burn wounds should be delayed
until discharges are suciently reduced. A 10-day postburn
delayed application showed a better wound healing rate than
applying the ADM 5 days aer the onset.
Conflict of interest
is work was supported in part by the Soonchunhyang Uni-
versity Research Fund. Otherwise, no potential conict of in-
terest relevant to this article was reported.
ORCID iDs
Tae Hyung Kim https://orcid.org/0000-0001-9537-2330
Jun Ho Park https://orcid.org/0000-0003-0235-1261
Hyun Gyo Jeong https://orcid.org/0000-0002-6378-6093
Syeo Young Wee https://orcid.org/0000-0002-1787-9715
Table 6. Simple regression analysis
Dependent variable Variable Criteria P-value
Kerecis application timing (day) Discharges Mild= 1, moderate= 2, severe= 3 0.032
Type of wounds Acute burn= 1, acute traumatic= 2, chronic stage= 3 < 0.001
Kerecis duration (day) Discharges Mild=1, moderate =2, severe =3 0.03
Healing rate (%) Kerecis duration Days until Kerecis is fully absorbed 0.344
Table 7. Comparison of healing rate and duration in burn wounds
Cause Application
timing No. Healing rate, mean±SD
(Kerecis group) P-value
Burn <5 Days 474.2± 11.7 <0.05
>10 Days 498.8± 1.0
Kim TH et al.
The usefulness of Kerecis
www.jwmr.org 47
https://doi.org/10.22467/jwmr.2020.01228
References
1. Falanga V. Wound healing and its impairment in the dia-
betic foot. Lancet 2005;366:1736-43.
2. Whiddon LL. The treatment of venous ulcers of the lower
extremities. Proc (Bayl Univ Med Cent) 2007;20:363-6.
3. Aramwit P. Introduction to biomaterials for wound heal-
ing. In: Agren MS, editor. Wound healing biomaterials.
Cambridge: Woodhead Publishing; 2016. p. 3-26.
4. Guo S, Dipietro LA. Factors affecting wound healing. J
Dent Res 2010;89:219-29.
5. Santamaria N, Ogce F, Gorelik A. Healing rate calculation
in the diabetic foot ulcer: comparing different methods.
Wound Repair Regen 2012;20:786-9.
6. Li PN, Li H, Wu ML, et al. A cost-effective transparency-
based digital imaging for efficient and accurate wound area
measurement. PLoS One 2012;7:e38069.
7. Lundeberg TC, Eriksson SV, Malm M. Electrical nerve
stimulation improves healing of diabetic ulcers. Ann Plast
Surg 1992;29:328-31.
8. Cukjati D, Rebersek S, Miklavcic D. A reliable method of
determining wound healing rate. Med Biol Eng Comput
2001;39:263-71.
9. Alam K, Jeffery SLA. Acellular fish skin grafts for manage-
ment of split thickness donor sites and partial thickness
burns: a case series. Mil Med 2019;184(Suppl 1):16-20.
10. Dorweiler B, Trinh TT, Dunschede F, et al. The marine
Omega3 wound matrix for treatment of complicated
wounds: a multicenter experience report. Gefasschirurgie
2018;23(Suppl 2):46-55.
11. Magnusson S, Kjartansson H, Baldursson BT, et al. Acellu-
lar fish skin grafts and pig urinary bladder matrix assessed
in the collagen-induced arthritis mouse model. Int J Low
Extrem Wounds 2018;17:275-81.
12. Yang CK, Polanco TO, Lantis JC 2nd. A prospective, post-
market, compassionate clinical evaluation of a novel acel-
lular fish-skin graft which contains omega-3 fatty acids for
the closure of hard-to-heal lower extremity chronic ulcers.
Wounds 2016;28:112-8.
13. Baldursson BT, Kjartansson H, Konradsdottir F, et al. Heal-
ing rate and autoimmune safety of full-thickness wounds
treated with fish skin acellular dermal matrix versus por-
cine small-intestine submucosa: a noninferiority study. Int
J Low Extrem Wounds 2015;14:37-43.
14. Magnusson S, Baldursson BT, Kjartansson H, et al. Regen-
erative and antibacterial properties of acellular fish skin
grafts and human amnion/chorion membrane: implica-
tions for tissue preservation in combat casualty care. Mil
Med 2017;182:383-8.
