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DOI 10.1007/s10029-013-1206-4
ORIGINAL ARTICLE
Received: 12 January 2013 / Accepted: 12 December 2013 / Published online: 27 December 2013
Springer-Verlag France 2013
Abstract
Purpose Although meshes reduce abdominal hernia
recurrence, they increase the risk of inflammatory complications. This study aimed to compare the early and late
postoperative inflammation and collagen deposition
responses induced by three meshes.
Methods Rats were allocated into three groups. In group
I, a polypropylene (PP) mesh was implanted in the
abdominal wall. In groups II and III, PP ? polyglactin
(PP ? PG) and PP ? titanium (PP ? TI) meshes were
employed, respectively. On the seventh (7th) postoperative
day, collagen deposition and inflammation were evaluated,
and immunohistochemistry was performed on abdominal
wall biopsies. These data were compared with those
obtained on the fortieth (40th) postoperative day in a previous study.
Results The early inflammatory responses were the same
in all groups. With time, it decreased in group I
(p = 0.047) and increased in group II (p = 0.003). Group I
exhibited early elevated VEGF (p \ 0.001), COX2
(p \ 0.001), and collagen (p = 0.023) levels, and group II
exhibited the most severe inflammatory tissue response. On
the 40th postoperative day, the VEGF (p \ 0.001) and
Introduction
Cytokines are synthesized by injured tissue to modulate the
inflammatory cascade during the initial phase of repair in the
abdominal wall [1]. Cytokines are fundamental to cell proliferation, the extracellular matrix, and collagen synthesis [2].
Meshes were developed due to the high rate of recurrence after hernia surgery with primary sutures, and mesh
application in abdominal wall repairs has reduced the
recurrence indexes from over 50 % to approximately 10 %,
particularly in ventral hernias [3]. Although meshes are the
most commonly used biomaterials in medical practice,
with approximately 1.5 million implants used per year [4],
numerous questions remain about the host inflammatory
response induced by mesh implants [310]. Despite the
frequent use of mesh implants, there remains no consensus
regarding their classification and nomenclature [11].
Polypropylene (PP) is the most commonly material
used to manufacture meshes, but other absorbable and
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non-absorbable materials are also used [11, 12]. Theoretically, the increased diameter of the pores and the
reduction in the density of meshes could minimize
inflammation and, therefore, the complications related
to this implant [8]. However, several studies have
reported conflicting results, including reports of the
reduction of early complications and reports of a possible increase in recurrences [1318]. Unexpected
complications, such as the reduced sperm mobility in
response to lightweight mesh implanted in the inguinal
region [17] and mechanical failure with fracture of a
lightweight mesh in the surgical repair of a recurrent
median ventral hernia [18], have been reported.
Klinge et al. [11] evaluated the indications for explanting mesh implants in 1,000 cases. Infection was the main
reason for removing small pore PP meshes, which were
prevalent in the reviewed data. Hernia recurrence was the
main reason for explanting large-pore meshes [11].
Pascual et al. [19] observed that an intense inflammatory
reaction was related to the presence of absorbable material;
additional characteristics include low expression of growth
factors, worse collagen deposition, and worse mesh integration in host tissue [19].
Some authors have studied mesh modified with a coating film or the use of various substances, including those
from hormonal sources, like aldosterone. Although these
authors shared the goals of reducing the formation of
adhesions or modulating the inflammatory process, e.g., the
action of mast cells, foreign body reactions, or fibrosis [12,
2022], their results are varied.
In a previous study, we assessed the serum, inflammatory response, and collagen deposition in rats on the
40th postoperative day after mesh implantation, including conventional PP, lightweight PP ? polyglactin
(PG ? PG), and lightweight PP ? titanium (PP ? TI).
Serum cytokines were similar in all groups. The heavyweight PP mesh belatedly induced the least inflammation
and improved collagen deposition. The PP ? PG mesh
was correlated with the most intense tissue inflammatory
response and low, irregular, and heterogeneous collagen
deposition. The PP ? TI mesh led to an intermediate
result [23].
