The Use of Cadaveric Skin Allografts in the Management of Extensive Wounds

Abstract

Skin grafting is a major element in the management of extensive wounds. Although the permanent closure of extensive wounds using autologous skin grafts is the gold standard, this scenario is rarely feasible due to the limited availability of autograft skin in these patients. Hence, biological or synthetic skin substitutes are necessary for the temporary coverage of massive wounds. Among these, cadaveric skin allografts remain the first choice due to their numerous advantages. They reduce the loss of water, proteins and electrolytes, improve thermoregulation, reduce pain and lower the risk of wound infection. Furthermore, they improve subsequent autograft take by stimulating epithelization and preparing the wound bed. Prompt excision of massive burn wounds and temporary coverage with allograft skin significantly reduces mortality and shortens hospitalization. Future research must address the current disadvantages associated with the use of allograft skin, mainly the limited availability, high antigenicity, risk of infection transmission, as well as optimization of the processing and storage techniques.

Full text

FORENSIC PATHOLOGY
Rom J Leg Med [29] 37-44 [2021]
DOI: 10.4323/rjlm.2021.37
© 2021 Romanian Society of Legal Medicine
37
THE USE OF CADAVERIC SKIN ALLOGRAFTS IN THE MANAGEMENT OF EXTENSIVE
WOUNDS
Liliana Gabriela Popa1,2, Calin Giurcaneanu1,2, Mara Madalina Mihai1,2,3, *, Cristina Beiu2, Olguta Anca Orzan1,2,
Sivius Negoita4,5, Marian Burcea6, Ruxandra Ioana Turlea7, Catalin Ionel Enachescu1
1Elias Emergency University Hospital, Department of Dermatology, 2“Carol Davila” University of Medicine and
Pharmacy, Department of Oncologic Dermatology, 3Research Institute of the University of Bucharest (ICUB),4“Elias”
Emergency University Hospital, Department of Anaesthesiology and Intensive Care, 5“Carol Davila” University of
Medicine and Pharmacy, Department of Anaesthesiology and Intensive Care, 6“Carol Davila University of Medicine
and Pharmacy, Clinical Hospital for Ophtalmological Emergencies Bucharest, Department of Ophtalmology, 7“Mina
Minovici” National Institute of Legal Medicine, Bucharest, Romania
Abstract: Skin graing is a major element in the management of extensive wounds. Although the permanent
closure of extensive wounds using autologous skin gras is the gold standard, this scenario is rarely feasible due to the limited
availability of autogra skin in these patients. Hence, biological or synthetic skin substitutes are necessary for the temporary
coverage of massive wounds. Among these, cadaveric skin allogras remain the rst choice due to their numerous advantages.
ey reduce the loss of water, proteins and electrolytes, improve thermoregulation, reduce pain and lower the risk of wound
infection. Furthermore, they improve subsequent autogra take by stimulating epithelization and preparing the wound bed.
Prompt excision of massive burn wounds and temporary coverage with allogra skin signicantly reduces mortality and
shortens hospitalization.
Future research must address the current disadvantages associated with the use of allogra skin, mainly the limited
availability, high antigenicity, risk of infection transmission, as well as optimization of the processing and storage techniques.
Keywords: cadaveric, skin, allogra, burn.
*Correspondence to: Mara Madalina Mihai, MD, PhD, Assistant Professor, No.17 Marasti Bd, District 1, Bucharest, Romania, E-mail:
mara.mihai@umfcd.ro
INTRODUCTION
e continuity of the integument is crucial
for the protection of the body. erefore, early wound
excision or debridement and skin replacement in patients
with extensive burns, traumatic cutaneous denudations
or exfoliative skin diseases are major determinants
for reducing morbidity and improving survival. Skin
graing is the pivotal element in the management of
extensive wounds. Although the permanent closure
of extensive wounds using autologous skin gras is
the gold standard, this scenario is rarely feasible due
to the limited availability of autogra skin in these
patients. Hence, biological or synthetic skin substitutes
are necessary for the temporary coverage of massive
wounds.
Among these, fresh or cryopreserved cadaveric
skin allogras represent the best option given their
availability, low cost and ability to quickly revascularize.
eir content of viable epidermal and dermal cells is of
utmost importance. It has been shown that the dermal
noncellular constituents of such allogras are passed to
the wound bed and the cells release a series of growth
factors and cytokines, creating a local environment that
favors the growth of keratinocytes and skin renewal
[1]. Non-viable allogras such as glycerolized, gamma
irradiated, freeze dried or ethylene oxide - treated
allogras may also be used. Xenogras, primarily
porcine skin gras are rarely employed for the temporary
dressing of extensive wounds as they do not revascularize.
As expected, the antigenic incompatibility leads to the
rejection of allogras and xenogras.
Skin substitutes, like in vitro cultured epidermal
autogras or dermal substitutes consisting of a collagen
1300

Popa L.G. et al.
38
and glycosaminoglycans matrix are successfully used
for extensive wound coverage, but are rarely the rst
choice due to their high cost [2]. Another drawback for
skin substitutes is their content of either epidermal or
dermal components, seldom both. While the rst are
associated with reduced elasticity and plasticity given
the absence of dermal constituents, the later require the
growth of a new epidermis over the wound, which takes
place over extended periods of time [2]. In addition, skin
substitutes are very frail and sensitive to shear stress,
therefore the management of wounds covered with
skin substitutes is very demanding [3,4]. Bioengineered
skin substitutes, composed of a bovine collagen and
glycosaminoglycans matrix covered by a silicone sheet
that serves as an epidermis have been developed, but
they are very expensive and need further research [5].
