Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / @xirurgi_2025 / @xirurgi_2025 - 380 - файл
.pdf
248
https://t.me/medicina_free
V. Cazzato et al.
substitutes. It is made of three polypeptide woven
bers with a length of about 1000 AA each [9].
Different types of collagen can supply different
properties, depending on their animal origin: most
common sources of collagen are bovine tendons,
swine skin, intestines, bladder mucosa, and mouse
tail [20, 21]. Due to the risk of disease transmission, the trend is to produce synthetic collagen
[22]. Collagen makes up for about 70% of the raw
weight of the dermal matrix and is mainly represented by type I collagen; [23] other types of collagen include type III and V.Despite its important
properties (high level of biocompatibility, biodegradability, adhesion, proliferation, and migration-enhancing abilities), its mechanical resistance
is lower than that of the normal skin [24].
To solve this issue, collagen bers are woven
with other biomaterials such as chitosan, GAG,
HA, brin, gelatin, elastic. Pullulan, alginate,
laminin, polylactic acid (PLLA) polyglycolideco- L -lactide (PLGA), polietilenglycole (PEG) e
poli-ε-caprolactone (PCL).
Hyaluronic acid. This is a linear polymer
formed by glucuronic acid and N-acetyl glucosamine. Peculiar characteristics make it an appropriate biomaterial for cutaneous tissue
engineering, and these include easy production
process, biodegradability, scavenger action of
free radicals, null immunogenicity, and nonadhesiveness. Hyaluronic acid induces early
inammation which is necessary to start the healing process and for this reason represents one of
the most used biomaterials [25]. When compared
to pure collagen scaffolds, the combination of
HA and collagen has demonstrated a greater
migration and cellular division.
Gelatin: it is made of a specic triplet-ArgGly-Asp (RDG), which improves its interaction
with cells through integral receptors found in cell
membranes. Lysin and arginine residues add to
gelatin the ability to adhere to the cell membrane
[26]. When compared to collagen, it could be
used as dressing in wounds at high risk of infection, due to minor antigenicity [9, 27]. Gelatin’s
conformational structures depend on temperature, solvents or pH, so it could be useful for the
continuous release of growth factors [28]. Despite
being able to absorb large quantities of water,
which provides a suitable micro-environment for
cell migration, adherence, proliferation, and
angiogenesis, it can also reduce broblasts’
migration, except when combined with other
polymers [6, 7, 29].
Fibronectin and brin act as structural elements
to promote migration of keratinocytes, neutrophils, macrophages, and broblasts, crucial to
begin the wound’s healing process [30]. Fibrin has
high afnity for proteins, so it can bind various
growth factors to improve angiogenesis and cell
adhesion to the scaffolds [31] Fibrin also has the
ability to induce the production of cells. It has also
been considered an important source of crucial
growth factors involved in the processes of wound
repair [32]. Fibronectin is another important glycoprotein of the cutaneous extracellular matrix,
derived from the human or bovine plasma in its
soluble form. With its high molecular weight, it is
able to bind collagen, brin, and heparin. Like
brin, bronectin exerts a positive action on adhesion, proliferation, and contraction of cells
involved in wound healing. Moreover, it not only
increases the availability of growth factors; it also
raises their levels of expression and can create specic gems for neural regeneration [33].
Elastin is one of the fundamental proteins of
the connective tissue, responsible for the skin’s
elasticity. Since collagen-based scaffolds suffer the lack of adequate elasticity, when elastin
is combined with collagen, it could reduce the
wound’s contraction and make the dermal substitute more elastic and similar to normal skin
[10]. Elastin-based scaffolds have shown to
reduce scar formation and support skin
regeneration.
24.3 Classications
Nowadays, the European market gives access to a
wide range of cutaneous substitutes with various
characteristics and multiple possible classications, based on the impact that these substitutes
exercise on tissue regeneration.
As previously stated, composition and breakdown time are fundamental characteristics for the
description of the products, and these characteris-
24 Skin Substitutes
https://t.me/medicina_free
249
tics are also necessary to differentiate them,
according to their diverse inuence on tissue
regeneration, into permanent dermal substitutes
and granulation tissue bio-inductors. This partitioning better allows clinicians to have a guide on
the clinical application of these products; however, it is worth mentioning the other existing relevant classications widely in use as well.
