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 / Библиотека им академика М.И. Перельмана / Книга_1498_Библиотеки_им_академика_М_И_Перельмана.pdf
488
J.A. Cavallo et al.
to expand based on preclinical evidence that biologic materials enable
revascularization of soft tissue repair sites and improved pathogen
clearance in contaminated and infected surgical sites [
4, 5 ] , clinical
evidence that biologic materials do not necessarily require removal when
exposed or infected [
6– 8 ] .
Biologic Scaffolds for Abdominal Wall
Reconstruction
As the strength layer of the abdominal wall, fascial layers are
composed predominantly of fi broblasts and the extracellular matrix
components that these cells secrete: collagen, elastin, proteoglycans, and
fi bronectin. A high collagen and elastin content is responsible for the
great tensile strength and elasticity of fascia. The consistency of fascia is
determined by the total proteoglycan surface area, which is responsible
for binding cations and attracting water molecules. Fibronectins aid in the
attachment of cells to the extracellular matrix and therefore play an
important role in wound healing.
Biologic scaffolds composed of mammalian extracellular matrices
possess favorable characteristics for cell attachment, proliferation, and
differentiation and therefore serve as archetypal substrates for soft tissue
repair. The ideal biologic scaffold for abdominal wall reconstruction
closely resembles the native extracellular matrix of the host tissue,
possesses biomechanical properties that approximate the dynamics of the
abdominal wall, gradually degrades to allow for neovascularization and
high-integrity host tissue regeneration, avoids a biologic footprint that
could elicit a chronic in fl ammatory immune response and fi brosis from
the host, resists new infection and optimizes pathogen clearance from
contaminated and infected surgical sites, and provides an effective and
durable soft tissue repair. Biologic grafts used in abdominal wall soft
tissue repair are mostly porous acellular extracellular matrix constructs
from dermal, fascial, pericardial, or intestinal submucosal tissue of
cadaveric human, porcine, or bovine origin (Table 44.1 ). The characteristics
of the native species, donor, and tissue type of the scaffold determine the
remnant three-dimensional protein infrastructure following proprietary
manufacturing processes to decellularize, enhance, and sterilize the
material for clinical use. Some remaining source growth factors remain in
the scaffold and serve as chemotactic signals for host fi broblasts and
endothelial cells after implantation. The gradual degradation of the
489
44. Biologic Mesh: When and Why—A Critical Appraisal
Table 44.1. Biologic scaffolds for abdominal wall reconstruction.
Product Manufacturer Source Cross-linking process
Sterilization
process
Storage/
shelf-life Cost/cm
2
Xenografts
Biodesign™
Surgisis
®
and
Biodesign™
Surgisis
®
FM
Hernia Grafts
Cook
®
Medical
(Bloomington, IN)
Porcine small
intestine
submucosa;
FM = fenestrated
matrix
Ethylene oxide Room
temperature/
18 months
$10–20
CollaMend™ and
CollaMend™
FM Implants
Davol, Inc./C. R. Bard
(Warwick, RI)
Porcine dermis;
FM = fenestrated
matrix
1-Ethyl-(3-
dimethylaminopropyl)-
carbodiimide
hydrochloride (EDC)
Ethylene oxide Room temperature $10–20
Peri-Guard
®
Repair
Patch
Synovis
®
Surgical
Innovations
(St. Paul, MN)
Bovine pericardium Glutaraldehyde Ethanol, propylene
oxide, sodium
hydroxide
Room temperature <$10
Permacol™
Surgical
Implant
Covidien Surgical
(Norwalk, CT)
Porcine dermis Hexamethylene diisocya-
nate (HDMI)
Gamma irradiation Room temperature $20–30
Strattice™
Reconstructive
Tissue Matrix
LifeCell Corporation
(Branchburg, NJ)
Porcine dermis Electron beam
irradiation
Room temperature $20–30
SurgiMend
®
Collagen
Matrix
TEI Biosciences, Inc.
(Boston, MA)
Fetal bovine dermis Ethylene oxide Room
tempera-
ture/3 years
$20–30
(continued)
490
J.A. Cavallo et al.