Another promising product is represented
by a suspension of autologous cells (keratinocytes,
broblasts, melanocytes) that is sprayed over the
wounds. e suspension is obtained by performing a
dermal-epidermal junction biopsy [2].
Nevertheless, cadaveric allogras remain the
top choice for temporary coverage not only of extensive
wounds, but also non-healing chronic wounds such as
decubitus ulcers, diabetic foot wounds or venous leg
ulcers.
HISTORY OF THE USE OF CADAVERIC SKIN
ALLOGRAFTS
During the past decades deceased donor
skin allogras have been widely used as a temporary
dressing for extensive wounds, especially massive
burns. In the course of time, the technological advances,
the development of skin banking and the clarication
of the legislation regarding tissue banking led to great
progress in the eld [6].
Bert was the rst to assert, in 1863, that gra
survival is conditioned by neovascularization [7].
Shortly aer the description of skin autograing
by Reverdin, in 1871, the use of skin allogras was
endorsed. In 1874, iersch reported the use of partial-
thickness gras for wound coverage in a series of
patients. However, these very thin epidermal gras,
referred to as “iersch gras” or “pinch-gras” only
yielded satisfactory results in small wounds. Before
long, the importance of the dermal components of skin
gras for their successful use in larger wounds became
obvious. In 1886, iersch published the manuscript
entitled “On skin graing”, laying the foundation for
the use of split-thickness skin gras [7,8].
Although human skin banking started in
the early 1900s it was not until 1938 that refrigerated
cadaveric skin allogras were used to cover extensive
full-thickness burns [8]. However, the high rates
of allogra rejection and inadequate methods of
preservation represented serious challenges. Research
aiming the long term maintenance of human allogra
skin viability followed and in 1952, Billingham and
Medawar reported successful cryopreservation of
skin allogras using glycerol [8]. Cadaveric allogra
skin soon became the preferred biologic dressing not
only in patients with extensive bruns, but also in those
with non-healing skin ulcers, traumatic wounds and
even chronic infected wounds owing to its potential to
reduce bacterial colonization and proliferation and to
stimulate neovascularization [8]. us, during the last
few decades, numerous skin banks have been founded
throughout the world, most of them in the close vicinity
of regional burn centers.
Professor Agrippa Ionescu was the rst
physician to perform skin transplant in an organized
hospital setting in Romania, in 1958. e use of skin
allogras is regulated by Law No.95/2006 concerning
the removal and the transplant of human organs,
tissues and cells for therapeutical propose, which is in
agreement with the Europe an legislation. Unfortunately,
the only skin bank in Romania, founded in “Grigore
Alexandrescu” Hospital, Bucharest was closed by the
authorities in 2018, aer 22 years of activity, due to the
lack of infrastructure, human and nancial resources.
PRELEVATION AND PREPARATION OF SKIN
ALLOGRAFTS
Donor screening
Obtaining the medical history of the donor,
performing a detailed skin examination and screening
for infections [human immunodeciency virus (HIV)
1/2, hepatitis B virus (HBV), hepatitis C virus (HCV),
human T cell lymphotropic virus (HTLV)-1, syphilis,
cytomegalovirus (CMV)] and cutaneous bacterial
contamination are mandatory.
Skin retrieval
e interval between the time of death and skin
collection, as well as the body storage conditions should
be well documented. According to current guidelines, to
ensure viability, the cutaneous gras ought to be removed
within 24h postmortem if the donor body is refrigerated
during the rst 12h of asystole and within 15h aer
the donor’s death if the donor body is not refrigerated
P<0.05 is considered as signicant

e Use of Cadaveric Skin Allogras in the Management of Extensive Wounds
39
[8]. In addition, skin processing at room temperature
(25°C) before hypothermic storage is associated with
degradation of the dermis. erefore, it is advisable
that aer retrieval the skin be placed immediately into
nutrient tissue culture medium maintained at 4°C on
wet ice, transported and held at this temperature till
packaging and hypothermic storage [8].
e procedure is performed under aseptic
conditions, in a sterile operating room. e donor
areas are usually the torso, buttocks, and the lower
limbs in order not to alter the appearance of the donor’s
exposed areas in an open con. Areas aected by
skin diseases, skin cancer, connective tissue disorders,
areas covered with tattoos, those that display burn or
traumatic injuries or signs of infections are excluded for
skin donation [9]. e selected donor areas are shaved,
thoroughly disinfected and covered with a ne layer
of sterile paran oil or another lubricant that reduces
resistance and facilitates skin removal. An electric
dermatome is then used to obtain split-thickness skin
gras 0.03- 0.045 cm thick and 7.5-10 cm wide [8].
Generally, an average of 0.5 m2 of skin is collected form
one donor. e skin gras are transported in tissue
culture medium [primarily Eagle’s Minimal Essential
Medium (EMEM), but also Dulbecco’s Modied Eagle
Medium (DMEM) or RPMI-1640] kept at temperatures
of 1-10°C in insulated containers to the skin bank, where
they are processed [10]. e addition of antibiotics to
the transport medium is controversial, as their action is
impaired by the low temperature and this may lead to
the development of resistant microorganisms. It has not
yet been settled which antibiotics are most eective and
less toxic for the autogras’ cellular components [8].