15. Pavlovcic U, Diaci J, Mozina J, et al. Wound perimeter,
area, and volume measurement based on laser 3D and col-
or acquisition. Biomed Eng Online 2015;14:39.
16. Rajbhandari SM, Harris ND, Sutton M, et al. Digital imag-
ing: an accurate and easy method of measuring foot ulcers.
Diabet Med 1999;16:339-42.
... To date, piscine acellular dermal matrices have been used successfully across a wide spectrum of pathologies, from burns and traumatic wounds to chronic ulcerations frequently seen in diabetes and venous stasis. 11,12 Baldursson et al. demonstrated in their study that these grafts demonstrated significantly faster healing times compared to their porcine derived counterparts. 13 On a cellular level, the grafts have been shown to be free of risk in terms of adverse autogenic responses as well as viral and bacterial transmission. ...
Article
Full-text available
Background An estimated 84,944 lawn mower injuries occur annually in the United States, of those 16.2% involving the lower extremity.¹ Often, a significant soft tissue deficit is present leaving limited reconstructive options available to the surgeon or wound care provider. Split-thickness skin graft (STSG) has long been considered the mainstay for treatment of large skin defects caused by traumatic wounds. Issues related to graft loss, scar contracture, loss of elasticity, adhesions to tendons and unfavorable aesthetic results are regarded as limitations of skin grafting alone.² As a result, acellular dermal matrices have seen an increase in usage due to their potential to overcome these limitations.
... The basic treatment method used in our hospital is based on the burn treatment method contained in the burn treatment book, 'Total Burn Care' (5th ed.) [11]. Briefly, in the case of an acute burn patient, excess discharge prevents the ADM (acellular dermal matrix) from effectively treating the wound, and hence, 1 ~ 5 days have to be delayed [12]. Additionally, we have treated the donor site once for the reasoning that the natural healing rate is around 2 weeks, thereby, when applied 2-fold, it is difficult to compare and assess the healing rate of various treatment methods [13]. ...
Article
Full-text available
Due to its high polyunsaturated fatty acid content, acellular fish skin has emerged as a dermal substitute for the promotion of wound healing as it decreases scar formation while providing pain relief. However, various systematic studies on acellular fish skin, such as its biophysical analysis, in vitro activities, and clinical application, have not been sufficiently investigated. In this study, we conducted a comparative study to evaluate the wound-healing ability of acellular fish skin graft (Kerecis®) with that of the widely used bovine collagen skin graft (ProHeal®). The skin grafts were evaluated not only in terms of their biophysical properties, but also their in vitro cellular activities, using fibroblasts, keratinocytes, and human endothelial cells. The clinical study evaluated wound healing in 52 patients with acute burns who underwent skin grafting on donor sites from January 2019 to December 2020. The study was conducted with two groups; while only Kerecis® was tested in one group, Kerecis® and ProHeal® were compared in the other. In both groups, the application time of the dressing material was one to two days after split-thickness skin grafting to the donor sites. The Kerecis®-treatment group experienced faster healing than the other treatment group. In particular, the average wound healing time using the Kerecis® treatment and the ProHeal® treatment was 10.7 ± 1.5 days and 13.1 ± 1.4 days, respectively. We believe that the faster healing of the Kerecis® treatment, compared to that of the ProHeal® treatment, maybe due to the synergistic effect of the unique biophysical structure and the bioactive components of acellular fish skin.
Article
Objective To evaluate new medical devices and drugs pertinent to otolaryngology–head and neck surgery that were approved by the Food and Drug Administration (FDA) in 2021. Data Sources Publicly available FDA device and drug approvals from ENT (ear, nose, and throat), anesthesia, neurosurgery, plastic surgery, and general surgery FDA committees. Review Methods FDA device and therapeutic approvals were identified and reviewed by members of the American Academy of Otolaryngology–Head and Neck Surgery’s Medical Devices and Drugs Committee. Two independent reviewers assessed the relevance of devices and drugs to otolaryngologists. Medical devices and drugs were then allocated to their respective subspecialty fields for critical review based on available scientific literature. Conclusions The Medical Devices and Drugs Committee reviewed 1153 devices and 52 novel drugs that received FDA approval in 2021 (67 ENT, 106 anesthesia, 618 general surgery and plastic surgery, 362 neurosurgery). Twenty-three devices and 1 therapeutic agent relevant to otolaryngology were included in the state of the art review. Advances spanned all subspecialties, including over-the-counter hearing aid options in otology, expanding treatment options for rhinitis in rhinology, innovative laser-safe endotracheal tubes in laryngology, novel facial rejuvenation and implant technology in facial plastic surgery, and advances in noninvasive and surgical treatment options for obstructive sleep apnea. Implications for Practice FDA approvals for new technology and pharmaceuticals present new opportunities across subspecialties in otolaryngology. Clinicians’ nuanced understanding of the safety, advantages, and limitations of these innovations ensures ongoing progress in patient care.