Starting from 2001 Balasubramani etal. [34]
have suggested a classication system including
3 categories or classes based on the skin layers.
Class I equaled an epidermal substitute in coculture. Class II included dermal components from
treated skin or made of collagen and other ECM
proteins. Class III contained products with distinct epidermal and cutaneous components.
This system, however, does not differentiate
between cellularized and non-cellularized products, nor the source (human, animal, or synthetic
origin). In 2008, Kumar introduced a 3-category
system based on whether the substitute was permanent or temporary. Class I included material
for impermeable and temporary material. Class II
included single-layer permanent skin substitutes
and Class III included double-layer permanent
skin substitutes. Ferreria etal. in 2011 [35] proposed a more complete classication system
based on three criteria: which skin layer was to
be replaced, the duration in the wound bed, and
the origin of the scaffold material. 21 Three categories were identied for the “skin layer” criterion of product: epidermal (E), dermal (D), and
dermal/epidermal compound (C). Two categories
have been identied for the “duration” criterion:
temporary (T) and permanent (P).
As for the criterion of origin material, three
categories have been identied: biological (b),
which includes human and animal, biosynthetic
(bs), and synthetic (s). In 2016, the American
Society for Testing and Materials International
(ASTM) [36] published standardization guidelines for the classication of cellular and/or
tissue- based (CTP) products used in skin wounds.
In this work, it was stated that CTPs are mainly
dened by their composition and include cells
and/or extracellular components of the
ECM. CTPs may contain cells (viable or nonviable), tissues, proteins, and other materials for
which there is evidence of benet compared to
that obtainable with conventional dressings.
CTPs may also include synthetic components.
The guide also has a classication system for
CTPs based on four composition categories: biosynthetic, biosynthetic and animal, nonliving
based on biological living tissue and cells. The
category based on nonliving tissues is further
divided by source (human or animal) and the biological category of living cells is subdivided by
processing (minimal, cultured, cultured, and animal). In 2018, Davison-Kotler etal. [37] proposed
a new classication system for skin substitutes
based on the older systems and corrected their
deciencies, in particular some confusing and
non-intuitive categories (in some systems, acellular and cellular products could be placed in the
same category). This new system organized skin
substitutes based on cellularity, stratication, and
skin components to be replaced, materials used,
and permanence. The authors considered cellularity to be the most important discriminant among
skin substitutes, considering that the presence of
cells increases the risk of rejection and increases
manufacturing complexity. The layering comes in
one or two layers, with the double layer generally
replacing both the dermis and the epidermis. The
replaced region indicates whether the product is
intended to replace the dermis, the epidermis, or
both. The composition of the product determines
which layers it is intended to replace. The materials used to produce the leather substitute can be:
natural (of human or animal origin), synthetic, or
both. Permanence is described as biodegradable
(temporary) and non-biodegradable (permanent).
These parameters are used in a factorial design to
produce a grading system that can be used for any
new or old skin substitute.
24.4 Main Skin Substitutes
ontheMarket
In this section, we will analyze the main skin substitutes available on the market and their characteristics. For simple understanding, the products
can been divided into permanent and granulation
tissue bio-inductors/temporary skin substitutes.
250
https://t.me/medicina_free
V. Cazzato et al.
Taking into account that this subdivision reects
specic invitro characteristics (already described
above), and in vivo where the “permanence”
characteristic is related to the ability that the dermal substitute has to take root.
Dermal
matrix In vitro In vivo
Permanent Bioconduction Engraftment Neodermis
Bioinduction Granulation
Temporary Bioinduction Enzymatic
breakdown
Mechanical
removal
Type of
healing
tissue
Granulation
tissue
Integra® was developed in the early 1980s and
was the rst dermal substitute to be developed.
Its goal was to minimize uid loss and bacterial
contamination and promote cell migration into
the wound bed [38].