Skin samples not exposed to antibiotics
obtained from dierent harvesting areas are sent for
microbiological assays, including cultures for aerobic
and anaerobic bacteria, yeast, and fungi.
Skin processing and storage
Skin processing is also performed in an
aseptic manner. e skin samples ought to be carefully
maneuvered in order to reduce tissue deterioration.
ey are cleansed with antiseptic solutions (0.025%
sodium hypochlorite mixed in phosphate buer saline)
that remove the surplus of lubricants and dead skin cells,
transferred into sterile containers with nutrient storage
medium (especially ΕΜΕΜ with 10% fetal bovine serum
or pooled human sera) with or without antibiotics
(usually amikacin, amoxicillin and vancomycin) and
antifungals (amphotericin B) and refrigerated at 4°C
as fresh skin allogras [11,12]. ese are the preferred
temporary biologic dressing for extensive wounds
given their rapid adherence and revascularization. If
not used in 5-7 days, refrigerated skin allogras must
undergo cryopreservation. However, it has been shown
that cellular viability can be maintained for 10 - 14
days at 4°C provided the medium is changed every 3
days [8]. In case the medium cannot be changed at the
mentioned rate, the gras ought to be preserved within
96h of retrieval [13].
Skin allogras that need long term storage are
meshed and incubated in a cryoprotectant solution
(generally 10-15% glycerol or 10% dimethylsulphoxide)
for 30 minutes at 4°C to reduce cryogenic cellular
damage [8,11]. Postprocessing skin samples are also
sent for microbiological testing. Skin allogras are then
packed in thin, at pouches to ensure uniform freezing,
sealed and submitted to a controlled-rate freezing
of -1°C/min to -70 - -100°C [8,11]. Aerwards, they
are placed in a mechanical freezer (-70 to -100°C) or
in vapor-phase (-130°C) or liquid nitrogen (-196°C)
[8,9]. is way, 85% of the cellular viability of the
skin allogras is maintained [8]. e viability of skin
allogras is preserved for 3 - 6 months in mechanical
freezers and up to 10 years in liquid nitrogen [8].
Another method of skin preservation is
incubation in 85% glycerol. As a consequence, free
water is xed in the intra and extracellular spaces.
Glycerolization is preferred by some skin banks given
the much lower costs and ease of production, storage
and distribution compared to cryopreservation, the
possibility to preserve such samples up to 5 years,
along with its antibacterial and antiviral eects, as
well as the reduced antigenicity of glycerol preserved
skin allogras [12,14,15]. However, the later show
more pronounced mechanical and structural changes
and destruction of skin cells, are more rigid and less
expandable than cryopreserved allogras [16,17].
As research on the optimal way to preserve
allogra skin continues, new methods have been
studied, including the use of highly concentrated
propylene glycol [18] or disinfection with peracetic
acid and preservation in glycerol [19], but further
investigations are needed.
Rewarming of cryopreserved allogra skin
Frozen storage packets are transported on dry
ice in insulated containers as skin temperature should
not rise above -50°C [8]. Before utilization, warming
is carried out over 2 - 4 minutes at a temperature of
10 - 37°C. A rewarming rate of 127 - 470°C /min is
recommended in order to minimize cryodamage [8].

Popa L.G. et al.
40
CLINICAL USES AND TECHNIQUES
e successful engrament of extensive
wounds is conditioned by an adequate preparation of
the wound bed. Necrotic tissue should be promptly
excised in order to prevent wound infection, lower
the risk of gra rejection, prevent signicant scarring
and contracture and hasten recovery [2]. In the case
of mid dermal wounds, gradual tangential excision
is performed down to healthy tissue, which is easily
recognized by the presence of diuse punctate bleeding
indicative of a viable dermal plexus [2,7]. In deeper
wounds, tangential or fascial excision is required.
Apart from the necrotic debris, the granulation tissue
must also be removed to prevent infection and increase
gra adherence [2]. Once proper debridement and
meticulous haemostasis are completed, the allogra
is placed on the wound and xed by suture material,
brin glue, tissue glue or staples [7].
e use of cadaveric allogras for the
temporary closure of extensive wounds has numerous
advantages. ese allogras are physiological barriers
that contain both epidermis and dermis. erefore,
they reduce the loss of water, proteins, electrolytes, as
well as heat, preventing wound desiccation, improving
thermoregulation and ameliorating the patient’s general
condition and nutritional status [8,20]. ey also reduce
pain, lower the risk of wound infection and suppress
bacterial proliferation in contaminated wounds [15].
Furthermore, by the transfer of the allogra’s dermal
elements to the wound bed, they facilitate healing and
enhance the function the denitive gra and the quality
of the scar [21]. Temporary wound coverage with
allogras also reduces later autogra requirement and
improves autogra take as it stimulates epithelization
and prepares the wound bed [20]. Numerous studies
concluded that prompt excision of massive burn
wounds and temporary coverage with allogra skin
signicantly reduces mortality and shortens hospital
stay [11,22].
e temporary coverage of extensive full-
thickness wounds
In patients with extensive full-thickness
wounds, the best results are achieved when skin
allogras are applied unmeshed. Fresh allogras are
superior for temporary wound closure to cryopreserved
gras as they revascularize faster, adhere better to the
wound bed, and tolerate minor bacterial contamination
of the wound [23]. Glycerol preserved allogras are less
adherent to the wound bed than fresh and cr yopreser ved
skin allogras [7].
