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Value Analysis Brief
Evidence for SYNTHECEL
Dura Repair
®
Introduction
This value analysis brief presents evidence for SYNTHECEL®
Dura Repair in the repair of dura mater (duraplasty) during
cranial surgery, following traumatic, neoplastic, or
inflammatory destruction. Materials used for dura
replacement include human tissues, animal tissues,
polymers, and biosynthetics. The ideal material should
alternatives to autologous transplantation and various
xenografts have been studied, however these xenografts
may be associated with adverse effects such as graft
dissolution, encapsulation, foreign body reaction, scarring,
and adhesion formation.3,4,5
prevent CSF leakage, be biocompatible, be free of potential
risk of infection, have excellent intra-operative handling,
and be readily available.1 An ideal dura substitute should also
have no harmful foreign body reaction, have mechanical
properties similar to human dura, and be storable.2
SYNTHECEL Dura Repair is an implant based on biosynthesized
cellulose technology. Biosynthesized cellulose technology
has been used as a wound dressing.6 The organism
Gluconacetobacter xylinus (formally Acetobacter xylinum)
is propagated in a nutritive culture media and forms a
cellulose pellicle of a specified weight and cellulose content
(g cellulose /cm2).7 SYNTHECEL Dura Repair has a unique
construction of non-woven, interconnected cellulose fibers,
which creates its strength. It functions as a mechanical layer
to protect and repair the dural defect while preventing
further cerebrospinal fluid (CSF) leakage. SYNTHECEL Dura
Repair is immunologically inert and has demonstrated minimal
foreign body response. It is a non-resorbable dural graft
with no adhesion formations, as demostrated in a clinical
trial, and is magnetic resonance (MR) safe. SYNTHECEL Dura
Repair is packaged wet and ready to use as one product for
either onlay or suture application.
The search for the most suitable dura mater substitute
continues because of the various disadvantages of the many
materials used to date. Native autologous tissue grafts can
perform well because they do not provoke severe
inflammatory or immunological reactions, but potential
drawbacks such as difficulty in achieving a watertight
closure, formation of scar tissue, insufficiently accessible
graft materials to close large dural defects, and additional
incisions for harvesting the graft remain problematic.3
Off-the-shelf dural substitutes have been developed as
Methods
We conducted a systematic review of peer-reviewed published literature using EMBASE, Medline, Google Scholar,
PubMed and Scopus databases. Clinical and laboratory
studies evaluating outcomes associated with the use of
SYNTHECEL Dura Repair were evaluated. The search terms
used were SYNTHECEL ‘biosynthesized cellulose‘,
‘acellular graft‘ and ‘(Synthes or Xylos) and dura‘, and
the search was limited to articles published in the past
10 years. Reference lists of selected studies were also
reviewed for possible additional articles.
value analysis Brief: Evidence for SYNTHECEL Dura Repair
Executive Summary
aggregated results across studies showed no adhesions, no risk of disease transmission, superior device strength, and
superior seal quality with SYNTHECEL Dura Repair (Table 1).8,9 SYNTHECEL Dura Repair thickness is similar to human
dura and conforms to the brain.8,23,24
Table 1: Summary of Results for SYNTHECEL Dura Repair
SYNTHECEL Dura Repair Clinical Evidence
Biosynthesized cellulose
• unique construction of non-woven, interconnected cellulose fibers, which creates its strength8
• functions as a mechanical layer to protect and repair dural defect while preventing further
CSf leakage8
• Demonstrated minimal foreign body response and immunologically inert9
No adhesions
No adhesion formations were observed in the 6-month randomized clinical study9
No Risk of Disease Transmission
Non-animal derived, no risk of transmissible diseases8
Sutureability
SYNTHECEL Dura Repair ranked as excellent in sutureability in 30% of cases vs 5.1% of cases in
the control group9
Strength of Device
SYNTHECEL Dura Repair exhibited superior device strength compared to control (p<0.0001)9
Seal Quality
SYNTHECEL Dura Repair exhibited superior seal quality compared to control (p=0.032)9
unmet Need in Dura Repair
Autografts
autologous human connective tissue (pericranium, fascia
lata) is material taken from the same individual and
remains the benchmark material to repair defects in the
dura mater. autologous tissue does not induce an
immunologic or severe inflammatory response and there
is no risk of transmissible diseases.10 Surgeons sometimes
avoid using autograft because there are instances where
there is not enough local replacement material of
sufficient quality to fill the dural defect, and therefore
they may have to take material from another area of the
body (most commonly the fascia lata), requiring a second
surgical site.10,11,12 This increases morbidity to the patient.