It comes with a two-layer composition. The
deepest layer of Integra® is made up of a combination of bovine collagen and glycosaminoglycan chondroitin-6-sulfate, while the supercial
layer is composed of a 0.2mm thick polysiloxane
polymer membrane with vapor transmission
characteristics. This membrane can be placed
over the full thickness of the wound and the silicone outer membrane will act as a temporary epidermal substitute. This feature requires
replacement of the outermost membrane with a
split-thickness skin graft (STSG) after about
2–3weeks. By combining it with a silicone layer
as a temporary epidermal cover, Integra® can
immediately act as a barrier while providing the
extracellular scaffolding necessary for internal
cell growth and proliferation of broblasts and
endothelial cells. After 2–3weeks, when internal,
cellular, and vascular growth is complete, the silicone layer is replaced by a partial-thickness skin
graft. In recent years, many studies have proven
its different indications (skin ulcers, burns, necessity to ll in spaces or improve scar quality). The
use of negative pressure therapy (TPN) on the
silicone layer has been described and it has been
shown that in some cases it can reduce the time it
takes for the replacement to revascularize by up
to 10days. The benets of using Integra include
adequate long-term wound coverage as well as a
reduction in hypertrophic scar formation and
itching. Disadvantages include high costs and
some reported infectious complications.
Matriderm®: is an extracellular matrix scaffold based on a puried and lyophilized bovine
collagen mix (type I, III, IV) with 3% elastin
hydrolyzate and has an integration/degradation
time of 6weeks. It is usually applied in one-time
procedures as this dermal scaffold allows for
immediate coverage with (STSG). However, this
one-step procedure showed slower graft take due
to the interposition of the non-vascularized scaffold between the wound bed and the graft itself.
However, the results in terms of scar quality were
superior to the exclusive treatment with STSG
even after a 12-year follow-up [126]. Matriderm®
promotes neoangiogenesis and the construction
of a new stable and highly elastic tissue.
Pelnac® is a matrix of porcine origin. This dermal substitute is available both with and without a
silicone layer and also in the fenestrated type. These
features make it suitable for both single- stage and
two-stage procedures. It is mainly used in Asia, but
has recently become available in Europe as well. It
promotes the inltration of broblasts and neoangiogenesis and can be used above all for very thick
defects, wounds with a high risk of infection and
wounds that should rise from the bottom.
Cultured epidermal autografts (CEAs): represent an additional available approach for wound
coverage. These skin grafts are grown in the laboratory for several weeks after obtaining a biopsy from
the patient’s skin, after which the grafts are applied
to the wound bed. Most surgeons limit the use of
CEA to extensive burns when there is little or no
donor site. This approach is extremely expensive
and CEAs present with advantages and disadvantages, mainly related to the thin and brittle nature of
these grafts. Once attached, the graft is highly susceptible to shear forces and, once healed, the grafts
remain fragile and prone to injury for an extended
period of time compared to standard STSGs. Epicel
(Genzyme Biosurgery, Cambridge, MA) is the bestknown CEA system available on the market.
Integra (single layer): Integra Life Science has
also developed a single-layer version of their traditional Integra double layer. Integra single layer is an
acellular matrix based on permanently cross-linked
24 Skin Substitutes
https://t.me/medicina_free
251
collagen and glycosaminoglycans. It is 1.3 mm
thick and consists of only a dermal replacement
component. The main objective of the product is to
be able to perform a surgical procedure in one stage,
with the simultaneous application of an STSG.
Alloderm® is based on “traditional cadaver
skin”; it is one of the rst acellular allogeneic skin
substitutes developed and represents real human
tissue taken as a skin graft from a cadaver donor.
Alloderm® is washed with hypertonic saline to
remove cellular remains. The remaining dermal
layer is treated with inactivating viruses and then
lyophilized for use. This provides a non- antigenic
dermal scaffold with basal membrane proteins.
After rehydration of Alloderm®, coverage with
STSG is sufcient as a denitive treatment option.
Renoskin Renoskin (Symatese, Ivry-leTemple, France): is a 2-mm-thick bilaminar skin
substitute available in Europe until a few years
ago. It consists of type 1 bovine collagen and a
silicone lm. It was used in acute burns. The
same manufacturer now produces NEVELIA, a
double-layered matrix consisting of a layer of
collagen to promote dermal regeneration and a
reinforced silicone layer that acts as a pseudoepidermis. This product, as emerges from a 2020
study by Montanaro M etal., appears to have the
ability to activate macrophages and M2 cells during the tissue repair process [39].
