Development and Characterization of Novel Electrospun Meshes For Hernia Repair
Development and Characterization of Novel Electrospun Meshes For Hernia Repair
Development and Characterization of Novel Electrospun Meshes For Hernia Repair
discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/276291238
CITATION READS
1 96
4 authors, including:
Jed Johnson
Nanofiber Solutions, Inc.
43 PUBLICATIONS 616 CITATIONS
SEE PROFILE
Some of the authors of this publication are also working on these related projects:
All content following this page was uploaded by Jed Johnson on 15 May 2015.
Received: March 13, 2015; Accepted: April 30, 2015; Published: May 05, 2015
*Corresponding author: Jed Johnson, Nanofiber Solutions, 1275 Kinnear Road, Columbus, Ohio 43212, USA, Tel: +614-453-5877; Fax: +614-487-3704;
E-mail: [email protected]
organs [5].
Abstract
Biologic meshes are the most recent addition to the list of
The use of surgical mesh for hernia repair has become widespread,
as have the types of surgical mesh available on the commercial market.
materials available for use in hernia repair. They are typically
Biologic meshes are the most recent addition to the list of materials made of decellularized dermal matrix tissue derived from either
available for use in hernia repair, but the mechanical properties of human cadaveric or porcine sources [6]. These materials facilitate
these meshes are not always adequate for hernia repair applications. regenerative tissue formation and native collagen deposition
Electrospun polymer nanofibers have generated significant interest prior to resorption and are often used in contaminated wound
as a cell scaffolding material, but the literature characterizing sites. Their mechanical properties, however, are not ideal for
these meshes for hernia repair applications is limited. In this work,
surgical mesh applications and it can be hard to predict how
novel electrospun nanofiber meshes made of PCL, PDO, PLGA1090,
PLGA8218, PLLA, PU, and PET were successfully manufactured and quickly the mesh will resorb in vivo leading to revision surgeries.
characterized using standardized tests for hernia meshes from ISO Decellularized matrix materials also tend to undergo plastic
and ASTM, including ball burst strength, suture retention strength, deformation over time as a result of stress caused by intra-
trouser tear strength, radial stiffness, and ultimate tensile strength abdominal pressure, which can lead to bulging of the abdominal
in order to set a universal foundation that others can use in the wall and recurrent hernia. Biologic materials alone are therefore
future development of medical devices utilizing electrospun meshes. insufficient for bridging fascial defects [7].
Surprisingly, the bioresorbable polymers outperformed the non-
resorbable polymers in the mechanical tests. PCL, PLGA8218, and Electrospun polymer nanofibers have generated significant
PLLA meshes had sufficient mechanical properties for use in hernia interest as a cell scaffolding material. These fibers have diameters
repair applications, but the PLLA mesh emerged as a favorable in the sub-micron range and replicate the morphology of the
prospect for further development as a surgical mesh with an ultimate
extracellular matrix found throughout the body. The high surface
tensile strength of 35.85 ± 2.45 N/cm, a suture retention strength of
17.3 ± 4.3 N and a ball burst strength of 92.32 ± 25.38 N/cm. Future area to volume ratio of nanofiber mesh promotes cell adhesion
work to characterize the in vivo response of the PLLA mesh will be and proliferation, while the high porosity promotes nutrient
needed to facilitate the translation of this electrospun hernia mesh and gas exchange [8]. Nanofibers can be electrospun using
to the clinic. biocompatible polymers with a wide range of in vivo resorption
Keywords: Nanofibers; Hernia repair; Surgical mesh; periods and minimal inflammatory reactions. Furthermore,
Electrospinning; Tissue engineering through polymer selection and manipulation of electrospinning
parameters, it is possible to fine-tune the mechanical properties
of electrospun scaffolds [9,10]. Fibers can also be spun such that
Introduction they are predominately oriented in the same direction, which can
Synthetic polypropylene mesh was first used for hernia repair result in anisotropic mechanical properties and control of cell
in 1958 [1,2]. Surgical mesh was a significant improvement over orientation [11,12].
