Hernia (2014) 18:221–230
DOI 10.1007/s10029-013-1076-9
ORIGINAL ARTICLE
Early report of a randomized comparative clinical trial
of StratticeTM reconstructive tissue matrix to lightweight synthetic
mesh in the repair of inguinal hernias
C. F. Bellows • P. Shadduck • W. S. Helton •
R. Martindale • B. C. Stouch • R. Fitzgibbons
Received: 19 January 2012 / Accepted: 8 March 2013 / Published online: 31 March 2013
Ó Springer-Verlag France 2013
Abstract
Purpose Biologic grafts are rarely used for inguinal
herniorrhaphy. The aim of this study was to compare the
clinical outcomes between patients undergoing a Lichten-
stein’s hernioplasty with a porcine mesh versus a standard
synthetic.
Methods A prospective, randomized, double-blinded
multicenter, evaluation of inguinal hernia repair was con-
ducted between 2008 and 2010. Lichtenstein hernioplasty
was performed using StratticeTM or lightweight polypro-
pylene (Ultrapro) mesh. Quality of life, pain, overall
complication rate, and recurrence were measured.
Trial Registration clinicaltrials.gov Identifier: NCT00681291.
C. F. Bellows (&)
Department of Surgery SL-22, Tulane University,
1430 Tulane Ave, New Orleans, LA 70115, USA
e-mail: cbellows@tulane.edu
P. Shadduck
North Carolina Specialty Hospital and Duke University,
Durham, NC, USA
W. S. Helton
Department of Surgery, Virginia Mason Medical Center,
Seattle, WA, USA
R. Martindale
Department of Surgery, Oregon Health Sciences Center,
Portland, OR, USA
B. C. Stouch
Department Biostatistics, The Philadelphia College of Medicine,
Philadelphia, PA, USA
R. Fitzgibbons
Department of Surgery, Creighton University, Omaha, NE, USA
Results One hundred and seventy-two patients were
randomized to StratticeTM (n = 84) or Ultrapro (n = 88).
At 3 months postoperatively, there were no differences on
the occurrence or type of wound events [RR: 0.98 (95 % CI
0.52–1.86, p = 0.69), StratticeTM (15 events) vs. Ultrapro
(16 events)]. The mean level of impairment caused by the
hernia, assessed by Activities Assessment Scale (AAS),
significantly decreased postoperatively in both groups at
3 months (31 % StratticeTM and 37 % Ultrapro). Patients
in the Strattice group reported significantly less postoper-
ative pain during postoperative days 1 through 3 compared
to Ultrapro patients. However, the amount of postoperative
pain at 3 months, as assessed by the mean worst pain score
on a visual analog scale and the Brief Pain Index, was
similar between groups (95 % CI 1.0–29.3). No hernia
recurrences were observed in either group.
Conclusions StratticeTM is safe and effective in repairing
inguinal hernia, with comparable intra-operative and early
postoperative morbidity to synthetic mesh. Long-term fol-
low-up is necessary in order to know whether the clinical
outcomes of Strattice are equivalent to standard synthetic
mesh in patients undergoing Lichtenstein’s hernioplasty.
Keywords Inguinal hernia
Biologic mesh

Porcine dermis matrix
Introduction
The repair of inguinal hernias is one of the most common
general surgical procedures with more than 90 % repaired
with a surgical mesh. A meta-analysis of 20 trials (5,016
participants) of open mesh versus non-mesh reported by the
EU Hernia Trialists Collaboration demonstrated a reduc-
tion in the risk of recurrence of between 50 and 75 % when
123
222
a prosthesis was used [1]. In fact, the routine use of pros-
thetic material for inguinal hernia repair has resulted in
such a significant decrease in the recurrence rate that
complications, most notably chronic groin pain, have now
emerged as the most pressing issue following inguinal
herniorrhaphy. The International Association for the Study
of Pain defines chronic groin pain as pain reported by the
patient beyond 3 months following inguinal hernia repair
[2]. Although the reported incidence varies widely in the
literature, most authorities agree that some long-term
chronic groin discomfort occurs in about 10 % of inguinal
herniorrhaphy patients and severely interferes with activi-
ties of daily living in one percent [3]. The most common
surgical meshes are made from plastic which incites an
inflammatory response, which often culminates in the
formation of a scar plate [4, 5]. It is likely that such scar-
ring contributes to the chronic groin pain following
inguinal herniorrhaphy.
In recent years, a new class of prosthetics used in a wide
variety of reconstructive applications have become popu-
lar. Made of animal and human products, these materials
consist of extracellular matrix, which has been stripped of
its cellular components. Unlike the synthetic plastic
meshes, they are believed to facilitate site-specific tissue
remodeling into the original host’s tissue, which can be
assessed histologically and functionally [6]. This ability to
be remodeled makes the new materials theoretically
attractive to surgeons as a means to reduce post inguinal
herniorrhaphy chronic groin pain. The aim of this study
was to evaluate the safety and efficacy of a porcine dermis
biologic prosthesis (StratticeTM Reconstructive Tissue
Matrix, LifeCell Corp, Branchburg, NJ, USA) when used
in a standard Lichtenstein’s hernioplasty by comparing it to
a commonly used lightweight polypropylene prosthesis
(Ultrapro, Ethicon, Somerville, NJ, USA). We realize that
there are many theoretical reasons why one would not
consider a biologic for an inguinal hernia not the least of
which is cost. However, the mechanism of action of the
biologics, that is, remodeling to human tissue, could pos-
sibly have such a dramatic effect primarily as it relates to
chronic groin pain that we felt it was worthwhile at least
studying. In this paper, we report the early results (3-month
follow-up) of a prospective, multicenter, randomized clin-
ical trial (NCT00681291) designed to test the hypothesis
that a biological prosthesis results in better hernia-specific
quality of life and less chronic pain when compared to a
plastic prosthesis.