Table 44.1. (continued)
Product Manufacturer Source Cross-linking process
Sterilization
process
Storage/
shelf-life Cost/cm
2
Veritas
®
Collagen
Matrix
Synovis
®
Surgical
Innovations
(St. Paul, MN)
Bovine pericardium Sodium hydroxide,
electron beam
irradiation
Controlled room
temperature
$20–30
XenMatrix™
Surgical Graft
Davol, Inc./C. R. Bard
(Warwick, RI)
Porcine dermis Electron beam
irradiation
Room temperature $20–30
Allografts
AlloDerm
®
Regenerative
Tissue Matrix
LifeCell Corporation
(Branchburg, NJ)
Human dermis Aseptically
processed
Freeze-dried,
refrigerated/
2 years
³ $30
AlloMax™
Surgical Graft
Davol, Inc./C. R. Bard
(Warwick, RI)
Human dermis Tutoplast
®
process,
low-dose
gamma
irradiation
Room temperature ³ $30
FlexHD
®
Acellular
Dermis
Musculoskeletal
Transplant
Foundation/
Ethicon, Inc.
(Somerville, NJ)
Human dermis Aseptically
processed;
passes U.S.
Pharmacopeia
Standard 71 for
sterility
Room temperature ³ $30
Data compiled from the manufacturer-provided instructions for product use, the International Consensus expert working group on acellular
matrices for soft tissue repair [
9 ] , and Deeken et al. [ 26 ]
491
44. Biologic Mesh: When and Why—A Critical Appraisal
biologic scaffold by host macrophages and matrix metalloproteinases
(MMPs) allows for simultaneous tissue remodeling through in fi ltration of
host cells, neovascularization, and regeneration of the dynamic
extracellular matrix. A semiquantitative histologic scoring system for
biologic scaffold tissue remodeling has been described on the basis of six
characteristics: cellular in fi ltration, cellular types present, host extracellular
matrix deposition, scaffold degradation, fi brous encapsulation, and
neovascularization (Table 44.2 ). Biologic scaffolds possess varying
degrees of biocompatibility and biodegradability based on their resulting
molecular composition and can therefore have substantial impact on the
host tissue response, the constructive remodeling of the substrate tissue,
and the integrity of the tissue repair.
Modi fi cations During Manufacture
During manufacture into biologic scaffolds, mammalian extracellular
matrices undergo a variety of chemical and mechanical processes to
render the scaffold free of immunogenic agents and safe for therapeutic
application: decellularization, sterilization, and preservation for storage.
Ideally, manufacturing processes should achieve these objectives while
minimizing disruption to the native scaffold structure. The molecular
structures of the extracellular matrix components are conserved across
animal species and demonstrate immunologic tolerance as allografts and
xenografts [ 9 ] . Manufacturing processes that alter the molecules of the
native scaffold may lead to more rapid in vivo degradation of the scaffold,
in fl ammatory cell response, and fi brotic encapsulation preventing
cellular in fi ltration and neovascularization, thus ultimately favoring scar
formation rather than constructive tissue remodeling in the host [ 10 ] .
Detergents used to extract cells and antigenic agents from the scaffold
have the ability to deform collagen and negatively impact the mechanical
properties of the scaffold [ 11 ] . For Food and Drug Administration (FDA)
clearance of all xenographic scaffolds, the products must be sterilized to
reduce the risk of infectious disease transmission. Chemical sterilization
with glutaraldehyde or ethylene oxide may leave residual by-products
that elicit an in fl ammatory response and alter the mechanical properties
of the scaffold, whereas radiation sterilization may disrupt the native
scaffold architecture, cause unintended molecular bonding, and alter the
mechanical properties of the scaffold [ 9, 11, 12 ] . Materials that remain
hydrated during storage tend to evacuate soluble growth factors, while
scaffolds that are preserved in dehydrated form can develop ultrastructural
492
J.A. Cavallo et al.
Table 44.2. Semiquantitative histologic scoring system of tissue remodeling characteristics for explants of biologic scaffolds.
Score 0 1 2 3
Cellular in fi ltration Zero cells in contact with
scaffold
Cells contact periphery,
no penetration into
scaffold
Cells in fi ltrate scaffold, but
none reach center
Cells penetrate into
center of scaffold
Cell types (“in fl ammatory
cells” include
neutrophils, mac-
rophages, and foreign
body giant cells)
In fl ammatory cells present,
no fi broblasts
Primarily in fl ammatory
cells, few fi broblasts
Primarily fi broblasts, few
in fl ammatory cells
Fibroblasts only, no
in fl ammatory cells
Host extracellular matrix
deposition
No host ECM deposition Host ECM deposited at
periphery of scaffold
Host ECM deposited inside
scaffold, but not at the center
Host ECM deposited
inside scaffold,
including the center
Scaffold degradation Original scaffold intact,
borders clearly
demarcated
Scaffold partially
degraded, layers
separated by cells,
blood vessels, host
tissue, etc.