Myriad: Myriad Matrix™ is an engineered
extracellular matrix (ECM) for soft tissue repair,
reinforcement, and complex wounds. Myriad
Matrix™ devices contain the natural porous
structure of AROA ECM™, engineered with
interstitial perforations to enable cell inltration
to facilitate rapid healing. The matrix rapidly
absorbs blood and its components to form a reservoir of biologically important cells and cell
components to aid tissue repair process.
Fibroblast, endothelial, and immune cells inltrate the entire matrix and build new tissue and
over time Myriad Matrix™ is completely remodeled by the patient’s own tissue [40].
Kerecis: This substitute is composed by an
acellular sh skin, which is very rich in polyunsaturated fatty acids omega 3, with a microstructural composition extremely like the human
dermis. Kerecis seems to be suitable in order to
obtain a very “natural” skin and to reduce pain.
The analgesic effect plus a 100% reepithelization
was reported in 2019 by Alam K etal. [41] on 10
donor split-thickness sites on burned patients. In
the same year, Michael S etal. [42] described a
retrospective case series of 58 diabetic ulcers in
which they obtained both 54 surface reduction in
87.57% and complete healing in 60.34%.
Allografts: cadaver skin has always been the
rst choice for temporary cover. Despite the
potential risks of infection from its use and its
high cost, it has gained popularity due to its ability to be used as an allograft and of providing
lasting coverage over a long period of time (compared to other temporary dressings), providing
coverage of the wound for 3–4 weeks. Fresh
allograft remains viable for up to 14days when
stored in a suitable nutrient medium. The cryopreserved allograft can be stored for a longer
period of time and maintains good viability. Used
as a biological dressing, this grafted homologous
tissue is characterized by an early pseudoengraftment phase and an immunological rejection phase after 2–3weeks. During the rejection
phase, it stimulates a physiological debridement
through the macrophages with consequent physiological preparation of the wound bed.
Xenografts: Over the years, the skin of multi-
ple animal species has been used as a temporary
skin cover. Xenografts can provide temporary
coverage when allografts are not available or are
prohibitively expensive. Due to their inability to
fully re-vascularize, they should be viewed more
as a dressing rather than as a true skin substitute.
Xenografts have been shown to slow evaporative
uid loss, reduce infections, and increase autologous epidermal growth. Most surgeons use xenografts as dressings to cover partial-thickness
burns, donor sites, and wounds in the context of
toxic epidermal necrolysis. The benets of xenografts include low cost, extended shelf life, and
wide availability. The disadvantages include possibility of transmission of infectious agents as
well as some cultural and religious issues.
Dermagraft® is a very interesting and successful
product, especially for the diabetic foot. It can be
described as an allogeneic cell culture that uses neonatal skin broblasts grown on a biodegradable
252
https://t.me/medicina_free
V. Cazzato et al.
scaffold and has the ability to secrete various growth
factors to stimulate neoangiogenesis and re-epithelialization. Finally, its effectiveness is maintained
even after cryopreservation and thawing.
Apligraf® consists of a type I bovine collagen
matrix on which human allogeneic neonatal epidermal keratinocytes derived from the foreskin
are then cultured and stratied. These characteristics make it subject to rejection and therefore
requires an autologous skin cover with graft, to
obtain a denitive closure. An acute inammatory
response occurs in patients treated with Apligraf®,
with an acceleration in the formation of granulation tissue. Apligraf is currently approved by the
FDA for use in the treatment of diabetic foot and
venous ulcers, although it is also used in the treatment of burns. The cost, however, is very high.
Novosorb (Polynovo, Melbourne, Australia):
it is a biodegradable temporary matrix that represents a completely synthetic dermal regeneration
model currently still under study. Preliminary
data compared with Integra show a more extensive vascular network in favor of Novosorb but
also a greater inammatory response.
Hyalomatrix (Anika, Boston, MA) is a dermal
substitute based on HYAFF, an extended derivative of hyaluronic acid. It is a bioabsorbable dermal substitute that has been described to be used
for coverage of acute burns. The product allows
rapid formation of granulation tissue and requires
a secondary skin graft.
Endoform unique extracellular matrix (ECM)
products for the management of acute and chronic
wounds. Endoform™ products support all phases
of wound healing and are appropriate for use early
in wound management to restore protease balance
and advance healing to the proliferative phase [43].