Meshing of fresh skin allogras is not
recommended for the coverage of full thickness
wounds as reepithelialization of the interstices with
allogenic epidermis doesn’t usually take place [8].
Nevertheless, when wounds cover ≥ 50% of the body,
meshed allogras at various expansion rates (3:1, 4:1 or
6:1) may be applied [9].
Shearing of the allogra must be prevented
as it impedes gra take and neovascularization [2].
e allograed wound is covered with a non-adherent
dressing. e use of negative pressure wound therapy
is recommended. It immobilizes the gra, minimizes
shearing and also draws out all excessive uid from
under the allogra [2]. Otherwise, the uid build-up
under the allogra prevents its uniform adhesion to the
wound bed and may lead to gra failure.
Removal of the allogeneic skin is performed as
soon as permanent wound coverage with autologous
skin is practicable.
Apart from massive burns, other deep
wounds, like pyoderma gangrenosum, a rare disorder
usually associated with inammatory bowel disease
or hematologic conditions, that may also arise as a
postoperative complication [24] and those encountered
in patients with meningococcemia or purpura
fulminans have been successfully covered with allogra
skin once the patients were able to tolerate surgery
[25]. Persistent post-traumatic or surgical wounds
are also amenable to allograing. e risk of chronic,
non-healing postoperative cutaneous defects is greatly
diminished in laparoscopic surgery [26,27].
Deep, long-standing leg ulcers refractory to
other treatments represent another indication for
allogeneic skin graing. Although coverage of such
leg ulcers with autologous split-thickness gras is the
gold standard, they may not succeed in full thickness
ulcers as they only contain supercial parts of the
dermis [21]. e dermis does not possess renewal
potential [25]. erefore, the use of allogras or de-
epidermized dermis (DED) has proven very helpful as
these biomaterials assist the restoration of the dermis.
As mentioned previously, their collagen and elastic
bers are passed to the wound bed, creating a scaold
that is subsequently inltrated by host cells, mainly
myobroblasts that remodel the gra’s extracellular
matrix (ECM) [26-28]. Capillaries of the wound bed
also invade the ECM [21]. us, the allogra intimately
adheres to the wound bed. Moreover, viable cells within
the allogra release growth factors and cytokines
that promote healing. In approximately 4 weeks, due
Figure 1. Light microscopic micrograph of testis in control group.

e Use of Cadaveric Skin Allogras in the Management of Extensive Wounds
41
to vascularization and active ECM remodeling, the
allogra is replaced by granulation tissue [21].
In patients with deeper wounds with tendon
or bone exposure, meshed glycerolized or lyophilized
allodermis covered with skin allogras may be used [9].
e “sandwich technique” for the coverage of
extensive full-thickness wounds
In patients in whom the coverage of extensive
wounds can be achieved by a widely meshed autogra,
a “sandwich technique” is commonly used to improve
and accelerate healing. is technique, described in
1981 by Alexander et al. consists in the application of an
unmeshed allogra over the over-expanded autogra,
thus ensuring protection of the later against mechanic
factors, desiccation and infection. As reepithelization of
the interstices by autologous epithelium is completed,
separation of the allogra from the wound bed takes
place [7]. However, sometimes the allogra causes
an inammatory rejection reaction which impedes
reepithelialisation. is may be avoided by the use of
less antigenic biologic products, such as lyophilized
skin allogras or acellular dermal matrices [8,9].
Temporary coverage of extensive partial-
thickness wounds
Several authors advocate the use of meshed or
unmeshed cadaveric skin allogras for the temporary
coverage of extensive partial-thickness wounds to
hasten reepithelialization and shorten hospitalization
[29].
Patients with exfoliative dermatoses like
Stevens-Johnson syndrome/toxic epidermal necrolysis
or staphylococcal scalded skin syndrome greatly benet
from the use of allogra skin for the temporar y coverage
of their extensive wounds pending spontaneous
reepithelialization [30,31].
Predicting and promoting subsequent
autologous gra acceptance
Early coverage of the debrided wound bed with
an allogra does not only oer protection, but also
promotes neovas cularizat ion [32]. e integration of the
allogeneic skin gra reects the suitability of the wound
bed and the existence of an optimal blood supply that
will ensure successful subsequent autograing [33].
e combined use of allogeneic and autologous
biomaterials
An interesting approach is the use of allogeneic
dermis or an acellular dermal matrix with cultured
epidermal autogras or thin autogras [8].
Reports on the use of microgras of both
autologous and allogeneic skin have been published
[34]. Autogras smaller than 1 mm are seeded on the
dermal surface of large sheets of allogra skin that are
consequently applied on the wound. Reepithelization
occurs due to the spread of the autologous keratinocytes,
while the allogra skin progressively separates from the
wound bed. Nevertheless, this micrograing method is
associated with important wound contraction [34].