Scaffold extremely degraded,
dif fi cult to distinguish
scaffold from host tissue
Scaffold completely
degraded, no
evidence of original
scaffold
Fibrous encapsulation Extensive encapsulation
(50–100% of periphery)
Moderate encapsulation
(25–50% of periphery)
Mild encapsulation (<25% of
periphery)
No fi brous
encapsulation
Neovascularization Zero blood vessels present Vessels present at
scaffold periphery,
no penetration into
scaffold
Vessels in fi ltrate scaffold but
none reach center of scaffold
Vessels penetrate into
center of scaffold
Histologic scoring system of six characteristics of biologic scaffold tissue remodeling: cellular in fi ltration, cell type, extracellular matrix (ECM)
deposition, scaffold degradation, fi brous encapsulation, and neovascularization. Note that higher scores indicate more favorable remodeling char-
acteristics of the biologic scaffold
(From ref. [
24 ] , with permission)
493
44. Biologic Mesh: When and Why—A Critical Appraisal
collapse, unintended molecular bonding, and restricted cellular in fi ltration
[ 8, 13 ] . Manufacturing processes have also been shown to greatly affect
the macrophage pro fi le of the host response and the pathway to
constructive remodeling versus chronic in fl ammation and scar formation
[ 14 ] . Manufacturing processes, therefore, have the potential to produce
direct effects on the durability of the tissue repair and the clinical
treatment outcomes. Many of these processes remain proprietary,
deterring further scienti fi c investigation of their potential impact on
clinical outcomes.
Collagen Cross-linking
Collagen cross-linking processes create bonds between collagen triple
helices intending to stabilize the scaffold and reduce enzymatic degradation
by MMPs. Often, these processes do not confer control over the degree of
collagen cross-linking, create short and in fl exible bonds that restrict early
cellular in fi ltration, or leave residual chemical by-products that elicit an
in fl ammatory response [ 10, 11, 15, 16 ] . Various degrees of collagen cross-
linking may also occur as an unintended consequence of other proprietary
manufacturing processes. The clinical bene fi t of cross-linked collagen
scaffolds remains to be proven. Preclinical studies by Deeken et al. have
demonstrated no signi fi cant difference in the tensile strength [ 17 ] of the
surgical repair site (Fig. 44.1 ) and earlier cellular in fi ltration, extracellular
matrix deposition, and neovascularization in non-cross-linked materials
compared to cross-linked materials explanted from a porcine model of
ventral hernia repair. However, by 12 months postimplantation, cross-linked
and non-cross-linked explants demonstrated no signi fi cant differences in
cell types, cellular in fi ltration, scaffold degradation, extracellular matrix
deposition, fi brotic encapsulation, or neovascularization [ 18, 19 ] (Fig. 44.2 ).
Further investigation of the comparative clinical effectiveness of cross-
linked and non-cross-linked materials is warranted.
Scaffold Fenestration
A host in fl ammatory cell response to a biologic scaffold may elicit
fi brotic encapsulation of the graft leading to a reduction in both in fi ltration
of host cells and neovascularization. The resulting dead space at the
graft-tissue interface may lead to increased clinical incidence of seromas,
wound complications, and infections [ 20– 23 ] . Fenestrated grafts that
494
J.A. Cavallo et al.
495
44. Biologic Mesh: When and Why—A Critical Appraisal
allow the passage of fl uid and the deposition of host tissue through pores
have been proposed as one potential solution. Preclinical studies by
Matthews et al. have demonstrated increased tissue incorporation at
fenestrated sites compared with nonfenestrated grafts up to 6 months
postimplantation in a porcine model of ventral hernia repair [
24, 25 ]
(Fig. 44.3 ). Conclusive long-term clinical studies comparing the clinical
effectiveness of commercially available fenestrated and nonfenestrated
scaffolds are lacking.