suture-based methods due to the ability of the mesh to close A typical electrospinning setup consists of a high voltage
defects and support the surrounding abdominal wall tissue [3]. power source connected to the tip of a syringe with a metal
As a result, the use of surgical mesh for hernia repair has since needle. The syringe is filled with a viscous polymer solution and
become extensive, as have the types of surgical mesh available on placed in a pump set to dispense the solution at a constant rate.
the commercial market. In addition to permanent polypropylene As the solution flows from the tip of the syringe, it is charged
and polyethylene meshes, there are a plethora of resorbable by the high voltage power source, which exerts electrostatic
meshes tailored to break down in vivo as the hernia site heals [4]. forces on the solution at the tip of the needle, and causes it to
Meshes are often paired with visceral-side barrier layers to form form a Taylor cone. A jet of solution ejects from the Taylor cone
composite materials that reduce the risk of adhesion to internal and destabilizes in mid-air. As the solvent evaporates, solid
Citation: Chakroff J, Kayuha D, Henderson M, Johnson J (2015) Development and Characterization of Novel Electrospun Meshes for Page 2 of 9
Hernia Repair. SOJ Mater Sci Eng 2(2): 1-9.
Development and Characterization of Novel Electrospun Meshes for Hernia Repair Copyright:
© 2015 Johnson
sample was averaged and recorded in Newtons (N) assuming a 1 Excel for a right tailed t-distribution with α = 0.05.
mm thick sheet.
Results
Suture retention strength
The mesh characterization data is summarized in Table II.
Five 1 × 2 cm sheets of each mesh composition was cut. A 2-0
Scanning electron microscopy
nylon suture was passed through the mesh 2 mm from the 1 cm-
long edge of each sample and tied to form a loop. The knotted Low (100 μm scale bar) and high (10 μm scale bar)
end of the suture was secured in the upper clamp and the mesh magnification SEM images of each composition are shown in
test sample was secured in the bottom clamp. The suture was Figures 1 and Figure 2. Fiber diameter data is summarized in
then pulled until it tore through the sample following ISO 7198. Table II. All meshes were composed of solid, uniform fibers. No
The peak load from each sample was averaged and recorded in signs of beads were observed, nor were there any indications
Newtons (N) assuming a 1 mm thick sheet. that the fibers were wet or bonded to one another. The average
fiber diameters of each material were PLGA1090: 3.28 ± 0.57 μm,
Uniaxial tensile testing PET: 2.47 ± 0.69 μm, PLLA: 1.48 ± 0.67 μm, PLGA8218: 1.28 ±
Five tensile dogbones were cut from sheets of each mesh 0.38 μm, PU: 0.89 ± 0.33 μm, PDO: 0.86 ± 0.42 μm, and PCL: 0.64
composition according to ASTM D638 Type V. The ends of each ± 0.32 μm.
dogbone sample were clamped to opposite arms of the testing Density measurements
machine and pulled apart until failure. The peak load from each
sample was averaged and recorded in Newtons per centimeter Mesh density values are displayed in Figure 3 and Table II.
(N/cm) assuming a 1 mm thick sheet. The elongation to failure PCL had the lowest mesh density of 157 GSM, while PLGA8218
of each sample was also recorded. Elastic modulus of each had the highest mesh density of 285 GSM. The rest of the mesh
sample was determined from the slope of the linear regime of the densities were PDO: 210 GSM, PLGA1090: 263 GSM, PLLA: 222
resulting stress-strain curve. The average elastic modulus of each GSM, PU: 256 GSM, PET: 194 GSM.
sample was recorded in MPa. Ball burst strength
Statistics BBS values are presented in Figure 4 and Table II. PET mesh
Single sample t-tests were performed comparing the average had a BBS of 29.2 N/cm, the lowest of all the mesh compositions
test results of every material to generally accepted threshold evaluated. The strongest materials tested were the PLLA and PU
values in the published literature. The threshold values were BBS: meshes, which had BBS of 92.3 N/cm and 91.3 N/cm, respectively.