Methods
A prospective, randomized, controlled, third-party-blinded
multicenter, interventional trial was designed by four
123
Hernia (2014) 18:221–230
surgeons. Early in the study development, collaboration
with the LifeCell Corporation was established because the
biological prosthesis that we thought would be best suited
for this trial was manufactured by that company (Strat-
ticeTM). The company agreed and became the major
funding source for the trial. The details of this collabora-
tion along with the extensive measures built into the trial to
try to prevent bias because of the industry relationship have
been published previously [7]. The study objective is to
compare StratticeTM to a lightweight polypropylene mesh
(Ultrapro) using the Lichtenstein tension-free hernioplasty
method. We wanted to determine whether male patients
will have superior outcomes following elective unilateral
inguinal hernia repair with StratticeTM compared to those
repaired with Ultrapro. The primary endpoint was
resumption of activities of daily living (ADL) at 1-year
follow-up. Secondary outcome measures include long-term
pain, postoperative complications, and incidence of recur-
rence. Chronic pain was defined as persistent groin pain or
any groin discomfort affecting daily activities that did not
disappear by 3 months after surgery. The Local Ethics
Committees at all participating hospitals approved the
study. The CONSORT Statement for reporting a random-
ized trial is followed according to applicability (www.
consort-statement.org).
Study materials
StratticeTM reconstructive tissue matrix
(LifeCell Corp., Branchburg, NJ)
This is a non-crosslinked biologic prosthesis derived from
porcine dermis and processed to remove hair, cells, and cell
components as well as other antigens present in the matrix. It
behaves like a natural scaffold for tissue remodeling by the
host until it is completely substituted by the host’s mature
and newly formed tissue, theoretically making it more
physiologic than synthetic prostheses [6]. At the same time,
it possesses an initial strength that is supraphysiologic and
therefore is a suitable prosthesis for abdominal wall recon-
struction while the remolding process is taking place [8].
Ultrapro (Ethicon, Somerville, NJ)
UltraproTM is a lightweight partially absorbable macropo-
rous mesh consisting of approximately equal parts of
absorbable poliglecaprone-25 monofilament fiber (Mon-
ocrylTM) and nonabsorbable polypropylene monofilament
fiber (ProleneTM). After absorption of the poliglecaprone-
25 component, only the polypropylene mesh remains. It is
indicated for use in the repair of hernias or other abdominal
defects and has been successfully used in open inguinal
hernia repair [9].
Hernia (2014) 18:221–230
Repair technique
A tension-free hernioplasty technique (i.e., Lichtenstein
Hernioplasty) was performed for all patients using a
prosthesis, approximately 8 9 15 cm, tailored in situ. A
detailed description of the surgical technique employed has
been previously described [7].
A smaller size for this biological prosthesis is expected
because it provides minimal elasticity and is a contiguous
sheet as apposed to the mesh material with its multiple
macro pores making the size variable related to the stretch
or lack thereof applied by the surgeon and the amount of
material ‘‘bunched’’ into the sutures at the edges. Briefly,
after making the skin incision, the inguinal canal is
exposed by opening the aponeurosis of the external oblique
muscle through the external ring. A large space is then
created beneath the external oblique aponeurosis by blunt
dissection from the anterior superior iliac spine laterally to
a point 2 cm medial to the pubic tubercle medially to
eventually accommodate either prosthesis. Next, the sper-
matic cord is mobilized. In patients with an indirect hernia,
the sac is mobilized high and reduced without ligation
whenever possible. The prosthesis is sutured to the internal
oblique abdominal muscle, the rectus sheath, and the
shelving edge of the inguinal ligament. The tails of the
mesh are drawn equally around the cord, and the inferior
edge of each tail is sutured to the inguinal ligament. For the
StratticeTM, the tail was slit from its inferior edge to
accommodate the spermatic cord [7]. For patients ran-
domized to Ultrapro, the mesh is slit laterally and the tails
thus created positioned around the base of the cord struc-
tures with the superior tail overlapping the inferior tail. The
inferior surfaces of the two tails are sutured together and to
the inguinal ligament just lateral to the internal ring
forming a type of shutter valve around the cord. Closure of
the aponeurosis of the external oblique abdominal muscle
is performed by continuous suture, leaving the spermatic
cord in its natural subfascial position. Finally, the skin is
sutured and the length of the skin incision measured. Early
mobilization as soon as possible after surgery, including
drinking and eating, is allowed and advised. Although
StratticeTM Tissue Matrix is available in two versions
(Pliable and Firm), the more flexible one (Pliable) was used
for this study. Interestingly, the initial biomechanical
strength of each version is essentially the same, but the
handling properties are slightly different. As a result, both
types of Strattice were used by the principle investigators
in an inguinal hernia cadaver laboratory prior to the start of
the trial. Results from this blinded experiment demon-
strated that 100 % of the investigator preferred StratticeTM
Tissue Matrix Pliable because it was more flexible and
easily contoured to the dissected inguinal space compared
223
to the StratticeTM Tissue Matrix Firm that was felt to be too
rigid.