Use of allogenic skin gras in ophthalmology
Jacques-Louis Reverdin (1842-1929) was the
rst surgeon to experiment the allogra full thickness
skin gra (FTSG) in 1869 [35, 36]. Aer 1869-1874
at his recommendation the use in ophthalmology for
healing of small wounds is very much applied especially
in palpebral surgery. While skin gra use in surgery
is sporadic, the use in ophthalmology has a lot of
beneces. FTSG continue to improve aer surgery i.e.
in facial nerve palsy and this is to be taken into account
before a nal forensic evaluation [37]. Even today skin
gra in ophthalmology is highly recommendate for
surgical treatment of ectropion to allow full closure of
the eye lid and further on corneal lesions [38].
Skin gra in ophthalmology may have many
other applications such as skin actinic lesions, etc. [39]
skin gras and lens transplantation in ophthalmology
is a reparatory domain professional interesting and
challenged but also with large social utilities and
sustain the progress of modern medicine in improving
the quality of life.
Conclusion. e use of periocular FTSG is
eective in improving lagophthalmos and periorbital
symmetry in patients with FNP
CHALLENGES ASSOCIATED WITH THE USE OF
CADAVERIC ALLOGRAFT SKIN
Limited availability and medico-legal issues
e principal issue that restricts the use of
cadaveric allogra skin is its limited availability. All
over the world, the tissue donor rate does not meet
demands and in some countries it is alarmingly low due
to lack of resources, logistics problems, but also social
and cultural reasons.
Pathologists and forensic pathologists perform
sampling for diagnostic purposes during forensic
autopsies and this is covered by the law enforcement
request. It is a condition sine qua non for a proper
autopsy [40].

Popa L.G. et al.
42
An important aspect is represented by the
organ donation impact on determination of cause of
death. Sometimes, there is a problem between organ/
tissue donation and forensic processes. Depending on
the death circumstances, the forensic pathologist –
requested by law enforcement - examines the body and
the medical documentation provided by the hospital
sta and then consents to donation [52].
Risk of transmission of infectious agents
Transmission of blood borne viruses through
allogra skin has been reported. Nowadays, this risk is
negligible due to strict adherence to protocols.
Another issue is the risk of contamination of
skin allogras with pathogenic bacteria or fungi, which
may generate not only wound infection, but also sepsis
considering the immunocompromised status of the
patients in need of these allogras. As discussed above,
measures to minimize the risk of allogra contamination
are taken throughout the whole process, from the
harvesting, transport, to the processing and storage of
skin allogras. Moreover, microbiological tests are run
aer every phase of the process. If contamination with
pathogenic microorganisms is detected at any moment,
the allogra ought to be discarded [41]. Nonetheless,
according to current guidelines the use of allogra
skin that presents a low bioburden of non-pathogenic
microorganisms is accepted aer a thorough risk
assessment [42].
Allogra rejection
Another drawback in the use of cryopreserved
allogra skin is its rejection, which generally occurs aer
2 - 3 weeks. is is explained by the high antigenicity of
such allogras. eir epidermis contains Langerhans
cells expressing class II major histocompatibility
complex antigens that trigger an immunologic rejection
response [8]. Attempts to reduce antigen presentation
by allogra exposure to ultraviolet radiation or
incubation in glucocorticoids did not prove ecient
in preventing rejection. Improved allogra survival
in patients with extensive burns was reported with
the administration of immunosuppresive agents like
azathioprine, antithymocyte globulin, and cyclosporin
A, but further studies are needed [8].
Lyophilized skin gras, on the other hand, do
not induce an immunologic reaction and survive longer,
but are nally rejected as a result of wound healing [43].
Ethical considerations
Autopsy and forensic autopsy moreover is
known to complete the knowledge and to help the
truth to prevail. is was declared even from 1594
when the famous aphorism of Girolamo Fabricius
Acquapendente known as the father of embryology was
expressed at the University of Padua, “Hic locus est ubi
mors gaudet succurrere vitae” [44].
Cadaveric transplantation included kidney in
1962, liver in 1966, heart in 1967, heart-lung in 1981,
articial heart in 1982, heart xenotransplantation in
1986, split liver in 1996, and rst culture of human
embryonic stem cells in 2000.
e primary ethical dilemmas surrounding
organ transplantation from cadavers [45] arise from the
shortage of available organs [46].
Using access on www.unos.org gives an idea
of the extent of the organ shortage (nearly 20 years
ago):”106 people are added to the nation’s organ
transplant waiting list each day--one every 14 minutes”,
“On average, 68 people receive transplants every day
from either a living or deceased donor”, “On average,
17 patients die every day while awaiting an organ -- one
person every 85 minutes” [47].
e concept of distributive justice rather
many ways a person could justify giving an organ to
one 30 particular individual over someone else. One
distributive justice criteria is equal access: criteria
include length of time waiting (i.e. rst come, rst
served) and age (i.e. youngest to oldest). Some argue to
have this concept free of medical or social worthiness
biases others depriving people who, “have no control
over their need,” of necessary treatment [48].
A second type of distributive justice criteria is
maximum benet with criteria such as medical need (i.e.
the sickest people are prioritised) and best prognosis of
a transplant (i.e. giving organs to the person who has the
best prognosis -life years gained, stressing out the best
medical outcome success probability [49,50], which in
turn has counter arguments in not available scenarios for
best prognosis in advance, bias and favoritism, and life
years criteria is only quantitative giving no equal chances.