50 N/cm, SRS: 20 N, TTS: 20 N, UTS: 16 N/cm [1,4,14]. There is PET was the only mesh tested with a BBS significantly lower than
no generally accepted threshold value for radial stiffness. Single the 50 N/cm threshold. The BBS of PCL and PLGA8218 were
sample t-tests were also performed comparing the results of each not significantly different than the 50 N/cm threshold. PDO,
PLGA1090, PLLA, and PU all had BBS significantly higher than
material to published mechanical values of MotifMESHTM (Proxy
the 50 N/cm threshold. All meshes tested had significantly higher
Biomedical), an FDA-approved commercial surgical mesh. The
BBS than MotifMESHTM except PET, which had a significantly
test values of MotifMESHTM were BBS: 43.56 N/cm, SRS: 27.7 N,
lower BBS.
TTS: 15.1 N, RS: 2.8 N, UTS: 105.3 N/cm [15]. T critical values
were calculated using the following equation: Radial stiffness
x − µ0 Radial Stiffness values are portrayed in Figure 5 and Table
t=
s/ n II. PLGA1090 and PLGA8218 meshes had the highest RS values
In which t is the t-critical value, x is the sample mean, µ0 is of 5.0 N and 4.0 N, respectively. PCL and PDO meshes had the
the control value, s is the standard deviation of the sample group, lowest RS values of 0.53 N and 0.57 N, respectively. PCL, PDO, PU,
and n is the number of samples in the group. Degrees of Freedom and PET all had significantly lower RS than MotifMESHTM. The
were equal to n - 1. P values were calculated using Microsoft RS of PLGA8218 and PLLA were not significantly different from
Citation: Chakroff J, Kayuha D, Henderson M, Johnson J (2015) Development and Characterization of Novel Electrospun Meshes for Page 3 of 9
Hernia Repair. SOJ Mater Sci Eng 2(2): 1-9.
Development and Characterization of Novel Electrospun Meshes for Hernia Repair Copyright:
© 2015 Johnson
Figure 1: Panel of low magnification (left column, 100 µm scale bar) Figure 2: Panel of low magnification (left column, 100 µm scale bar)
and high magnification (right column, 10 µm scale bar) SEM images of and high magnification (right column, 10 µm scale bar) SEM images of
PCL (a,b), PDO (c,d), PLGA1090 (e,f), and PLGA8218 (g,h). PLLA (a,b), PU (c,d), and PET (e,f).
Citation: Chakroff J, Kayuha D, Henderson M, Johnson J (2015) Development and Characterization of Novel Electrospun Meshes for Page 4 of 9
Hernia Repair. SOJ Mater Sci Eng 2(2): 1-9.
Development and Characterization of Novel Electrospun Meshes for Hernia Repair Copyright:
© 2015 Johnson
Figure 3: Mesh density of electrospun polymer meshes. Error bars represent standard deviation.
Figure 4: Ball Burst Strength values of electrospun polymer meshes, MotifMESHTM, and published threshold value. Error bars represent standard
deviation when available.
* Material met or exceeded threshold value
a Material met or exceeded MotifMESHTM
were significantly lower than the 20 N threshold value. The value of 28.1 N. PDO had the lowest SRS of 10.1 N. The SRS of
TTS of PLGA8218, PLLA, and PU were not significantly different PDO, PET, and PLGA1090 were all significantly lower than the
from the 20 N threshold values. The TTS of PCL was significantly 20 N threshold values. The SRS of PCL, PLLA, and PU were not
higher than the 20 N threshold values. PDO, PLGA1090, and PET significantly different from the 20 N threshold values. PLGA8218
all had TTS values significantly lower than that of MotifMESHTM. was the only material with a SRS significantly higher than 20 N.
The TTS of PU was not significantly different than MotifMESHTM. PLGA8218 was also the only mesh tested that was not significantly
PCL, PLGA8218, and PLLA had TTS values higher than that of different than the MotifMESHTM control. All other meshes had a
MotifMESHTM. significantly lower SRS than MotifMESHTM.