2
Allografts, Xenografts, and Synthetic Materials
allograft dural tissue from human cadavers is not often
used by surgeons and more recently has been associated
with the transmission of viral infections, including
Creutzfeldt-Jakob disease (CJD).13,14,15 Xenografts and
synthetics are the two most commonly used dural graft
materials, however, both materials present concerns for
patients and surgeons. Synthetics have been associated
with deep wound infections.16 Xenografts have been
associated with the transmission of viral infections and
have shown risk of hydrodynamic complications. This
includes persistent CSf leakage, development of
pseudomeningocele, noninfectious or aseptic meningitis,
and delayed hydrocephalus.17
value analysis Brief: Evidence for SYNTHECEL Dura Repair
a timeline of the evolution of technological advancement, research, and practice patterns in dura replacement is
presented in figure 1.2,14,15,16,18,19,20
Figure 1: Timeline of the Technological advancement, Research, and practice pattern Evolution in Dura Replacement
PRECLUDE synthetic polymer
from WL Gore received FDA
approval
Epidemic of bovine spongiform
encephalopathy in cattle and
emergence of a new variant
of Creutzfeldt-Jakob disease15
Human cadaveric dural tissue associated
with transmission of viral infections,
including Creutzfeldt-Jakob disease,
placed under special controls by the
FDA14,16,19
Rubber Tissue
Implantation by Abbe18
Freeze-dried Vacuum-Stored
Human Dural Tissue by Campbell18
1895
1958
Found that polymers may become
chronically colonized, microorganisms,
necessitating removal to eradicate
promoting continued growth of infection2
1996
Adhesion Formation
adhesion formation between dura mater and cortex and
the overlying temporalis muscle and galea following
decompressive craniectomy, can make subsequent
cranioplasty difficult and adds to the risks of the procedure.21
Animal tissues are the
most widely-used
materials
Launch of
SYNTHECEL
Dura Repair –
Biosynthesized
Cellulose Dural
Replacement
2014
adhesions between graft and cortex may also be clinically
significant because they might act as an epileptic focus.4
Thus, graft material to be used for dural repair should
either not produce cortical adhesions or form minimal ones.
Results
Clinical Studies of SYNTHECEL Dura Repair
Rosen et al. (2011)9 conducted a 6-month prospective
randomized controlled trial (RCT) to establish that
SYNTHECEL Dura Repair was not inferior compared with
other commercially-available dural replacement products
(made of bovine collagen (97.3%) and synthetic material
(2.7%) (N=99).
(p ≥ 0.3685), or radiologic endpoints (absence of
pseudomeningocele and CSf fistula) (p ≥ 0.4061).9
a statistically significant difference in favor of patients
implanted with SYNTHECEL Dura Repair over control was
observed for both device strength (p<0.0001) and device
seal quality (p =0.032).9
Overall Effectiveness
The primary hypothesis, non-inferiority of SYNTHECEL Dura
Repair was confirmed (p = 0.0206).9 No significant
difference was revealed between groups for surgical site
infection (p = 1.0000), wound healing assessment
Handling Qualities
Superior handling qualities were evident with SYNTHECEL
Dura Repair in the RCT.8 Ease of use was similar among
products; however device strength, sutureability, and seal
quality favored SYNTHECEL Dura Repair.9
3
Value Analysis Brief: Evidence for SYNTHECEL Dura Repair
Figures 2-5 illustrate the surgeon’s assessment of device handling characteristics across the patients treated
(n=62 SYNTHECEL Dura Repair, n=37 for control; the number of implants was used as the denominator to compute
all percentages and patients may have had more than 1 implant).9
Figure 2: Ease of Use was Similar Among Products
Figure 3: SYNTHECEL Dura Repair Exhibited Superior
Device Strength Compared to Control
60.0%
100.0%
97.4%
80%
60%
■ No
40%
■ Yes
20%
0%
Surgeon Response
52.2%
■ Excellent
■ Good
30.0%
■ Fair
0.0%
12.8%
10.3%
5.1%
5.1%
■ Poor
■ N/A
■ Good
17.9%
20.0%
10.0%
■ Fair
0.0% 3.3%
2.6%