Today UNOS [46] encourages in USA transplant
centers to consider as moral criteria: 1) medical need;
2) probability of success, and; 3) time on the waiting
list 43. Not everyone believes in the need to increase
the number of organ transplants because induce the
concept of instrumentalization of the person.
e secondary ethical dilemmas surrounding
organ transplantation in cadaveric donation [44] arises
from donor organs, i.e how to increase the number of
donor organs (organ farming or premature declarations
of death in order to harvest organs are among the public

e Use of Cadaveric Skin Allogras in the Management of Extensive Wounds
43
highest fears).
No transplantation or skin grating is allowed
except from brain death donors (heart beating
cadavers). Strategies to increase cadaveric organ
donations are: education, mandated choice and a free
choice before death, presumed consent (person civic
duty vs. instrumentalization of the body organs as
a social property), incentives (gratitude incentives,
memorial plaque, etc. vs. payment -altruistic need
is morally mandatory), prisoners (death penalty is
unlawful in Europe).
A person becomes a cadaveric organ donor
aer they die and indicating that they would like to
donate either in Transplantation Register or in a will
or by next of kin approval upon request. Skin graing
for individual use of another person is to be granted by
approval on request as in any transplantation activity.
Even if the patient is a registered donor the next of kin
consent is required. In turn if the deceased is registered
in the Transplantation Register this may be considered
a last will no matter the next of kin will [51].
According to Romanian law, the consent
of the family of a deceased person is mandatory for
organ/tissue donation. e rate of organ harvesting
is low because of many factors like organizational
particularities, restrictive criteria for brain death
declaration and, the most important – the mandatory
need for relatives approval [53].
An important problem is represented by a
high prevalence of comorbidities such as hypertension,
diabetes, hepatitis B and C in minority groups. People
from racial minorities are disproportionally represented
on transplant waiting lists [54].
In conclusion, prompt wound excision or
debridement, followed by temporary application of
allogeneic skin gras has proven life-saving in patients
with extensive wounds in whom autogra availability
is extremely limited. Despite the development of new
engineered skin substitutes, the reestablishment of a
skin bank in Romania is an urgent need as the use of
deceased donor allogra skin as temporary biological
wound dressing represents a major element in the
successful management of patients with severe burns.
Future research must address the current disadvantages
associated with the use of allogra skin, mainly the
limited supply, high antigenicity, risk of infection
transmission, as well as optimization of the processing
and storage techniques.
Conict of interest
e authors declare that they have no conict of
interest.
Funding
is work was supported by a grant of the Ministry
of Research, Innovation and Digitization, CNCS/CCCDI –
UEFISCDI, project number PN-III-P1-1.1-PD-2019-1225,
within PNCDI III.
References
1. See P, Phan TT, Chua JJ, Song C, Tan KC, Lee ST. Our Clinical
Experience using Cryopreserved Cadaveric Allogra for the
Management of Severe Burns. Cell Tissue Bank. 2001;2(2):113-117.
2. Elseth A, Nunez Lopez O. Wound Gras. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2020 Jan, Accessed 2021
Jan 20.
3. Sood R, Roggy D, Zieger M, Balledux J, Chaudhari S, Koumanis
DJ, Mir HS, Cohen A, Knipe C, Gabehart K, Coleman JJ. Cultured
epithelial autogras for coverage of large burn wounds in eighty-
eight patients: the Indiana University experience. J Burn Care Res.
2010;31(4):559-568.
4. Haddad AG, Giatsidis G, Orgill DP, Halvorson EG. Skin
Substitutes and Bioscaolds: Temporary and Permanent Coverage.
Clin Plast Surg. 2017;44(3):627-634.
5. Heimbach DM, Warden GD, Luterman A, Jordan MH, Ozobia
N, Ryan CM, Voigt DW, Hickerson WL, Sae JR, DeClement FA,
Sheridan RL, Dimick AR. Multicenter postapproval clinical trial of
Integra dermal regeneration template for burn treatment. J Burn
Care Rehabil. 2003;24(1):42-48.
6. Keswani SM, Mishra MG, Karnik S, Dutta S, Mishra M, Panda S,
Varghese R, Virkar T, Upendran V. Skin banking at a regional burns
centre-e way forward. Burns. 2018;44(4):870-876.
7. Leon-Villapalos J, Eldardiri M, Dziewulski P. e use of human
deceased donor skin allogra in burn care. Cell Tissue Bank.
2010;11(1):99-104.
8. Kagan RJ, Robb EC, Plessinger RT. Human skin banking. Clin
Lab Med. 2005;25(3):587-605.
9. Tognetti L, Pianigiani E, Ierardi F, Mariotti G, Perotti R, Di
Lonardo A, Rubegni P, Fimiani M. Current insights into skin
banking: storage, preservation and clinical importance of skin
allogras. Journal of Biorepository Science for Applied Medicine.
2017;5:41-56.
10. Holder IA, Robb E, Kagan R. Antimicrobial mixtures used to
store harvested skin: antimicrobial activities tested at refrigerator (4
degrees C) temperatures. J Burn Care Rehabil. 1999;20(6):501-504.
11. Chua A, Song C, Chai A, Chan L, Tan KC. e impact of skin
banking and the use of its cadaveric skin allogras for severe burn
victims in Singapore. Burns. 2004;30(7):696-700.