Inclusion and exclusion criteria
All adult males greater or equal to 18 years of age with a
primary non-emergent inguinal hernia were eligible to
participate. Exclusion criteria included patients with
recurrent hernias, any condition preventing a correct
evaluation of pain (preexisting chronic pain syndrome,
active pain management, known drug abuser, or significant
psychiatric disorder), hypersensitivity to any drug in study,
and patients with intra-operative findings of different
pathology.
Primary endpoint
Resumption of activities of daily living (ADL) as measured
by the Activities Assessment Scale (AAS) [10] was
selected as the primary endpoint. The AAS is a 13-item
tool of graded-intensity activities designed to specifically
measure patient functioning after hernia surgery. It was
developed for two randomized clinical trials, one evaluat-
ing laparoscopic versus open hernia repair procedures and
another comparing watchful waiting versus routine ingui-
nal herniorrhaphy. It has been demonstrated to be a reli-
able, valid, and a clinically responsive instrument. It is easy
to administer and requires less than 5 min of patient time to
complete. The validity and reliability of the AAS have
been previously demonstrated, and results show substantial
correlation with the physical function subscale of the SF-36
[10].
Data collected
Preoperative data included patient demographics, occupa-
tion, and comorbidities. Pain was measured using two
different pain-rating scale systems: a 10-point scale
(responses range from 0 = ‘‘no pain’’ to 10 = ‘‘worst pain
imaginable’’), and the Brief Pain Inventory (BPI) ques-
tionnaire (severity and interference); the pain level was
assessed at each clinic visit. Each time the patient com-
pleted the BPI pain questionnaire; he or she was also asked
to shade the location of pain on a body diagram [11].
Intra-operative details were recorded and included, the
length and width of the mesh, type of hernia defect,
duration of the procedure, estimated blood loss and any
injuries to nerves, cord, etc. Patients were scheduled to
return for clinical follow-up at 10 days, 3 months, 1- and
2-year after surgery. Postoperative data collection includes
the following: length of hospital stay, seroma formation,
pain evaluation, wound infection, recurrence, and other
123
224
complications. A recurrence suspected by clinical exami-
nation requires confirmation by ultrasonography.
Statistical methodology
Assuming a 20-point improvement in the AAS over base-
line and a 10-point difference between the StratticeTM and
Ultrapro groups, setting a at 0.05 and b at 0.8 with a
2-sided test, the sample size for each arm was 74 subjects.
Assuming a 15 % loss to follow-up over the 2-year study,
the recruitment target was set at 170. An independent
biostatistician performed data review and statistical anal-
ysis. The results were analyzed using SPSS version 13.0
(Chicago, IL, USA) using chi square and Fisher’s exact
tests for proportions as appropriate. Student’s t test and
Mann–Whitney U test were used, respectively, to deter-
mine means of the independent samples for data both
normally and non-normally distributed (the data were
previously tested for normality using the Kolmogorov–
Smirnov test). p \ 0.05 was considered statistically sig-
nificant. All analyses were conducted on the ITT popula-
tion without imputation. The ITT population was the
primary population pre-specified for analysis of this study.
For examination of the pain trajectory over the initial
10 days following the surgery, we believe that this is the
appropriate population for examination of this endpoint.
Patients in the Per Protocol population who withdrew prior
to 24 months due to failing health or relocation are not
related to the study surgery. Removing these patients from
the 10-day analysis of postoperative pain would not pro-
vide any greater insight beyond the complete ITT
population.
Randomization and blinding
A 1:1 randomization (StratticeTM: Ultrapro) was per-
formed. Patients were randomly allocated at each hospital
to undergo either Lichtenstein’s operation with either
Ultrapro or StratticeTM. Randomization was performed by
way of computer-generated schedule, and the results were
sealed in numbered envelopes. The envelope was opened
intraoperatively after it was established that there were no
exclusion criteria. Apart from the surgical team, no one
knew which type of prosthesis was used. This information
was not given to patients, their family or friends or their
referring doctors. The surgeon was, of course, technically
un-blinded but they were asked not to review their opera-
tive notes prior to seeing the patients for their follow-up
study appointments. All postoperative visits included
evaluation by a blinded third-party heath care provider who
was unaware of the patient’s randomization. This individ-
ual was responsible for filling out the case report forms.
The patient and third-party evaluator were blinded to which
123
Hernia (2014) 18:221–230
mesh was implanted for the entirety of the study. Patients
will be informed of what type of mesh was implanted only
after all patients have completed their 2-year review.
Follow-up
Planned data analyses were scheduled for month 3, 12, and
24 data collection time points. All patients have now
completed their 3-month assessments. In this paper, we
report the 3-month data and assess early complications or
hernia recurrence. The same pain and Quality of life (i.e.,
ADL) evaluations were performed during the entire follow-
up period. Total analgesic drug requirements were recorded
for each patient and considered a measure of analgesic use.
Patient satisfaction with the surgery was also recorded on
follow-up.
Results
In this ongoing, 24-month, prospective, double-blind ran-
domized, multicenter study, 172 men underwent open
repair of primary unilateral, non-incarcerated inguinal
hernias using StratticeTM (n = 84) or Ultrapro (n = 88).