24.5 Clinical Overview
Dermal substitutes should be applied onto an optimal
wound bed: this journey can be long and divided into
different stages. During this process, the surgeon is
able to evaluate the real healing potential of the individual patient and is therefore able to calibrate the
reconstructive objectives and end points specically
for each patient. In this way, the best possible treat-
ment is guaranteed to achieve an outcome that is realistic for the patient’s condition and functionality.
Wound bed preparation begins with the DiagnosticInstrumental framework of the patient and the wound.
It starts with a general patient’s clinical status assessment based on comorbidity, nutritional structure, glycemic control; these factors must always be kept
under control during the treatment of the lesions, also
to avoid relapses or new onset lesions. Control of the
underlying pathology of chronic wounds is important
at a loco-regional level, for example with surgery in
supercial IVC or with bandaging in deep IVC, as
well as with decubitus correction in neuropathic diabetic foot. In acute wounds, such as burns and trauma,
if no other comorbidities coexist, the local aspect of
the wound (etiology, localization, exposure of noble
structures) and the assessment of the anatomical context in which it arises are more important.
To allow optimal performance of the dermal
template, the most important aspect is certainly
the vascularization which must be evaluated with
instrumental tests such as:
• Eco-color doppler, with optimal values being:
• Peak speed in receiving artery >40cm/s.
• ABI>= 0.7+biphasic ow
• CT Angiography with optimal values being:
• At least 1 accessible leg artery
• CTPO2<30mmHg which indicates need for
revascularization.
In fact, most of the wound’s healing potential
will depend on the local vascular situation. In this
regard, if the instrumental tests show a signicant
reduction in blood ow, an attempt to revascularize will be necessary.
Following revascularization, the real success
of the procedure will be assessed through TcPO2
test that can prove whether the healing power has
increased or not. In the rst case, it will be possible to proceed with wound bed preparation
through debridement, with or without stimulation
(also through bio–inductors) to ultimately obtain
a surface that allows reconstruction for example
through positioning of a bio-conductor. In this
case, it is clear that the aim is to achieve the maximum functional result. However, a different consideration must be made when, despite an
24 Skin Substitutes
https://t.me/medicina_free
253
adequate diagnostic-therapeutic approach, the
patient keeps showing poor healing potential (it
is the case of diabetic foot with non-eradicated
infection, failed revascularization attempts, inadequate nutritional values). In this case, it is necessary to commensurate goal expectations to the
real patient’s healing potential and to the possible
economic investment: an attempt can be made to
stimulate granulation tissue from the bottom with
NPT, enzymatic debridement, and bio-inducers
rather than bio-conductors whose properties
wouldn’t be optimally exploited. All this to say
that the choice of a biomaterial must always be
related to the type of wound and the type of
patient, in a way to make the most out of all of the
dermal substitutes’ properties, without leading to
over-treatment or inappropriate treatments.
A concrete example of what has been said is the
treatment of chronic wounds in which there is no
possibility of eradicating or resolving the triggering cause, and for this reason, it is necessary to
adapt the healing goals to reality by favoring treatments aimed at stimulating and cleaning the
wound. On the other hand, in the case of wounds
originating from acute events (e.g., road trauma in
healthy subjects), once the reasons for non- healing
have been identied and treated (infection, tissue
sequestration, means of synthesis, reduced vascularization), it is necessary to focus on obtaining the
restitutio adintegrum using bio- conductive dermal
substitutes associated or not with a skin graft. The
two examples mentioned above prove that tissue
losses in need of coverage can be very different
from each other with different obtainable nal
results. Wounds that may require the use of a skin
substitute to heal include: pathological scars, postoncological tissue loss, wounds in pressure areas
and/or particular anatomical areas, wounds with
exposure of noble tissues, diabetic foot, posttrauma wounds and contaminated wounds, chronic
ulcers. All these wounds have in common healing
difculty with different healing potentials or reconstructive challenges, despite having completely different causes and factors. For this reason, for each
of these situations it is necessary to understand the
problem and the realistic obtainable result in order
to be able to use the most suitable biomaterial for
the type of wound and its phase.