P<0.0001
■ Poor
Control
(n=39)
Figure 5: SYNTHECEL Dura Repair Exhibited Superior
Seal Quality Compared to Control
40.0%
56.4%
53.3%
50.0%
34.3%
■ Excellent
30.0%
25.6%
20.0%
10.0%
0%
Control
(n=39)
■ Excellent
30.8%
30.0%
60.0%
12.8%
5.0%
48.7%
SYNTHECEL Dura Repair
(n=75)
66.7%
SYNTHECEL Dura Repair
(n=75)
4 51.7%
45.0%
40.0%
Control
(n=39)
Figure 4: SYNTHECEL Dura Repair Ranked Excellent
in 30% of Cases vs. 5.1% in the Control Group in
Sutureability
10.0%
0%
50.0%
0%
2.6%
0.0%
SYNTHECEL Dura Repair
(n=75)
80.0%
70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
Surgeon Response
100%
Surgeon Response
Surgeon Response
120%
■ Fair
12.8%
11.1%
0.0%
■ Good
5.1%
1.1%
SYNTHECEL Dura Repair
(n=75)
P=0.032
Control
(n=39)
■ Poor
Value Analysis Brief: Evidence for SYNTHECEL Dura Repair
Laboratory Studies of SYNTHECEL Dura Repair
An in vivo laboratory study of 36 New Zealand rabbits
evaluated the local response and the efficacy of
SYNTHECEL as compared to commercially available dural
membranes DuraGen® (Integra LifeSciences Corporation)
and Dura-Guard® Dural Repair Patch(Synovis Surgical
Innovations).8 Gross evaluation and histopathologic
evaluation in the rabbit craniotomy model at the implant
sites at 2, 4, and 13 weeks post implantation demonstrated
that SYNTHECEL was equivalent to DuraGen and
Dura-Guard Dural Repair Patch when used to replace the
dural membrane. The local inflammation response to
SYNTHECEL two weeks after implantation was similar to
that of DuraGen and less than that of Dura-Guard Dural
Repair Patch (Figure 6).
Figure 6: Local inflammatory response to SYNTHECEL Dura Repair, DuraGen, and Dura-Guard Dural Repair two weeks
after implantation8
SYNTHECEL
Conformable
SYNTHECEL Dura Repair is similar in thickness to human dura and conforms to the brain (SYNTHECEL Dura Repair is
0.26 mm and human dura is 0.35-0.58 mm.8,23,24
Hospital Inventory Management
Handling, moving, and processing of materials constitute about 35% to 40% of total supply chain costs in
hospitals.25,26 Improving medical and medical supply inventory management provides a great opportunity to improve
hospital savings.25,26 SYNTHECEL Dura Repair is one product choice for excellent onlay or suture performance.
Discussion
Based on these results, use of SYNTHECEL Dura Repair is expected to result in no adhesions, no risk of disease
transmission, superior device strength, and superior seal quality.
5
Value Analysis Brief: Evidence for SYNTHECEL Dura Repair
More About SYNTHECEL Dura Repair
SYNTHECEL Dura Repair is an assured and versatile solution for dura reconstruction needs:
• Clinically proven
• One product choice for excellent onlay or suture performance
• Superior handling
• No adhesions*
• Non-animal derived, no risk of transmissible diseases
• Non-progenic
• MR Safe
*Observed in clinical study.
References
1 Narotam P, Reddy K, Fewer D, Qiao F, Nathoo N. Collagen matrix duraplasty for cranial and spinal surgery: a clinical and imaging study. J Neurosurg. 2007;106:45-51.
2Yamada K, Miyamoto S, Nagata I, Kikuchi H, Ikada Y, Iwata H, Yamamoto K. Development of a dural substitute from synthetic bioabsorbable polymers. J Neurosurg.
1997;86:1012–7.
3Yu F, Wu F, Zhou R, Guo L, Zhang J, Tao D. Current developments in dural repair: a focused review on new methods and materials. Front Biosci (Landmark Ed).
2013;18:1335-43.
4Neulen A, Gutenberg A, Takács I, Wéber G, Wegmann J, Schulz-Schaeffer W, Giese A. Evaluation of efficacy and biocompatibility of a novel semisynthetic collagen
matrix as a dural onlay graft in a large animal model. Acta Neurochir (Wien). 2011;153(11):2241-50.
5 Barbolt TA, Odin M, Léger M, Kangas L, Hoiste J, Liu SH. Biocompatibility evaluation of dura mater substitutes in an animal model. Neurol Res. 2001;23(8):813-20.
6 Gerit D. Mulder, DPM, MS, Joseph P. Cavorsi, MD, Daniel K. Lee, DPM Wounds. 2007;19(7):173-182.
7 Williams WS, Cannon RE. Alternative environmental roles for cellulose produced by Acetobacter xylinum. Appl Environ Microbiol. 1989;55(10):2448-52.