Article
Management of wounds is a commonly performed and essential aspect of small animal veterinary medicine. Appropriate wound management is a difficult art to master, due to the inherent complexity of the clinical scenario, as well as the ever-evolving nature of the field with the constant addition of new products and techniques. This article reviews key concepts that may help the practitioner better understand the natural process of wound healing, factors that delay healing and strategies to help improve the local wound environment to make it more conducive to healing during open wound management. The concept of wound bed preparation is defined before common local wound management strategies, such as wound lavage and debridement, are discussed in more detail. Key aspects of the management of biofilms and appropriate use of antimicrobial agents are also reviewed. Finally, the concept of moist wound healing and its impact in modern wound management is explained before a broad variety of types of wound dressings are reviewed, with a particular focus on active dressings.
Article
Full-text available
Methods: Ten patients having split-thickness skin grafting for burn injury were treated with the fish skin xenografts. Results: There were no adverse reactions noted on the use of the fish skin grafts. No patient had any reaction to the fish skin and there was a zero incidence of infection. The handling of the fish skin was excellent, a robust and pliable xenograft that was easy to apply.The quality of donor site healing was judged to be good in all cases. Both the analgesic effect noted and the relatively short average times until 100% re-epithelialization are promising. We also illustrate two cases where the dressing was used to treat superficial burns.
Article
Full-text available
It is vital that cellular- and tissue-based products (CTPs) used for wound treatment do not provoke autoimmunity. In this study, the immunogenic response to extracts of 2 CTPs of piscine and porcine origin was assessed in the collagen-induced arthritis model. Male DBA/1J mice were divided into 4 groups, each composed of 7 to 9 animals. Each animal was injected with one of following to assess their immune responses: (1) bovine type II collagen (100 µg) in Freund's adjuvant, (2) extract of piscine skin (100 µg) in Freund's adjuvant, (3) extract of porcine urinary bladder matrix (100 µg) in Freund's adjuvant, or (4) Freund's adjuvant alone (control) at the beginning of the experiment and 3 weeks later. Clinical signs of arthritis were assessed from week 5 onwards, and anti-type II and anti-type I collagen antibody immunoglobulin G (IgG) serum levels were measured before injections and 8 weeks after exposure using enzyme-linked immunosorbent assays. Only the mice exposed to bovine type II collagen developed clinical arthritis accompanied by very high anti-type II collagen IgG serum levels. Anti-type II collagen IgG serum levels were also detected in the porcine group but were undetectable in the piscine skin and control groups after 8 weeks. There were no significant differences in anti-type I collagen IgG serum levels among the groups. The results showed that piscine skin did not provoke systemic autoimmunity against type II collagens in DBA/1J mice.
Article
Full-text available
Introduction The Kerecis™ Omega3 Wound matrix is a decellularized skin matrix derived from fish skin and represents an innovative concept to achieve wound healing. The aim of this study was to report the cumulative experience of three centers for vascular surgery regarding use of the Omega3 Wound matrix in selected patients with complicated wounds. Material and methods In this study 23 patients with 25 vascular and/or diabetes mellitus-associated complicated wounds and partially exposed bony segments were treated with the Omega3 Wound matrix in three vascular centers. In several patients, conventional wound treatment with vacuum therapy had previously been carried out sometimes over several weeks without durable success. Following initial debridement in the operating room, the matrix was applied and covered with a silicone mesh. In the further course, wound treatment was conducted on an outpatient setting if possible. Results In total 25 wounds were treated with localization at the level of the thigh (n = 2), the distal calf (n = 7), the forefoot (n = 14) and the hand (n = 2). The time to heal varied between 9 and 41 weeks and between 3 and 26 wound matrices were applied per wound. Interestingly, a reduction of analgesics intake was noted when the treatment with the Omega3 Wound matrix was initiated. Conclusion The novel Omega3 Wound matrix in this study represented an effective treatment option in 25 complicated wounds. Further studies are necessary to evaluate the impact of the wound matrix on stimulation of granulation tissue and re-epithelialization as well as the potential antinociceptive and analgetic effects.