Citation: Chakroff J, Kayuha D, Henderson M, Johnson J (2015) Development and Characterization of Novel Electrospun Meshes for Page 5 of 9
Hernia Repair. SOJ Mater Sci Eng 2(2): 1-9.
Development and Characterization of Novel Electrospun Meshes for Hernia Repair Copyright:
© 2015 Johnson
Figure 6: Trouser tear strength of electrospun polymer meshes, MotifMESHTM, and published threshold value. Error bars represent standard
deviation when available.
*Material met or exceeded threshold value
a Material met or exceeded MotifMESHTM
had the highest UTS of 189.6 N/cm, while the PCL mesh had the bioresorbable and non-resorbable polymers for hernia repair
lowest UTS of 20.1 N/cm. PU had the highest elongation to failure and act as a point of reference for the tissue engineering field
of 1,107% and PLGA8218 had the lowest elongation to failure at in the future development of electrospun scaffolds. The ideal
136%. PLGA8218 had the highest elastic modulus of 103.3 MPa hernia mesh should be lightweight and flexible to reduce pain
and PU had the lowest elastic modulus at 1.4 MPa. Every mesh and foreign body sensation, as well as maintaining sufficient
tested had UTS significantly higher than the 16 N/cm threshold strength and durability to bridge fascial defects with minimal
value except PCL, which was not significantly different than the risk of recurrent hernia [1]. Through careful design, electrospun
threshold value. Every mesh tested had significantly lower UTS nanofiber meshes can balance these contradictory mechanical
than MotifMESHTM except PU, which had significantly higher properties and provide a compromise between the mechanical
UTS. stability of macrofiber meshes and the biocompatibility of
Discussion biologically derived meshes.
This study was conducted in order to characterize the In order to be considered sufficient for use in hernia repair
mechanical properties of nanofiber meshes made of various applications, a mesh must have a minimum BBS of 50 N/cm, SRS
Citation: Chakroff J, Kayuha D, Henderson M, Johnson J (2015) Development and Characterization of Novel Electrospun Meshes for Page 6 of 9
Hernia Repair. SOJ Mater Sci Eng 2(2): 1-9.
Development and Characterization of Novel Electrospun Meshes for Hernia Repair Copyright:
© 2015 Johnson
Figure 7: Suture retention strength of electrospun polymers, MotifMESHTM, and published threshold value. Error bars represent standard deviation
when available.
* Material met or exceeded threshold value
a Material met or exceeded MotifMESHTM
Figure 8: Ultimate tensile strength of electrospun polymer meshes, MotifMESHTM, and published threshold value. Error bars represent standard
deviation when available
* Material met or exceeded threshold value
a Material met or exceeded MotifMESHTM
of 20 N, TTS of 20 N, and UTS of 16 N/cm [1,4,14]. Based on the PU mesh underwent large amounts of elastic deformation before
statistical analyses, every mesh tested met or surpassed the 50 it reached its peak load. This is demonstrated by the > 1,100%
N/cm BBS threshold except PET. PCL, PLGA8218, PLLA, and PU elongation of the PU mesh during UTS testing. If PU mesh was
met or surpassed the 20 N SRS threshold, as well as the 20 N TTS implanted over a hernia site, it would likely allow the wound to
threshold. All of the meshes tested met or surpassed the UTS reopen and may even herniate through the wound along with the
threshold value of 16 N/cm. PET, PDO, and PLGA1090 meshes viscera before reaching a sufficient strength to stop the hernia
did not meet one or more of the threshold values, and therefore site from opening any further.
are not suitable candidates for use in hernia repair applications. PCL, PLGA8218, and PLLA met or surpassed all of the
Although PU met or surpassed all of the threshold values, it is mechanical test threshold values. PCL had the highest TTS,
also not a viable candidate for hernia repair. During each test, the and was the only material of the three to surpass both the
Citation: Chakroff J, Kayuha D, Henderson M, Johnson J (2015) Development and Characterization of Novel Electrospun Meshes for Page 7 of 9
Hernia Repair. SOJ Mater Sci Eng 2(2): 1-9.