Patient enrollment in the study began February 1, 2008 and
ended on February 17, 2010. A total of 185 subjects were
consented to participate and 172 were enrolled. At
3 months, 2 were lost to follow-up in the StratticeTM group.
Patient demographics and baseline characteristics are
summarized in Table 1. Of note, there was no significant
difference in the baseline (preoperative) Activity Assess-
ment Scores (AAS) or pain scores (VAS, BPI) between the
two groups. To date, there have been 94 protocol devia-
tions; nine were recorded preoperatively, 20 at the time of
operation, and the remainder in follow-up. The deviations
are listed in Table 2. Not collecting a sample for C-reactive
protein assessment at the time of operation or in follow-up
accounted for 57 % of the deviations.
Ninety-six hernia repairs (56 %) were performed under
local anesthetic usually with intravenous sedation
(Table 3). The other 44 % had their operations under
general anesthesia but local anesthesia was injected at the
end of the operation to decrease immediate postoperative
pain (Table 3). All hernias were primary and unilateral, as
dictated by the protocol, and 55 % were right sided
(Table 3). The most common hernia type was indirect
(54 %) followed by direct (31 %), pantaloon (14 %), and
other (1 %). The average mesh size for the Ultrapro group
(103.6 ± 38.5 cm2) was slightly larger than the Strattice
group (84.5 ± 26.7 cm2, p = 0.002). The mean surgical
time was less in the Ultrapro group (64 ± 22.0 min)
compared to the Strattice group (74.0 ± 30.5 min;
p = 0.02). Surgery times for 51/84 StratticeTM patients
Hernia (2014) 18:221–230 225

Table 1 Preoperative patient characteristics Table 3 Operative characteristics, according to mesh group
TM TM
Variable Strattice Ultrapro p value Characteristic StratticeTM UltraproTM p value
(n = 84) (n = 88)
Anesthesia
Age (mean ± SD, years) 56 ± 15 57 ± 14 0.73 General 17 23 0.37*
BMI (mean ± SD, kg/m2) 25.9 ± 3.9 26.2 ± 3.3 0.52 Local 46 50
Occupation types [n (%)] General ? local 21 15
Construction worker 11 (13) 13 (15) 0.50 Location
Clerical/profession 29 (35) 30 (34) Right 40 55 0.07*
Self-employed 10 (12) 15 (17) Left 44 33
Student 2 (2) 0 (0) Mesh size (cm2) 84.5 ± 26.7 103.6 ± 38.5 0.002
Retired 21 (25) 24 (27) Intra-operative blood loss 18.4 ± 30.8 19.2 ± 56.2 0.9
Unemployed 11 (13) 6 (7) (ml)
Highest level of activity [n (%)] Operative times (min) 74.0 ± 30.5 64.2 ± 22.0 0.02
Light work 20 (24) 17 (19) 0.95 *Probability value derived from the 2-tailed Fisher’s exact test
Medium work 21 (25) 21 (24)
Heavy work 25 (30) 30 (34)
Very heavy work 10 (12) 11 (13) Table 4 Intra-operative events, according to mesh group
ASA classification StratticeTM Ultrapro p value
Healthy (I) 47 (56) 52 (59) 0.57
Excessive bleeding (yes) 1 0 0.49
Mild systemic (II) 32 (38) 28 (32)
Injury to bowel (yes) 0 1 1.0
Severe systemic (III) 5 (6) 8 (9)
Injury to bladder (yes) 0 0 NC
Time since discovery of 570 ± 1,007 642 ± 1,349 0.69
hernia (days) Injury to vas deferens (yes) 1 0 0.49
Activities Assessment 31.5 ± 14.3 34.7 ± 16.2 0.18 Hernia sac opened (yes) 18 18 1.0
Scale (AAS) score Hernia sac repaired (yes) 13 13 1.0
Brief Pain Inventory 7.6 ± 7.7 7.1 ± 7.6 0.68 Nerve cut (yes) 21 11 0.05
Composite Index Nerve buried (yes) 16 9 0.13
VAS pain score 2.6 ± 2.6 2.8 ± 2.7 0.19 Injury to vascular structure (yes) 0 0 NC
Current smoker (yes) 65 75 0.17 Anesthetic complication (yes) 0 0 NC
CRP level (mg/dl) 0.49 ± 0.7 0.47 ± 0.8 0.88
NC not calculated

Table 2 Protocol deviations

Preoperative
Screening/baseline activities were performed prior to obtaining
informed consent
Patient randomized that met exclusion criteria
Intra-operative
C-reactive protein levels not obtained day of surgery
Clinical site staff deviated from the study randomization plan
Postoperative
C-reactive protein levels not obtained at day 10
C-reactive protein levels not obtained at 3 months
Patient did not attend the postoperative day 10 visit
Patient did not attend the 3-month visit
Patient did not complete the Pain Diary
exceeded 90 min (p = 0.19). The most common reason
n recorded for prolonged operative times was the presence of
a very large ‘‘adherent’’ hernia. Type and rate of intra-
6 operative complications (Table 4) were comparable
between groups.
3 Regarding the duration of hospitalization, there was no
difference between the two groups (0.06 ± 0.3 days
18 StratticeTM vs. 0.09 ± 0.4 days Ultrapro). Nine patients
2 (5.2 %) remained in hospital overnight because of a urinary
retention (3), postoperative hematoma (1), postoperative
12 pain (2), atrial fibrillation (1), or for social reasons (2).