12. Germain N, Hatzfeld AS, Pasquesoone L, Danze PM, Guerreschi
P, Sendid B, Gaillot O, Marchetti P. How to improve donor skin
availability: Pragmatic procedures to minimize the discard rate
of cryopreserved allogras in skin banking. Burns. 2020:S0305-
4179(20)30463-0.
13. Woll JE, Kasprisin D, editors. Standards for Tissue Banking.
McLean, VA: American Association of Tissue Banks; 2001. p. 46–52.
14. Saegeman VS, Ectors NL, Lismont D, Verduyckt B, Verhaegen
J. Short- and long-term bacterial inhibiting eect of high
concentrations of glycerol used in the preservation of skin allogras.
Burns. 2008;34(2):205-211.
15. Cleland H, Wasiak J, Dobson H, Paul M, Pratt G, Paul E, Herson
M, Akbarzadeh S. Clinical application and viability of cr yopreserved
cadaveric skin allogras in severe burn: a retrospective analysis.
Burns. 2014;40(1):61-66.
16. Kua EHJ, Goh CQ, Ting Y, Chua A, Song C. Comparing the
use of glycerol preserved and cryopreserved allogenic skin for the
treatment of severe burns: dierences in clinical outcomes and in
vitro tissue viability. Cell Tissue Bank. 2011;13:269-279.

Popa L.G. et al.
44
17. Blome-Eberwein S, Jester A, Kuentscher M, Ra T, Germann
G, Pelzer M. Clinical practice of glycerol preserved allogra skin
coverage. Burns. 2002;28:10-12.
18. Huang Q, Pegg DE, Kearney JN. Banking of non-viable skin
allogras using high concentrations of glycerol or propylene glycol.
Cell Tissue Bank. 2004;5:3-21.
19. Lomas RJ, Cruse-Sawyer JE, Simpson C, Ingham E, Bojar R,
Kearney JN. Assessment of the biological properties of human split
skin allogras disinfected with peracetic acid and preserved in
glycerol. Burns. 2003;29(6):515-525.
20. Gore MA, De AS. Deceased donor skin allogra banking: Response
and utilization. Indian J Plast Surg. 2010;43(Suppl):S114-120.
21. Mosti G, Mattaliano V, Magliaro A, Picerni P, Bastiani L. Cad averic
Skin Gras May Greatly Increase the Healing Rate of Recalcitrant
Ulcers When Used Both Alone and in Combination With Split-
ickness Skin Gras. Dermatol Surg. 2020;46(2):169-179.
22. Choi YH, Cho YS, Lee JH, Choi Y, Noh SY, Park S, Sung C, Lim
JK, Kim J, Shin JJ, Yang B, Jeong J, Chun H, Kim KJ. Cadaver skin
allogra may improve mortality rate for burns involving over 30%
of total body surface area: a propensity score analysis of data from
four burn centers. Cell Tissue Bank. 2018;19(4):645-651.
23. Robb EC, Bechmann N, Plessinger RT, Boyce ST, Warden GD,
Kagan RJ. Storage media and temperature maintain normal anatomy
of cadaveric human skin for transplantation to full-thickness skin
wounds. J Burn Care Rehabil. 2001;22(6):393-396.
24. Miron A, Giulea C, Tudose I, Petrache D, Giurcaneanu C.
Pyoderma gangrenosum, rare parietal complication aer colorectal
surgery. Chirurgia. 2014;109(2):248-253.
25. Lowery K, Shirley R, Shelley OP, Kaniorou-Larai M, Philp B,
Dziewulski P. Purpura fulminans skin loss: surgical management
protocols at a regional burns centre. J Plast Reconstr Aesthet Surg.
2008;61(12):1520-1523.
26. Miron A, Giulea C, Nadragea M, Enciu O. e Laparoscopic
Approach of Small Bowel Obstruction-e Experience of a Primary
Center. Chirurgia. 2016;111(2):126-130.
27. Calu V, Dumitrescu I, Miron A. e role of laparoscopy in
the surgical treatment of scleroatrophic cholecystitis. Chirurgia.
2010;105(5):653-656.
28. Zhou H, You C, Wang X, Jin R, Wu P, Li Q, Han C. e progress
and challenges for dermal regeneration in tissue engineering. J
Biomed Mater Res A. 2017;105(4):1208-1218.
29. Wong AK, Schonmeyer BH, Singh P, Carlson DL, Li S, Mehrara
BJ. Histologic analysis of angiogenesis and lymphangiogenesis in
acellular human dermis. Plast Reconstr Surg. 2008;121(4):1144-1152.
30. Chauviere MV, Schutter RJ, Steigelman MB, Clark BZ, Grayson
JK, Sahar DE. Comparison of AlloDerm and AlloMax tissue
incorporation in rats. Ann Plast Surg. 2014;73(3):282-285.
31. Reiel AJ, Henderson PW, Krijgh DD, Belkin DA, Zheng Y,
Bonassar LJ, Stroock AD, Spector JA. Mathematical modeling and
frequency gradient analysis of cellular and vascular invasion into
integra and strattice: toward optimal design of tissue regeneration
scaolds. Plast Reconstr Surg. 2012;129(1):89-99.
32. Naoum JJ, Roehl KR, Wolf SE, Herndon DN. e use of
homogra compared to topical antimicrobial therapy in the
treatment of second-degree burns of more than 40% total body
surface area. Burns. 2004 Sep;30(6):548-551.