Article
Full-text available
Background: Improvised explosive devices and new directed energy weapons are changing warfare injuries from penetrating wounds to large surface area thermal and blast injuries. Acellular fish skin is used for tissue repair and during manufacturing subjected to gentle processing compared to biologic materials derived from mammals. This is due to the absence of viral and prion disease transmission risk, preserving natural structure and composition of the fish skin graft. Objectives: The aim of this study was to assess properties of acellular fish skin relevant for severe battlefield injuries and to compare those properties with those of dehydrated human amnion/chorion membrane. Methods: We evaluated cell ingrowth capabilities of the biological materials with microscopy techniques. Bacterial barrier properties were tested with a 2-chamber model. Results: The microstructure of the acellular fish skin is highly porous, whereas the microstructure of dehydrated human amnion/chorion membrane is mostly nonporous. The fish skin grafts show superior ability to support 3-dimensional ingrowth of cells compared to dehydrated human amnion/chorion membrane (p < 0.0001) and the fish skin is a bacterial barrier for 24 to 48 hours. Conclusion: The unique biomechanical properties of the acellular fish skin graft make it ideal to be used as a conformal cover for severe trauma and burn wounds in the battlefield.
Article
Full-text available
Wound measuring serves medical personnel as a tool to assess the effectiveness of a therapy and predict its outcome. Clinically used methods vary from measuring using rules and calipers to sophisticated methods, based on 3D measuring. Our method combines the added value of 3D measuring and well-known segmentation algorithms to enable volume calculation and achieve reliable and operator-independent analysis, as we demonstrate in the paper. Developed 3D measuring system is based on laser triangulation with simultaneous color acquisition. Wound shape analysis is based on the edge-determination, virtual healthy skin approximation over the wound and perimeter, area, and volume calculation. In order to validate the approach, eight operators analyzed four different wounds using proposed method. Measuring bias was assessed by comparing measured values with expected values on an artificially modeled set of wounds. Results indicate that the perimeter, area, and volume are measured with a repeatability of 2.5 mm, 12 mm(2), and 30 mm(3), respectively, and with a measuring bias of -0.2 mm, -8.6 mm(2), 24 mm(3), respectively. According to the results of verification and the fact that typical wound analysis takes 20 seconds, the method for wound shape measurement can be clinically used as a precise tool for objectively monitoring the wound healing based on measuring its 3D shape and color.
Article
Full-text available
Wound measurement is an objective and direct way to trace the course of wound healing and to evaluate therapeutic efficacy. Nevertheless, the accuracy and efficiency of the current measurement methods need to be improved. Taking the advantages of reliability of transparency tracing and the accuracy of computer-aided digital imaging, a transparency-based digital imaging approach is established, by which data from 340 wound tracing were collected from 6 experimental groups (8 rats/group) at 8 experimental time points (Day 1, 3, 5, 7, 10, 12, 14 and 16) and orderly archived onto a transparency model sheet. This sheet was scanned and its image was saved in JPG form. Since a set of standard area units from 1 mm(2) to 1 cm(2) was integrated into the sheet, the tracing areas in JPG image were measured directly, using the "Magnetic lasso tool" in Adobe Photoshop program. The pixel values/PVs of individual outlined regions were obtained and recorded in an average speed of 27 second/region. All PV data were saved in an excel form and their corresponding areas were calculated simultaneously by the formula of Y (PV of the outlined region)/X (PV of standard area unit) × Z (area of standard unit). It took a researcher less than 3 hours to finish area calculation of 340 regions. In contrast, over 3 hours were expended by three skillful researchers to accomplish the above work with traditional transparency-based method. Moreover, unlike the results obtained traditionally, little variation was found among the data calculated by different persons and the standard area units in different sizes and shapes. Given its accurate, reproductive and efficient properties, this transparency-based digital imaging approach would be of significant values in basic wound healing research and clinical practice.