24 Although approximately 80 % of patients were discharged
1 within 9 h after surgery, more patients stayed at the hos-
13 pital overnight in the Ultrapro group (n = 6) compared to
15 the StratticeTM group (n = 3).

Early complications (within 3 months)

(60.7 %) and 41/88 Ultrapro patients (46.6 %) exceeded
60 min (p = 0.07). Surgery times for 15/84 StratticeTM Complications reported at the first follow-up visit (10 days)
patients (17.9 %) and 9/88 Ultrapro patients (10.2 %) and at 3 months after surgery are shown in Table 4. At

123
226 Hernia (2014) 18:221–230

Table 5 Early Complications 3 months after surgery, according to Table 6 Postoperative scores (3 months after surgery) minus pre-
mesh group operative scores for the two concepts on the BPI short form,
according to mesh group
Postoperative event StratticeTM UltraproTM No. (%) p value
(within 3 months [n (%)] [n (%)] of all StratticeTM Ultrapro p value
of procedures) patients
AAS
Hematoma 7 (8) 5 (6) 12 (9) 0.560 Overall -9.9 ± 14.7 -12.7 ± 14.9 0.26*
Scrotal hematoma 2 (2) 6 (7) 8 (5) 0.279 \0.001**
Seroma 6 (7) 4 (5) 10 (8) 0.529 Sedentary -2.8 ± 5.2 -2.8 ± 4.5 0.98*
Infection 0 (0) 1 (1) 1 (1) 1.000 \0.001**
Orchitis 1 (1) 2 (2) 3 (1) 1.000 Ambulatory -2.7 ± 4.3 -3.1 ± 4.3 0.52*
Urinary retention 0 (0) 2 (2) 2 (1) 0.497 \0.001**
Hematuria 0 (0) 0 (0) 0 (0) NC Work/exercise -4.1 ± 5.6 -5.7 ± 6.0 0.10*
Dehiscence 0 (0) 0 (0) 0 (0) NC \0.001**
Hernia recurrence 0 (0) 0 (0) 0 (0) NC VAS/worst pain -1.9 ± 3.0 -2.0 ± 2.6 0.759
Total 16 (19) 20 (23) 36 0.579 in the last 24 h
NC not calculated BPI
Severity -5.3 ± 8.3 -5.2 ± 7.8 0.95*
\ 0.001**
3 months postoperatively, there were no statistical differ-
Interference -8.5 ± 21.0 -12.8 ± 21.2 0.22*
ences in the occurrence or type of wound events [RR: 0.98
\0.001**
(95 % CI 0.52–1.86, p = 0.69), StratticeTM (15 events) vs.
Ultrapro (16 events)]. The most common complication was * 1-factor analysis of variance: Strattice versus Ultrapro
hematoma, followed by seroma (Table 5). Overall, there ** Paired difference t test: analysis of the intra-patient paired changes
were 20 hematomas (8 scrotal and 12 wound, 19 treated from baseline to 3 months in the StratticeTM or Ultrapro groupTM
conservatively, and one requiring operative drainage) and
10 seromas in the first 3 months. All seromas (9 mild and 1 At 3 months postoperatively, 15.5 % of StratticeTM
moderate) resolved without intervention. Two patients in patients reported localized pain to the groin, compared to
the Ultrapro group had urinary retention. One superficial 22.7 % of the Ultrapro patients (p = 0.25).
wound infection was diagnosed in the Ultrapro group In the early postoperative period (0–10 days), patients
2 months after surgery, whereas no infection was reported were given a diary to record the type and quantity of pain
in the StratticeTM group. Infection was managed conser- medication consumed, along with the level of pain they
vatively with antibiotics without mesh removal. No hernia were experiencing at the time they took their pain medi-
recurrences have been reported. cation. The level of pain was recorded using a 6-point
multinomial scale that ranged from ‘‘No Hurt’’ to ‘‘Hurts
Primary outcome Worse’’. For each of the 10 days following the hernia
repair, the intra-patient pain score was averaged and
At 3 months, our analysis showed that the overall Activi- compared between the randomized treatment groups.
ties Assessment Score decreased after repair (Table 6) in Analysis of the intra-day cumulative dose of pain medi-
both groups. Preoperatively, the degree of impairment as cation did not differ between the randomized treatment
measured by the AAS was 34.7 ± 16.2 (Ultrapro) and groups. However, during the initial 3 days post-surgery,
31.5 ± 14.3 (StratticeTM) and decreased to 21.8 ± 7.6 and patients randomized to receive StratticeTM had less pain
21.7 ± 7.0, respectively, at 3 months postoperatively. compared to patients who received Ultrapro. As shown in
Importantly, there were no statistically significant differ- Fig. 1, during postoperative days 1 and 3, the comparison
ences between the two groups in terms of their overall AAS of the level of pain was significantly less in the Strattice
scores (sedentary, with ambulation, or with exercise) at group (p \ 0.05). The level of pain between the groups
3 months or in their mean change from baseline at varied slightly during postoperative days 7 through 10 but
3 months (Table 6). did not approach significance. Moreover, based on the
10-day diary, there was no significant difference between
Secondary outcomes Strattice and Ultrapro groups in the total number of pain
tablets taken (total number of tablets 21.4 ± 13.8 vs.