33. Spies M, Sanford AP, Aili Low JF, Wolf SE, Herndon DN.
Treatment of extensive toxic epidermal necrolysis in children.
Pediatrics. 2001;108(5):1162-1168.
34. Pianigiani E, Ierardi F, Taddeucci P, Perotti R, Biagioli M,
Di Simplicio FC, Andreassi A, Fimiani M. Skin allogra in the
treatment of toxic epidermal necrolysis (TEN). Dermatol Surg.
2002;28(12):1173-1176.
35. Burd A, Lam PK, Lau H. Allogenic skin: transplant or dressing?
Burns. 2002;28(4):358-366.
36. Tenenhaus M, Rennekamp HO. Burn surgery. Clin Plast Surg.
2007;34(4):697-715.
37. Zhang ML, Chang ZD, Wang CY, Fang CH. Microskin graing
in the treatment of extensive burns: a preliminary report. J Trauma.
1988;28(6):804-807.
38. Reverdin H. Jaques-Louis Reverdin (1842-1929). Un chirurgien
á l’aube d’une ere nouvelle. Verlag Sauerlander, Aarau, Switzerland,
1971.
39. Reverdin J L. Gree epidermique-Experience faite dans le
service de M. le docteur Guyon, á l’hópital Necker. Bull Soc Imp de
Chir de Paris 1869;10:511-515. Reimpreso en: Plast Reconstr Surg
1968; 41:79-82.
40. Maqsood SE, Cascone N, Grixti A, Kannan R, Nduka C, Malhotra
R. Functional and aesthetic outcomes of eyelid skin graing in facial
nerve palsy.British Journal of Ophthalmology. 2019;103: 686-691.
41. Klasen H.J. (1981) Skin Graing in Eyelid Surgery. In: History
of Free Skin Graing. Springer, Berlin, Heidelberg. https://doi.
org/10.1007/978-3-642-81653-6_3, ISBN 978-3-642-81655-0, 978-
3-642-81653-6.
42. Catherine J. Choi, Alain Bauza, Michael K. Yoon, Rachel
K. Sobel,Suzanne K. Freitag. Full-ickness Skin Gra as an
Independent or Adjunctive Technique for Repair of Cicatricial
Lower Eyelid Ectropion Secondary to Actinic Skin Changes.
Ophthalmic Plast Reconstr Surg. 2015;31(6):474-477.
43. van Diest PJ, Lopes Cardoso NWJ, Niesing J. Cadaveric tissue
donation: a pathologist’s perspective. Journal of Medical Ethics
2003;29:135-113.
44. Hornicek. AATB standards for tissue banks. 10th edition.
McLean, VA: AATB; 2002. p. 112.
45. European Commitee (partial agreement) on organ
transplantation (CD-P-TO). 4th edition of the guide to the quality
and safety of tissues and cells for human application. 2019. https://
www. edqm.eu/en/organs-tissues-and-cells-technical-guides.
Accessed 2021 Jan 20
46. Wei LG, Chen CF, Wang CH, Cheng YC, Li CC, Chiu WK,
Wang HJ. 500-Gray γ-Irradiation May Increase Adhesion Strength
of Lyophilized Cadaveric Split-ickness Skin Gra to Wound Bed.
Ann Plast Surg. 2017;78(3 Suppl 2):S135-S138.
47. Barry Lillie, Silvia Donati. Italy’s Ancient Medical Schools:
Anatomical eatres. Wed, 10/29/2014. Accesat in 8.05.2019
[https://www.italymagazine.com/featured-story/italys-ancient-
medical-schools-anatomical-theatres].
48. Ethics of Organ Transplantation, Center for Bioethics February
2004, University of Minnesota, accessed February 20t h 2021 [https://
www.ahc.umn.edu/img/assets/26104/Organ_Transplantation.pdf].
49. Childress JF. e Failure to Give: Reducing Barriers to Organ
Donation. Kennedy Institute of Ethics Journal. 2001; 11(1):1-16.
47. United Network for Organ Sharing website. www.unos.org.
50. Kluge EH. Drawing the Ethical Line Between Organ
Transplantation and Lifestyle Abuse. Canadian Medical Association
Journal. 1994; 150(5):745-746.
51. Williams A. e rationing debate: Rationing health care by age:
e case for. British Medical Journal. 1997; 314:820.
52. Ubel PA, Arnold RM, Caplan AL. Rationing failure:
Retransplantation of scarce, vital organs in the US. Journal of the
American Medical Association. 1993; 270:2469- 2474.
53. van Diest PJ, Lopes Cardoso NWJ, Niesing J. Cadaveric tissue
donation: a pathologist’s perspective. Journal of Medical Ethics.
2003;29:135-113.
54. Nunnink L, Stobbs N, Wallace-Dixon C, Carpenter B. Does
organ donation impact on forensic outcomes? A review of coronial
outcomes and criminal trial proceedings. Journal of forensic and
legal medicine. 2019;68:101860.
55. Grigoraş I, Blaj M, Florin G, Chelarescu O, Craus C, Neagu R.
e rate of organ and tissue donation aer brain death: causes of
donation failure in a Romanian university city. InTransplantation
proceedings 2010; 42(1): 141-143.
56. Bratton, Charles; Chavin, Kenneth; Baliga, Prabhakar Racial
disparities in organ donation and why, Current Opinion in Organ
Transplantation. 2011;16(2):243-249.