Chapter
The advantageous biocompatibility and cell proliferative effects of synthetic and natural biomaterials have promoted their broad use in various medical areas, including wound healing. Most synthetic biomaterials show excellent physical properties but are, in general, complicated to fabricate, whereas natural biomaterials normally show no cell toxicity or elicit foreign body responses but show high natural variability. This chapter gives an overview of existent biomaterials used for wound healing purposes, especially the naturally obtained categories such as polysaccharide-based, protein-based, nanofiber-based, and marine biomaterials, which have been investigated in depth in vivo and in clinical studies. The potentials, but also the limitations, of novel biomaterials for wound healing applications are also discussed.
Article
Introduction: A novel piscine acellular fish-skin graft product has 510k clearance on the US market. This product (Omega3, Kerecis, Isafjordur, Iceland) is to be used similarly to extracellular matrices (ECMs) on the market (eg, bovine and porcine) except that it contains fats, including omega-3 polyunsaturated fatty acids that have been associated with anti-inflammatory properties in many studies. While many current ECMs are effective on open wounds, studies have largely excluded application to hard-to-heal ulcers. To test this product in a real-world environment, the authors chose to look specifically at hard-to-heal ulcers based on previously defined wound and patient factors. Methods: The primary objective was to assess the percentage of wound closure area from baseline after 5 weekly fish-skin graft applications in 18 patients with at least 1 "hard-to-heal" criteria. Patients underwent application of the fish skin for 5 sequential weeks, followed by 3 weeks of standard of care. Wound area, skin assessments, and pain were assessed weekly. Results: A 40% decrease in wound surface area (P < 0.05) and a 48% decrease in wound depth was seen with 5 weekly applications of the fish-skin graft and secondary dressing (P < 0.05). Complete closure was seen in 3 of 18 patients by the end of the study phase. Conclusion: This fish-skin product appears to provide promise as an effective wound closing adjunctive ECM. This is true when used in this compassionate setting, where many other products fail. This study lacks a control arm and an aggressive application schedule, but the investigators believe it represents real-world practice.
Article
A novel product, the fish skin acellular dermal matrix (ADM) has recently been introduced into the family of biological materials for the treatment of wounds. Hitherto, these products have been produced from the organs of livestock. A noninferiority test was used to compare the effect of fish skin ADM against porcine small-intestine submucosa extracellular matrix in the healing of 162 full-thickness 4-mm wounds on the forearm of 81 volunteers. The fish skin product was noninferior at the primary end point, healing at 28 days. Furthermore, the wounds treated with fish skin acellular matrix healed significantly faster. These results might give the fish skin ADM an advantage because of its environmental neutrality when compared with livestock-derived products. The study results on these acute full-thickness wounds might apply for diabetic foot ulcers and other chronic full-thickness wounds, and the shorter healing time for the fish skin-treated group could influence treatment decisions. To test the autoimmune reactivity of the fish skin, the participants were tested with the following ELISA (enzyme-linked immunosorbent assay) tests: RF, ANA, ENA, anti ds-DNA, ANCA, anti-CCP, and anticollagen I and II. These showed no reactivity. The results demonstrate the claims of safety and efficacy of fish skin ADM for wound care. © The Author(s) 2015.
Article
The determination of healing rate in the diabetic foot wound is an important assessment parameter that is part of the overall clinical decision-making process in wound treatment. A number of methods that have been used to calculate healing, ranging from length and width measurement, surface area measure changes expressed as a function of time and linear advancement of the wound edge. The objective of this study was to compare surface area measures to linear advancement of the wound edge in 228 diabetic foot ulcers. Each wound was measured using the two methods and analyzed using linear regression to determine the best modeling of the healing process in these wounds. Results indicated that the total surface area change per day was superior to the linear advancement parameter in this group of wounds and that the area measurement was significantly more likely to predict the healing trajectory in the subgroup of wounds that took more than 28 days to heal. Contrary to expectations, the linear advancement method was correlated to initial wound size in the longer duration wounds suggesting that in these chronic wounds, differing healing phases render the surface area calculation method superior to the linear advancement parameter.