To this date, however, there is little evidence
in the literature regarding which dermal substitute is best according to the type of wound we are
facing. For this purpose, it is essential to use
one’s own clinical experience. In particular, our
unit mainly uses substitutes that have been on the
market for the longest time, and with which we
have gained clinical experience that allows us to
understand when and where to use them, with the
aim of obtaining the best texture and fewer local
recurrences. In our clinical experience, to date,
the permanent bio-conductive dermal substitute
whose efcacy and neodermis formation has
been demonstrated with numerous clinical studies, with several years of follow-up, on the market for a longer time, is the Integra: with this
dermal substitute we obtain the best and safest
results with a high percentage of engraftment
(close to 100%) and good skin texture, better than
the one obtainable with skin graft alone.
The slow engraftment of Integra (in addition
to the indications mentioned before) allows us to
use it also in post-oncological excisions performed in two surgical steps, with sample being
sent for histological examination (slow Mhos
type) within 3–4days and subsequent reconstruction only if conrmed radicality, as we can
remove it before reconstructing if the histological
examination still reports presence of disease [44].
Scalp reconstruction is a perfect example, given
that integra is also effective for large and deep
lesions that include bone exposure: this means that
deeper, more radical resection can be performed
and covered with the dermal substitute [45].
Moreover, its easy access to tumor site allows
for easier follow-up and consequently detection
of recurrence, whereas free ap coverage or other
traditional reconstructive options can cover up
any of these signs and also help spread residual
disease. Dermal substitutes are the only coverage
solutions when waiting for histopathological
results in two-step reconstructive strategies.
As widely proven in current literature, Integra
stimulates vascularization of the wound bed and,
likely, of the surrounding tissues so it is an ideal
solution for irradiated tissues in which healing
potential is limited by destruction of local broblasts and reduced blood ow. Even when subse-
254
https://t.me/medicina_free
V. Cazzato et al.
quently irradiated, Integra-covered tissue displays
overall good outcome with mean graft take of 95%.
Finally, Integra is the optimal solution for tissues who have already undergone surgical procedures and have developed scarring tissue, since
the latter makes further traditional approaches
unpredictable.
When a large gap is present between the bottom of a wound and the surrounding healthy tissue, in some selected cases, our experience (also
supported by literature) suggests to serially apply
several layers of the same SD, with a 3-week wait
between applications, until the bottom of the
wound is raised to a correct level; it is then possible to opt for a skin graft or an epidermal substitute to heal the surface. Therefore, future
challenges will concern deep wounds, perhaps
with exposure of noble tissues or in loading areas
where the reconstructive surgical indication so
far has been a free ap and not a skin graft: to this
day, there is indication for skin grafts on boney
structures, as long as these are highly vascularized and do not support physical load [46]. In
areas where vascularization is not adequate,
“bridging” phenomenon can take place: this is
the ability of a skin graft to survive across a limited avascular bed [47]. Findings suggest that a
skin graft may bridge a larger avascular defect if
the surrounding bed is adequately prepared [48]
that a temporary angiogenic response also starts
within local capillaries in the center of fullthickness skin grafts which implies that bridging
of the vasculature takes place from the edge as
well as from the center of a graft [49]. Future
investigations may try to combine DS with autologous cells or heterologous cells to avoid donor
site morbidity to increase its thickness or even
allow it to take in poorly vascularized areas,
therefore increasing its indications.
On wounds where there is no certainty of their
high healing potential, one may also use bioinductors to stimulate the formation of granulation tissue and a secondary healing. Where one is
more sure (based on the patient’s comorbidities
and the local wound situation) about the healing
potential, after adequate debridement, we may
place bio-conducting materials with the aim of
obtaining the best and permanent result. This is
guaranteed by the complete engraftment of the
substitute and the formation of a compact and
stable neodermis over time that can also stimulate
the epidermis of the subsequent graft to integrate
perfectly, as can be demonstrated histologically
with the presence of the dermal papillae [50].
Temporary DSs do not have time to bio- conduct
and are instead bio-inductors that induce formation of granulation tissue, whereas permanent dermal substitutes can instead act as bio- conductors
in vitro, [51] allowing cellular growth: clinically
speaking, whether this transforms into neodermis
or granulation tissue depends on the modality and
rapidity of cellular proliferation (Fig.24.1).
To prove the presence of an effective neodermis, histological samples should be retrieved
even a long time after the graft has healed [13]
(Figs.24.2 and 24.3).