The above results prompted further questions. The
results appear contradictory with respect to whether
collagen deposition depends on an inflammatory reaction. PP mesh belatedly induces a subdued inflammatory
reaction but leads to greater collagen deposition, which
is in direct contrast with the results observed for the
PP ? PG mesh. Would it be possible to demonstrate a
more intense early tissue inflammatory response with PP
mesh? Could the kind of inflammatory reaction induced
by the PP ? PG mesh be the key factor for the belated
inhibition of collagen deposition? Could the differences
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Methods
This research was an experimental study in which it was
employed an acute wound model, not a hernia model.
Thirty male adult Wistar rats weighing 250300 g were
randomly allocated into groups I, II and III. Each group
comprised 10 animals. An intraperitoneal injection of 10 %
ketamine hydrochloride and 2 % xylazine solution was
applied for anesthesia.
After a 4-cm longitudinal incision was made along the
animals flank, a fragment of the anterior abdominal
musculature measuring 2 cm2 (2.0 9 1.0 cm) was
removed. The mesh was positioned to replace the defect
that had been produced and was fixed by six PP 3-0
switches sutures. In group I, the mesh was made of
heavyweight monofilament PP and had small pores (Intracorp, Venkuri, Brazil). In group II, the mesh contained
large pores and was made of lightweight PP and an
absorbable material, PG (VyproII, Ethicon, USA). In
group III, a large-pore lightweight mesh made of PP and a
nonabsorbable material, TI, was used (Timesh, GfE,
Germany).
Group I, the group in which the animals were implanted
with the most commonly used type of mesh [11], was
considered the control group.
On the 7th postoperative day, the rats were killed by
means of a lethal dose of ketamine. A fragment was
removed from the central region of the prosthesis as far as
possible from the mesh stitches. The tissue sample was sent
for a histological inflammatory response analysis, including hematoxylin-eosin, Masson trichrome, and picrosirius
(under polarized light to assess collagen deposition), and
the immunohistochemical analysis of Vascular Endothelial
Growth Factor (VEGF-Dbs rabbit polyclonal antibody,
Santa Cruz Biotechnology, Inc.) and Cyclooxygenase 2
(COX2-rabbit polyclonal antibody, Spring Cold Spring
Harbor Laboratory, USA).
To objectively evaluate the tissue reaction and expression of VEGF and COX2, numeric scales were employed
[2325], and the scoring scales are presented in Tables 1,
2.
565
Legend
14 layers
59 layers
1030 layers
[30 layers
1
2
Results
3
4
D: Tissue maturation
1
Table 2 Numeric scales to value VEGF and COX2 imunohistochemistry expression in groups I (PP), II (PP ? PG) and (PP ? TI)
VEGF
COX2
% cells
Score
Intensity
Score
% cells
Score
Intensity
Score
025
Weak
025
2650
Moderate
2650
Weak
Moderate
5175
Strong
51100
Strong
76100
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Fig. 1 Boxplot
graph
that
demonstrates
the
sum
(S = A ? B ? C ? D) of the items related to inflammatory tissue
reaction on 7th and 40th postoperative days (PO) in groups I, II and
III, where A is the layer of cells on granulomas, B is the inflammatory
reaction in host tissue, C is the inflammatory response on the surface
of the mesh, D is the tissue maturation
Discussion
The main reason for the subject and the design of this
research was our need to continue investigating the questions raised in our previous study, in which conventional
PP mesh placement unexpectedly and belatedly resulted in
less tissue inflammation and increased late collagen deposition compared with PP ? PG and PP ? TI meshes.
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Fig. 4 Photomicrography (9100). Immunohistochemical analysis of COX2 (narrows) in groups I (PP), II (PP ? PG) and III (PP ? TI) on the
7th postoperative day. Observe mesh filaments (stars)
Fig. 6 Photomicrgraphy (940). Picrosirius demonstrates collagen deposition (narrows) on the 7th postoperative day in groups I (PP), II
(PP ? PG) and III (PP ? TI). Observe mesh filaments (stars)
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10.
11.
12.
13.
14.
15.
16.
17.
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