Preoperatively, 67 % of the patients randomized to receive 21.7 ± 17.1; p = 0.91).
StratticeTM, compared to 68 % of the patients who received The mean changes in the BPI 24-h average pain scores
Ultrapro (p = 0.87), reported localized pain in the groin. over time stratified by group are shown in Table 6. The BPI

123
Hernia (2014) 18:221–230 227

P=0.046 P=0.015 P=0.191 P=0.872 P=0.796

Day 1 Day 3 Day 5 Day 7 Day 9

Fig. 1 Postoperative (days 1, 3, 5, 7 and 9) patient pain scores from early on (day 1–3), patients who received StratticeTM had significantly
the subject diary (mean with 95 % CIs). The numeric pain rating was less pain; however, this difference dissipated over the remaining
entered using a 1–6 scale as specified on the case report form. Of note, 10-day period. *Data are ITT

Table 7 Satisfaction scores at 3 months
TM
Strattice Ultrapro
(mean ± SD) (mean ± SD)
Subject 9.5 ± 1.24 9.6 ± 0.83
Surgeon 9.7 ± 0.59 9.6 ± 0.68
is designed to assess both pain severity and interference
with functions caused by pain. In our study, we observed
that the patients in general reported lower intensities of
pain after hernia repair. Indeed, the pain severity and
interference (pain influence on function) subscale score of
the BPI significantly decrease for both groups at 3 months.
The pain severity index reduced at 3 months by 69 % for
StratticeTM patients by 73 % for Ultrapro patients. Simi-
larly, the functional interference index reduced at 3 months
by 66 % for StratticeTM patients and 76 % for Ultrapro
patients. There was no significant difference in the
C-reactive protein levels between the Strattice and Ultrapro
groups (0.55 ± 0.71 vs. 0.48 ± 0.5 mg/dl, respectively).
As shown in Table 7, there was no difference in surgeon or
patient satisfaction with the repair. Surgeons and patients
reported comparable levels of satisfaction with repairs
p value
affected with either mesh.
Analysis of the results of the patients categorized
0.50 according to whether they had their ilioinguinal nerve
0.57 divided intra-operatively showed that patients who had
their nerve divided had a greater reduction in pain from
their pre-surgery level compared to patients that did not
(3-month postoperative BPI severity scores minus preop-
erative scores: -6.4 ± 10.7 vs. -4.9 ± 7.3, p = 0.38,
respectively). This same pattern did not persist for the BPI
functional interference scores from the pre-surgery level,
with essentially no difference between patients with and
without the nerve division (-11.6 ± 25.9 nerve cut vs.
-10.5 ± 20.0 no division, p = 0.97). To investigate the
effect of the nerve being cut on the pain severity relative to
randomized treatment assignment, nerve division (yes/no)
was added to the analysis of variance model comparing the
pain severity between the two treatments. The results
suggest that there is no significant difference at 3-month
post-surgery between the two randomized treatment groups

123
228
in the change in pain severity (p = 0.910), after controlling
for the nerve being divided. Based on the pain dairy
maintained by the patients during the 10 days immediately
following the surgery, the pain scores were examined
within the 2 populations where the nerve was cut or
remained intact. In the 83 % of the patients where the
nerve was not cut, patients randomized to receive Ultrapro
reported an average of 14 % more pain on postoperative
day 1 (p = 0.028) and 13 % on postoperative day 3
(p = 0.045) compared to StratticeTM. The results were not
dissimilar in the patients whose nerve was cut during the
surgery. Patients randomized to receive Ultrapro with the
nerve cut reported an average of 7 % more pain on post-
operative day 1 and 20 % on postoperative day 3 compared
to StratticeTM; neither differences approached significance
due to the small number of patients in the analysis. In
summary, the results relative to postoperative pain on days
1 and 3 are not affected by the cutting of the nerve. Cer-
tainly, with only 17 % of the population to model with the
nerve cut does not provide a platform for deriving
significance.
Moreover, we analyzed the pain trajectory results for
patients stratified by anesthesia. Patients randomized to
receive StratticeTM and given general anesthesia had con-
sistently less pain over the 10 days following surgery,
based on the self-reported data recorded in the diary.
Although the mean pain scores were lower with StratticeTM
compared to Ultrapro, the differences were not statistically
different. No significant separation was seen between
patients randomized to StratticeTM compared to Ultrapro in
the patients who did not receive general anesthesia.
Additionally, the local anesthesia should not have long-
term effects on pain.
Discussion
Over the last two decades, the primary tissue repairs for
inguinal defects have given way to prosthetic mesh repairs.
The routine use of synthetic prosthetic material when
performing an inguinal herniorrhaphy has resulted in a
marked reduction in hernia recurrence rate. The rate is so
low that research efforts to reduce it further are not sta-
tistically relevant. Thus, efforts to improve inguinal her-
niorrhaphy have shifted to other considerations such as the
complication rate. Sequelae of inguinal hernia repair such
as chronic groin pain, convalescence, and effect on overall
quality of life are now being investigated in order to further
improve patient satisfaction with treatment of their inguinal
hernias. With over 750,000 inguinal herniorrhaphies per-
formed annually in the United States, at a cost estimated to
be several billion dollars [12], even a modest improvement
in these measures would have significant socioeconomic
123
Hernia (2014) 18:221–230
impact. It is for this reason that we felt that a study com-
paring one of the newer biologic prosthetics to a synthetic
mesh in tension-free repair was reasonable despite the
increased expense of the biologic. If a biological prosthesis
resulted in improved quality of life and decreased acute and
chronic pain, it might be worth the cost difference and
greater length of operative time.