Development and Characterization of Novel Electrospun Meshes for Hernia Repair Copyright:
© 2015 Johnson
threshold value and the MotifMESHTM value. The BBS and UTS of type III collagen. This compromises the mechanical integrity
of PCL, however, were lower than those of PLLA and PLGA8218. of the patient’s connective tissue, and increases the likelihood of
PLGA8218 had the highest UTS of the three materials, and hernia formation and recurrence. In cases such as these, even if a
was the only material tested with a SRS comparable to that of resorbable mesh led to the complete regrowth and remodeling of
MotifMESHTM. The BBS of PLGA8218, however, was significantly healthy fascia, patients would still be prone to recurrences after
lower than that of PLLA, and the TTS of PLG8218 was the lowest the mesh was resorbed.
of the three. PLLA mesh had the highest BBS, as well as the second
highest TTS and UTS of the three. The only test in which PLLA A composite mesh made up of an electrospun PLLA layer
was outperformed by both PCL and PLGA8218 was SRS; however backed by a permanent mesh could be a solution to this issue. The
the SRS of PLLA was not significantly different than the 20 N SRS electrospun PLLA mesh would adhere to the abdominal wall and
threshold value. Furthermore, the SRS testing protocol tests the promote tissue growth across the defect during the initial stages
force necessary to pull out a single suture. Assuming multiple of wound healing. As the PLLA layer gradually degrades in the
sutures will be used to fix the mesh in place in vivo, the actual months following implantation, it would transfer the mechanical
SRS of the implanted mesh would be many times that of the test load onto the newly formed fascia and the permanent mesh
value. PLLA also performed well compared to MotifMESHTM. layer. The permanent mesh would remain and play a permanent,
Although MotifMESHTM outperformed PLLA in UTS and SRS supplemental role in order to prevent recurrences. Furthermore,
testing, PLLA surpassed MotifMESHTM in BBS as well as TTS. this permanent mesh layer could have large pores and a low
The RS of PLLA was also comparable to that of MotifMESHTM. mesh density to reduce chronic foreign body reaction. This mesh
Mesh stiffness is an important factor to consider because a mesh could be produced by electrospinning a nanofiber layer directly
that is too stiff may restrict the patient’s range of motion in the on to a polypropylene sheet coated with a thin layer of resorbable
abdominal region, causing discomfort, while a mesh that is too adhesive to prevent delamination.
flexible may be difficult for surgeons to handle during the hernia
repair procedure [1]. Although no universal radial stiffness One study suggests that composite materials result in an acute
standards or testing procedures have been established by the inflammatory response as the resorbable polymer degrades,
medical community at this time, the fact that the stiffness of PLLA usually into acidic byproducts, and offer no benefits over simple
is nearly equal to that of MotifMESHTM, a commercial surgical permanent meshes [16]. The composites tested in this study
mesh approved by the FDA, is encouraging. Therefore, we believe were composed of a permanent mesh fixed to a resorbable film,
the electrospun PLLA mesh is the most suitable material for use and films may not offer any significant benefits to counteract
in hernia repair applications. the negative impact of local inflammation in response to their
degradation. Furthermore, these films are often used as adhesion
PLLA also offers several advantages from an in vivo
barrier layers and have no direct interaction with the hernia
degradation standpoint. PCL, PDO, PLGA1090, PLGA8218, and
PLLA are all bioresorbable polymers, and therefore break down site [5]. Conversely, it has been demonstrated that resorbable
by natural processes in vivo. One advantage of resorbable meshes nanofiber layers in direct contact with the hernia site promote
is a reduction of the long term foreign body response that often collagen deposition and remodeling, and yield better mechanical
persists in patients with permanent mesh implants [16]. Due properties at the wound interface compared to polypropylene
to chemical and structural differences, all of these polymers mesh alone [21]. This suggests that if the adhesion barrier layer
degrade at different rates. PDO and PLGA1090, for example, are was made from nanofibers instead of a film, there would be a
completely resorbed in a matter of weeks post implantation. significantly lower inflammatory response.