Nowadays, other products that have also been
present for some time in Europe, such as Matriderm,
Pelnac, Nevelia, Myriad, Novosorb, and others
mentioned previously, are making their way in the
Italian market as well and will have to show the
same performances as Integra. Ideally, these results
should be histologically evaluated through biopsies
of the newly formed tissue after years, and these
samples should show whether a neodermis similar
to the autologous dermis is formed, if the substitute
is still present, or if there is no dermal organization
but rather a scar-like one.
Until histological evidence of neodermis
reconstitution will not be obtained in authorized
large studies (examples in Figs.24.2 and 24.3), to
be able to differentiate the performance of each
material we can clinically rate elasticity/texture
of the skin in the long term, since the take of the
graft can be faster even on thinner substitutes
with high cellularization that do not form a real
neodermis but rather granulation tissue.
In particular, we will be satised with assessing
certain clinical factors that are evaluators of tissue
quality. In the clinical setting, several methods are
available for the holistic assessment of dermal
substitutes: clinical outcomes were determined
through subjective assessment of healing time
using Manchester Scar Scale (MSS) and Visual
Analog Scale (VAS), Multi Probe Adapter System
MPA [52] Observer Scar Assessment Scale
ab
e
between the fluorescence of the cells seeded in the scaffold and the fluorescence of the total
24 Skin Substitutes
https://t.me/medicina_free
255
1.0
0.8
0.6
0.4
total seded cells
0.2
colonizating cells/
0.0
cd
120
100
80
60
40
20
% of proliferating cells
0
*
**
Integra
Integra
PriMatrix
PELNAC
PELNAC
Endoform
Hypoxic Conditions Diabetogenic Conditions
PriMatrix
Endoform
n.s.
**
Myriad
*
Myriad
70
60
50
40
30
20
20
% of proliferating cells
0
120
100
80
60
40
20
% of proliferating cells
0
Integra
Integra
n.s.
PELNAC
PELNAC
*
PriMatrix
PriMatrix
Endoform
Endoform
e
Integra
Hypoxic
Condition
Diabetogenic
Condition
PELANC Primatrix
Endoform Myriad
**
**
Myriad
*
Myriad
Untreated
cells
No cells
Ki-67 Vimentin
See this image and copyright information in PMC
Figure 3 (A) After 36 h of culture onto the different dermal substitutes, ADMECs were stained
with the fluorescent dye FAST Dil; labelled cells were lysed to releasee the dye in solution, and th
fluorescence was read at 353 nm with Infinite200 TECAN reader. Results are expressed as a ratio
Fig. 24.1 (a) After 36 h of culture onto the different der-
mal substitutes, ADMECs were stained with the uorescent dye FAST Dil; labelled cells were lysed to release the
dye in solution, and the uorescence was read at 353 nm
with Innite200 TECAN reader. Results are expressed as
a ratio between the uorescence of the cells seeded in the
scaffold and the uorescence of the total number of cells.
Data from ve independent experiments are presented as
mean ± SE. * p < 0.05; ** p < 0.01 vs. Integra®. (b–e)
The cell-colonized scaffolds under resting conditions (b),
(d) were xed and stained with mouse antihuman vimentin and rabbit antihuman Ki67 antibodies and analyzed by
the uorescent scanner Odyssey CL-x (LI-COR
Biosciences, Lincoln, NE, USA). (e) A representative
image of labelled scaffolds was acquired by using LI-COR
Odyssey imaging system, and data were processed using
Image Studio system 5.0 software (LI-COR Biosciences,
Lincoln, NE, USA). Data from four independent experiments conducted in triplicate are presented as mean ± SE.
* p < 0.01 vs. Integra; n.s. = not signicant
under hypoxic conditions (c) or diabetogenic conditions
256
https://t.me/medicina_free
Fig. 24.2 Reconstruction using double-layer skin substitute, biopsy 5 years after surgery, neodermis (original
magnication x20) [13].
Fig. 24.3 Single-layer substitute and normal skin, biopsy
6months after surgery (original magnication x5) [13].