Biologic prostheses differ from synthetic prostheses.
They are made from human and animal tissues, processed
physically, chemically, and enzymatically to remove cel-
lular material and antigens [6]. The resultant prostheses are
sheets of collagen fibers with various amounts of elastin
and other extracellular matrix proteins. The tissue response
to non-crosslinked biologic prostheses is generally one of
product degradation allowing host vessel/cell ingrowth
over several months. Biologic products have been used
successfully in complex abdominal wall surgery since
1994. The favorable experience with biologic meshes in the
ventral position has given reason to believe that they might
also serve well in the inguinal position, perhaps resulting in
less chronic inflammation, fibrosis, and chronic pain than
synthetic polymer meshes.
Three previous randomized clinical trials in Europe have
evaluated the use of biologic mesh versus heavy weight
synthetic mesh for elective inguinal hernia repair: one trial
used a heavily cross-linked porcine dermis material (Per-
macol; Coviden, Mansfield, MA) and the other two trials
used a porcine small intestinal submucosal material (Sur-
gisis; Cook, Bloomington, IA, USA) [13–15]. Each of
these trials chose as their primary endpoint post-surgical
pain assessed with a visual analog scale and/or a simple
verbal scale, and all reported a lower degree of pain in the
biologic group compared to the synthetic group. However,
all three of these prospective studies used heavy weight
polypropylene mesh in their control groups. Therefore, the
results from these studies might be skewed to favor bio-
logic mesh as there are two meta-analyses reporting that
lightweight meshes result in better patient outcomes after
inguinal herniorrhaphy compared to heavy weight mesh
[16–18]. In our study, we identified strategies to minimize
any design biases, and we chose a lightweight mesh in the
control arm. In fact, this study is the first blinded ran-
domized controlled trial in the United States reporting the
safety and the efficacy of Lichtenstein hernioplasty with
StratticeTM compared to a lightweight synthetic mesh. It
was conducted after the development of a detailed study
protocol with sufficient statistical power in nine high vol-
ume hernia centers. These centers were composed of aca-
demic medical centers, Veterans Affairs medical centers,
community hospitals, and ambulatory surgery centers.
Moreover, unlike the previous trials, we chose as the pri-
mary endpoint the patients’ functional status measured
with the hernia-specific Activities Assessment Scale
Hernia (2014) 18:221–230
(AAS). This is a relevant clinical outcome as its focus is on
measuring the quality of life after hernia repair, and it
allows comparison with other trials. Consistent with other
investigators, we observed a significant improvement in the
AAS after hernia repair in both groups. However, the mean
change in scores for the overall AAS between baseline and
3-month follow-up showed no difference between Strat-
ticeTM and Ultrapro mesh groups. By comparison, the
Permacol study [15], using generic measures of health-
related quality of life (SF-36, EuroQol), also showed no
difference between the synthetic and biologic groups at all
time points.
One of the secondary goals of this study was to deter-
mine whether StratticeTM could provide a secure repair
with a low recurrence rate. Toward this goal, we observed
no hernia recurrences at 3 months postoperatively.
Regarding safety and side effects, patients who underwent
StratticeTM hernioplasty showed no difference in the
postoperative complications (seroma, hematoma, infection)
compared to Ultrapro patients. However, an increasing
number of clinicians and researchers now consider post-
operative pain as one of the most important adverse effects.
In this study, we measured pain using several different
systems including the Brief Pain Inventory (BPI), a pain
visual analog scale (VAS), and a pain medication diary.
Patients in the StratticeTM group reported significantly less
pain during the first 3 days post-operatively (day 1–3)
compared to the Ultrapro patients, a difference which
dissipated over the remaining days. This finding might
suggest less acute inflammatory foreign body reaction.
However, at 3 months, both groups had less pain than at
baseline, but there is no difference in any of the pain
parameters between the StratticeTM and the Ultrapro arms.
Thus, at 3 months, we are not seeing an advantage of the
biological over the synthetic mesh in terms of chronic pain.
However, given the fact that synthetic mesh heals by
forming a scar plate, wound contraction and chronic
reaction/inflammation will continue over the long term.
Therefore, it is possible that differences between groups
may emerge with longer follow-up.
The present investigation has certain limitations. To come
to meaningful conclusions regarding hernia recurrence rates,
follow-up will need to be longer. All patients in this trial are
being followed for 2 years. Also, some might consider the
fact that the trial was sponsored by industry to be a limitation
but in reality the involvement of industry in clinical trials is
growing as few academic medical centers have the appro-
priate funding to conduct meaningful trials alone. Although
such shared roles between industry and academia may
potentially result in disagreements, we have learned that
appropriate planning and coordination of efforts will provide
added benefit to the quality of the study and insure that the
results obtained will most appropriately address the initial
229
hypotheses and goals for the effort. Such academic-industry
partnerships can provide the ability to explore new therapies
for diseases that might not otherwise be appropriately
investigated by either side alone. By using the clinical
coordinating centers from academic medical centers, cou-
pled with independent data monitoring funded by industry,
the ability to conduct a high-quality clinical trial is improved.