8 Mechanical test data on file at DePuy Synthes. Mechanical test results are not necessarily indicative of clinical performance.
9Rosen CL, Steinberg GK, DeMonte F, Delashaw JB Jr, Lewis SB, Shaffrey ME, Aziz K, Hantel J, Marciano FF. Results of the prospective, randomized, multicenter clinical
trial evaluating a biosynthesized cellulose graft for repair of dural defects. Neurosurgery. 2011;69(5):1093-1104.
10 Hoover DA and Mahmood A. Osificaton of autologous percranium used in duraplasty. Case report. J Neurosurg. 2001;95(2):350-352.
11 Laquerriere A, Yun J, Tiollier J, Hemet J, Tadie M. Experimental evaluation of bilayered human collagen as a dural substitute. J Neurosurg. 1993;78(3):487-491.
12Tachibana E, Saito K, Fukuta K, Yoshida J. Evaluation of the healing process after dural reconstruction achieved using a free fascial graft. J Neurosurg.
2002;96(2):280-286.
13 Martínez-Lage JF, Sola J, Poza M, Esteban JA. Pediatric Creutzfeldt-Jakob disease: probable transmission by a dural graft. Childs Nerv Syst. 1993;9(4):239-42.
14von Wild KR. Examination of the safety and efficacy of an absorbable dura mater substitute (Dura Patch) in normal applications in neurosurgery. Surg Neurol.
1999;52(4):418-424; discussion 425.
15Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, Alperovitch A, Poser S, Pocchiari M, Hofman A, Smith PG. A new variant of Creutzfeldt-Jakob disease in the
UK. Lancet 1996; 347(9006):921-925.
16Malliti M, Page P, Gury C, Chomette E, Nataf F, Roux FX. Comparison of deep wound infection rates using a synthetic dural substitute (Neuro-Patch) or pericranium
graft for dural closure: a clinical review of 1 year. Neurosurgery. 2004; 54(3):599-603; discussion 603-594.
17Moskowitz SI Liu J, Krishnaney A. Postoperative complications associated with dural substitutes in suboccipital craniotomies. Neurosurgery. 2009;64(3 suppl.):28-33;
discussion 33-24.
18National Institutes of Neurological Disorders and Stroke (NINDS). Creutzfeldt-Jakob Disease Fact Sheet. Available at: http://www.ninds.nih.gov/disorders/cjd/detail_cjd.
htm. Accessed March 2, 2014.
19Macfarlane MR, Symon L. Lyophilised dura mater: experimental implantation and extended clinical neurosurgical use. J Neurol Neurosurg Psychiatry.
1979;42(9):854-858.
20 Narotam PK, van Dellen JR, Bhoola KD. A clinicopathological study of collagen sponge as a dural graft in neurosurgery. J Neurosurg. 1995;82(3):406-412.
21 Bulters D, Belli A. Placement of silicone sheeting at decompressive craniectomy to prevent adhesions at cranioplasty. Br J Neurosurg. 2010;24(1):75-6.
22 Data on file. DePuy Synthes Test bench testing and charts from IDE.
23Otano SE, Sacks MS, Malinin TI: Mechanical behavior of human dura mater. Transcripts from the BED Bioengg Conf-ASME 29: 329-330, 1995.
24 Sacks MS, Jimenez Hamann MC, Otano-Lata SE, Malinin TI. Local mechanical anisotropy in human cranial dura mater allografts. J Biomech Eng 120:541-544, 1998.
25Darling M and Wise S. Not your father's supply chain. Following best practices to manage inventory can help you save big. Materials Management in Health Care.
2010; 19(4): 30–33.
26 Gebicki M, Mooney E, Chen S, Mazue L. Evaluation of hospital inventory policies. Health Care Manag Sci. 2013: 1-15.
6 Limited Warranty and Disclaimer: DePuy Synthes CMF products are sold with a limited warranty to the original purchaser against defects in
workmanship and materials. Any other express or implied warranties, including warranties of merchantability or fitness, are hereby disclaimed.
WARNING: In the USA, this product has labeling limitations. See package insert for complete information.
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Manufactured by (United States):
Synthes CMF
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Telephone: (610) 719-5000
To order: (800) 523-0322
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Synthes (Canada) Ltd.
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Telephone: (905) 567-0440
To order: (800) 668-1119
Fax: (905) 567-3185
www.depuysynthes.com
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DSUS/CMF /0614/0120 7/14