(POSAS) [53]. Other functional anatomical
parameters taken into account include: corneometry; transepidermal water loss; elastometry; colorimetry; ultrasound skin scan model; and 3D skin
surface model [54]. Once the dermal substitute is
positioned at the defect level, there are several outcome parameters for its evaluation. Outcome is
certainly one of the most important short- and
long-term parameters for evaluating the nal success of surgical reconstruction using a skin substitute. Various factors are taken into account, such as
engraftment success, texture or consistency of the
neo-skin, color, resistance, perspiration capacity,
and prole. The closer these qualities are to normal skin, the more the substitute will obtain a good
result and therefore a good outcome. The single
V. Cazzato et al.
layer as well as other thinner permanent substitutes do not have statistically signicant numbers
that prove a morphological result that is similar to
the double layer: immediate skin grafting is in fact
possible when using single layer dermal substitute
with adequate graft take percentages [52].
In addition to the type of product applied, to
ensure complete engraftment of the dermal substitute, we must adopt the same care and technique applied for skin grafts.
Positioning technique rst includes the measurement of the recipient wound bed: these
measurements will equate to the size of the DS
graft. Vascularization and complete debridement of the wound bed are necessary steps for
successful engraftment, as well as correct hemostasis to avoid any uid collection that will hinder graft take. The DS is then carefully placed
onto the recipient bed, dermis side down, and
secured with staples or sutures: It is crucial to
release the graft’s central tension by stapling or
suturing it to the middle of the recipient site, in
order to avoid the “sail effect,” especially if this
area is too wide and requires multiple DS sheets.
The aim is to achieve the best possible adhesion between the dermal substitute and the wound.
For this purpose, for curved surfaces we prefer to
use a negative pressure vacuum positioned onto
the dermal substitute for approximately 5days, in
order to keep the graft in place and adhered to the
bottom. It is also important not to let the dermal
substitute protrude from the wound but anchor it
in a way that the walls of the wound are also covered vertically by the dermal substitute.
There is no consensus on the type of dressing to
be applied above but it would be important to indicate the correct characteristics also to speed up dehospitalization and favor nursing care at the local
level. Generally, a compressive dressing is then
applied to avoid shear stress and damage of the
newly formed vessels: compression can be
obtained through tie over, polyurethane foams,
layered one on top of the other to add pressure, or
NPT that creates a pressure wound vacuum therefore granting complete adhesion to the wound bed.
Immobilization is another fundamental step:
DS sheets may be immobilized by stapling single
sheets one near the other, securing opposite trac-
24 Skin Substitutes
https://t.me/medicina_free
257
tion points rst and positioning a fatty gauze on
top to prevent the supercial layer from being
removed once the graft dressing is changed.
Finally, borders delimiting DS sheets must be
dressed with advanced antiseptic dressings such
as silver sulfadiazine, silver-based gauzes, betadine gel (Braunol; B.Braun, Milan, Italy); this is
because the edges represent the entry site for any
bacteria and microbes.
After approximately 3 weeks, DS is usually
ready to be covered by a skin graft that is commonly harvested with a dermatome.
Once the dermatome is assembled, the thickness of the split-thickness skin graft may be
selected by turning the dial on the side of the
dermatome.
According to the width of the guard, the length
of the graft to be harvested is calculated, based on
the total size of the skin graft desired. The length of
the donor site is then marked with a surgical marker.
Once the graft is harvested, it is placed in normal saline until it is to be used.
If desired, the split-thickness skin graft can be
meshed and the surgeon can perform this process
with a scalpel or a skin graft mesher. As previously described for DS positioning, skin grafting
positioning must also follow the same rules of
immobilization, compression and border dressing for a successful outcome.
An example of scalp reconstruction with dermal substitute (Integra double layer) and subsequent skin grafting can be observed in Figs.24.4,
24.5, 24.6, 24.7, 24.8, 24.9 and 24.10.
Dermal substitutes can be considered medical
devices or advanced therapy medicinal product,
depending on the specic composition, and
therefore complies with strict regulations that
vary from country to country.
According to the most recent regulations,
scaffolds made with isolated and/or puried animal or human-derived proteins are classied as
Fig. 24.5 First surgical operation: excision of the tumor
with skin layer, muscle and periosteum
Fig. 24.4 Preoperative markings: male patient with skin
cancer of the scalp
Fig. 24.6 Positioning of Integra® after skin cancer
removal
Соседние файлы в папке @xirurgi_2025