Conclusion
There are indications in the literature that the type of
prosthesis used in inguinal hernia repair may influence both
the patients’ quality of life and the incidence, severity, and
type of post-herniorrhaphy pain. A biologic prosthesis that
remodels into host tissue might therefore influence these
outcomes. However, by 3 months, the only significant
difference between patients repaired with a biologic pros-
thesis (StratticeTM) and a lightweight polypropylene mesh
(Ultrapro) was pain in the early postoperative course (day
1–3) in favor of StratticeTM. Otherwise, StratticeTM appears
to be comparable in both safety and efficacy in the short
term to a lightweight synthetic mesh. This certainly pro-
vides justification to continue the longer-term analysis to
see whether the theoretical advantages related to tissue
remolding with a biological prosthesis will be seen. The
protocol calls for data analysis at 12 and 24 months.
Conflict of interest All authors declare having received grant
support in relation to this study from LifeCell Corporation.
References
1. McCormack K, Scott NW, Go PM, Ross S, Grant AM, EU Hernia
Trialists Collaboration (2003) Laparoscopic techniques versus
open techniques for inguinal hernia repair. Cochrane Database
Syst Rev 1:CD001785
2. International Association for the Study of Pain (1986) Classifi-
cation of chronic pain. Descriptions of chronic pain syndromes
and definitions of pain terms. Prepared by the International
Association for the Study of Pain, Subcommittee on Taxonomy.
Pain Suppl 3:S1–S226
3. Nienhuijs S, Staal E, Strobbe L, Rosman C, Groenewould H,
Bleichrodt R (2007) Chronic pain after mesh repair of inguinal
hernia: a systematic review. Am J Surg 194:394–400
4. Di Vita G, Patti R, Barrera T, Arcoleo F, Ferlazzo V, Cillari E
(2010) Impact of heavy polypropylene mesh and composite light
polypropylene and polyglactin 910 on the inflammatory response.
Surg Innov 17:229–235
5. Klinge U, Klosterhalfen B, Birkenhauer V, Junge K, Conze J,
Schumpelick V (2002) Impact of polymer pore size on the
interface scar formation in a rat model. J Surg Res 103:208–214
6. Cornwell KG, Landsman A, James KS (2009) Extracellular
matrix biomaterials for soft tissue repair. Clin Podiatr Med Surg
26:507–523
7. Bellows CF, Shadduck PP, Helton WS, Fitzgibbons RJ (2011)
The design of an industry-sponsored randomized controlled trial
123
230
to compare synthetic mesh versus biologic mesh for inguinal
hernia repair. Hernia 15:325–332
8. Bellows CF, Alder A, Helton WS (2006) Abdominal wall
reconstruction using biological tissue grafts: present status and
future opportunities. Expert Rev Med Devices 3:657–675
9. Holzheimer RG (2004) First results of Lichtenstein hernia repair
with Ultrapro-mesh as cost saving procedure–quality control
combined with a modified quality of life questionnaire (SF-36) in a
series of ambulatory operated patients. Eur J Med Res 9:323–327
10. McCarthy M Jr, Jonasson O, Chang CH, Pickard AS, Giobbie-
Hurder A, Gibbs J, Edelman P, Fitzgibbons R, Neumayer L
(2005) Assessment of patient functional status after surgery. J Am
Coll Surg 201:171–178
11. Cleeland CS (2009) The brief pain inventory user guide. The
University of Texas MD Anderson Cancer Center, Houston, TX
12. Rutkow IM (1998) Epidemiologic, economic, and sociologic
aspects of hernia surgery in the United States in the 1990s. Surg
Clin North Am 78:941–951
13. Ansaloni L, Catena F, Coccolini F, Gazzotti F, D’Alessandro L,
Pinna AD (2009) Inguinal hernia repair with porcine small
intestine submucosa: 3-year follow-up results of a randomized
123
Hernia (2014) 18:221–230
controlled trial of Lichtenstein’s repair with polypropylene mesh
versus Surgisis Inguinal Hernia Matrix. Am J Surg 198:303–312
14. Puccio F, Solazzo M, Marciano P (2005) Comparison of three
different mesh materials in tension-free inguinal hernia repair:
prolene versus Vypro versus surgisis. Int Surg 90(3 Suppl):
S21–S23
15. Ridgway DM, Mahmond F, Moore L, Stojkovic S, Al-Mukhtar
A, Moore PJ (2005) A prospective double blinded randomised
control trial comparing porcine dermal collagen with polypro-
pylene mesh for inguinal hernia repair. Br J Surg 92:21
16. Markar SR, Karthikesalingam A, Alam F, Tang TY, Walsh SR,
Sadat U (2010) Partially or completely absorbable versus non-
absorbable mesh repair for inguinal hernia: a systematic review
and meta-analysis. Surg Laparosc Endosc Percutan Tech 20:
213–219
17. Gao M, Han J, Tian J, Yang K (2010) Vypro II mesh for inguinal
hernia repair: a meta analysis of randomized controlled trials.
Ann Surg 251:838–842
18. Sajid MS, Leaver C, Baig MK, Sains P (2012) Systematic review
and meta-analysis of the use of lightweight versus heavyweight
mesh in open inguinal hernia repair. Br J Surg 99:29–37