This short degradation profile does not give the hernia site
Conclusions
adequate time to heal before the supporting mesh is gone, which
may result in a high rate of recurrence in the years following a Electrospun nanofiber scaffolds have the potential to provide
procedure [17]. PLLA, however, degrades over the course of 9-12 a cheap, reproducible hernia mesh with customized mechanical
months. In some circumstances, this may provide enough time properties, degradation rates and an excellent capacity to support
for native fascia to grow and remodel at the hernia site before native tissue regeneration, but to date there has been no published
the mechanical load is transferred from the mesh to the healed literature characterizing electrospun meshes for hernia repair. In
tissue. For example, a recent pilot study on the use of a resorbable this work, novel electrospun nanofiber meshes were successfully
mesh plug for inguinal hernia repair came to the conclusion that manufactured and characterized using standardized tests for
the plug was suitable for use in young and healthy patients with hernia meshes from ISO and ASTM in order to set a universal
minor hernias [18]. foundation those others can use in the future development of
While fully resorbable meshes may be useful in some medical devices. The data demonstrates that PCL, PLGA8218,
circumstances, they will likely never be suitable for general use and PLLA electrospun meshes met or exceeded the minimum
in hernia repairs. There is a growing body of evidence which mechanical requirements for use in hernia repair applications.
suggests a genetic predisposition to hernia formation and The mechanical properties of electrospun PLLA mesh make it
recurrence in some patients [19,20]. A large portion of patients an ideal candidate for further development. Future studies will
with recurrent hernias have a genomic profile displaying need to be performed to evaluate the in vivo response of these
decreased expression of type I collagen and increased expression electrospun nanofiber meshes prior to clinical translation.
Citation: Chakroff J, Kayuha D, Henderson M, Johnson J (2015) Development and Characterization of Novel Electrospun Meshes for Page 8 of 9
Hernia Repair. SOJ Mater Sci Eng 2(2): 1-9.
Development and Characterization of Novel Electrospun Meshes for Hernia Repair Copyright:
© 2015 Johnson
10. Johnson J, Niehaus A, Nichols S, Lee D, Koepsel J, Anderson D, et al. 20. Klinge U, Zheng H, Si Z, Schumpelick V, Bhardwaj RS, Muys L, et al.
Electrospun PCL in Vitro: a Microstructural Basis for Mechanical Expression of the extracellular matrix proteins collagen I, collagen III
Property Changes. J Biomater Sci Polym Ed. 2009; 20(4): 467-81. doi: and fibronectin and matrix metalloproteinase-1 and-13 in the skin of
10.1163/156856209X416485. patients with inguinal hernia. Eur Surg Res. 1999; 31(6): 480-90.
11. Johnson J, Nowicki MO, Lee CH, Chiocca EA, Viapiano MS, Lawler 21. Plencner M, East B, Tonar Z, Otáhal M, Prosecká E, Rampichová M,
SE, et al. Quantitative Analysis of Complex Glioma Cell Migration on et al. Abdominal closure reinforcement by using polypropylene
Electrospun Polycaprolactone Using Time-Lapse Microscopy. Tissue mesh functionalized with poly-epsilon-caprolactone nanofibers and
Eng Part C Methods. 2009 Dec;15(4):531-40. doi: 10.1089/ten. growth factors for prevention of incisional hernia formation. Int J
TEC.2008.0486. Nanomedicine. 2014; 9: 3263-77. doi: 10.2147/IJN.S63095.
12. Agudelo-Garcia PA, De Jesus JK, Williams SP, Nowicki MO, Chiocca EN,
Citation: Chakroff J, Kayuha D, Henderson M, Johnson J (2015) Development and Characterization of Novel Electrospun Meshes for Page 9 of 9
Hernia Repair. SOJ Mater Sci Eng 2(2): 1-9.