De Novo Scaffold Properties
The de novo biomechanical, thermal, and degradation properties of
12 biologic scaffolds FDA-approved for abdominal wall reconstruction
applications were recently evaluated [ 26 ] . Thermal analysis using
modulated differential scanning calorimetry demonstrated signi fi cantly
higher melting temperatures for cross-linked bovine pericardium and
porcine dermis compared to their non-cross-linked counterparts.
Degradation by collagenase digestion assay revealed signi fi cantly
longer resistance to enzymatic digestion by cross-linked bovine
pericardium compared to non-cross-linked bovine pericardium. The
suture retention strengths for all 12 scaffolds exceeded the threshold
value of 20 N suggested for hernia repair applications [ 27, 28 ] (range
23.75–127.20 N), with cross-linked materials generally exhibiting lower
suture retention strengths than non-cross-linked materials. The tear
resistance for only 6 of the 12 scaffolds exceeded the threshold value of
Fig. 44.1. Biomechanical properties of cross-linked and non-cross-linked
biologic scaffolds explanted from a porcine model of ventral hernia repair.
Biomechanical characteristics of mesh-repaired sites over time compared with
de novo strength and native porcine abdominal wall: ( a ) maximum load (Newtons
[N]), ( b ) tensile strength (N/cm), and ( c ) stiffness (N/mm). All four meshes were
signi fi cantly stronger and stiffer at time 0 compared with their corresponding
repair sites (mesh-abdominal wall tissue composites) after 1, 6, or 12 months
( p < 0.01 for all comparisons). Although signi fi cant differences were observed
between the strength and stiffness for each of the four meshes at time 0, no
signi fi cant differences in strength or stiffness were observed between mesh-
repair sites at 1, 6, or 12 months due to the type of mesh used to repair the defect
( p > 0.05 in all cases). In addition, no signi fi cant differences in strength or
stiffness of the repair sites were detected over time for any of the meshes studied
( p > 0.05 in all cases). Abd = abdominal (From ref. [
19 ] , with permission).
496
J.A. Cavallo et al.
20 N suggested for hernia repair applications [ 27, 28 ] (range 10.10–
84.73 N), with cross-linked materials exhibiting signi fi cantly lower tear
resistance strengths than non-cross-linked materials. The uniaxial
tensile strength was signi fi cantly greater for cross-linked compared to
non-cross-linked bovine pericardium. The ball burst strength of all 12
scaffolds exceeded the 50 N/cm threshold suggested for hernia repair
applications [ 27, 28 ] (range 66.2–1028.0 N/cm), and 9 of the 12 scaffolds
exhibited ball burst strain within the physiologic range of 10–30%
suggested for hernia repair applications [ 27, 28 ] (range 5.85–26.22%).
Cross-linked materials generally exhibited signi fi cantly lower ball burst
strengths compared to non-cross-linked materials. No clear trends were
Fig. 44.2. Tissue remodeling characteristics of cross-linked and non-cross-
linked biologic scaffolds explanted from a porcine model of ventral hernia repair.
Histologic scores, separated by mesh type and length of time in vivo: ( a ) cellular
in fi ltration scores, ( b ) cell type scores, ( c ) extracellular matrix (ECM) deposition
scores, ( d ) scaffold degradation scores, ( e ) fi brous encapsulation scores, and
( f ) neovascularization scores (From ref. [
19 ] , with permission).
497
44. Biologic Mesh: When and Why—A Critical Appraisal
otherwise noted between cross-linked and non-cross-linked materials,
suggesting the potential role of source factors and other proprietary
manufacturing processes.
Appropriate and Inappropriate Indications for Use
Graded Risk for Postoperative Surgical Site
Occurrence
As an instrument to assist surgeons in stratifying the risk of a postopera-
tive surgical site occurrence (SSO) after abdominal wall reconstruction,
the Ventral Hernia Working Group (VHWG) developed a novel grading
Fig. 44.3. Tissue remodeling characteristics of fenestrated and nonfenestrated
biologic scaffolds explanted from a porcine model of ventral hernia repair.
Histologic scores of biopsies at the fenestration sites of a fenestrated cross-linked
porcine dermal matrix (FM) compared to biopsies of a nonfenestrated cross-
linked porcine dermal matrix (NFM) explanted after 6 months from a porcine
model of ventral hernia repair: cellular in fi ltration scores, cellular type scores,
extracellular matrix (ECM) deposition scores, scaffold degradation scores,
fi brous encapsulation scores, and neovascularization scores [
25 ] .