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High Strength Multi layered Biomesh For Hernia
Repair
LANCE MARX KEITH OSTROWSKI LU SONG IAN MACDOWALL
Executive Summary
Every year, over twenty million hernia repairs are performed worldwide. Nearly one third
of patients require secondary operations for hernia recurrence due to inferior mesh design.​1,8 ​Our
proposed biologic will decrease the infection and adhesion to organs compared to polymer
meshes and yield an improved strength profile compared to biologic meshes. The improved
strength and histological response will yield a lower recurrence rate and better post-surgical
outcomes. We request $300,000 to make a working prototype of this mesh and to pursue a patent.

Technical Need
Approximately 700,000 U.S. patients and over 20 million worldwide undergo ventral
hernia repair annually.​1 Of these patients, nearly of them require a secondary operation for
hernia recurrence due to mesh tearing.​ The current solutions for ventral hernias are using either
8

synthetic or biologic mesh in order to reinforce the weak abdominal wall. Synthetic meshes pose
a large risk for infection and inflammation of tissues neighboring the mesh, as well as the buildup
of blood pockets known as seromas. Biologics typically lack the strength profile to withstand
intraabdominal forces, as well as risk volatile allergic response within the host. We are creating a
new mesh that incorporates the strengths of both synthetic and biological components.
Most polymer meshes, such as the common polypropylene mesh, cost about $0.14 per
linear centimeter and about $5.00 per square centimeter​.2​ ​Although this mesh option is cheap in
comparison to biologics, these polypropylene meshes warrant the highest risk of complication
such as inflammation and infection. Modern biologic meshes, in comparison,

Technical Goals
The primary goal of this project is to develop a working prototype and patent a
multi-layered biologic hernia mesh design using a resorbable lockstitch polymer border and
removable chain stitched polymer sewn throughout to improve tensile strength, porosity, and
histological response. This will be done with three different steps:
1: Develop optimal methods for stitching polymer into biologic mesh to maximize strength and
porosity
2: Determine optimal number of biologic layers to maximize cost efficiency without sacrificing
strength
3: Perform in vivo trials to evaluate the long-term histological response
The completion of these goals will mark success and forge the path towards a paramount
mesh design. The first task is to optimize sewing methods, including machine customization and
polymer threading configuration, in order to create the maximum macroporous profile without
sacrificing a critical amount of strength. The second goal will be to perform strength testing to
ensure the mesh can withstand the forces of the abdominal wall. The final goal is to implant the
mesh into animal models in order to assess both possible adverse histological responses in
surrounding tissues and possible degradation of the bovine acellular dermal matrix (BADM) and
poly (lactic-co-glycolic-acid) (PLGA) threading.

Technical Approach
Task 1: Stitching Optimization of Machine and PLGA/PP

Full Proposal
Materials Selection Competition
High Strength Multi layered Biomesh For Hernia
Repair
LANCE MARX KEITH OSTROWSKI LU SONG IAN MACDOWALL
Sewing optimization will be done using the Brother BAS-311hn-305a sewing machine.
Customization will include properly programming the machine, configuring the proper stitch
pattern into the BADM, determining the ideal radii for PLGA and polypropylene (PP), and
determining the ideal stitch lengths for PLGA and polypropylene. Production of BADM will be
done first by purchasing bovine dermis from a local abattoir. Samples of bovine dermal matrix
will be decellularized using a common surfactant, sodium dodecyl sulfate.​3
The new mesh will be comprised mostly of multilayered BADM. This decellularized
biologic has a high tensile strength, decreased risk for allergic response, and increased propensity
for fibrous ingrowth of host tissue. The strength profile of BADM compares favorably to Porcine
Acellular Dermal Matrix, for example (Figure 1). Multiple layers of BADM will be held together
by a lockstitch bordering of poly (lactic-co-glycolic-acid), or PLGA. This biodegradable polymer
has a high tensile strength and has been used extensively in clinical applications. PLGA has a
customizable reabsorption time through the addition or omission of glycolic acid groups, meaning
that PLGA threads can be optimized based on the patient’s risk factors. The center of the
multilayered mesh will be chainstitched with a tagged polypropylene threading. This
chain-stitched network will maintain rigidity of the mesh during operation. Once the mesh is
implanted, the polypropylene threading can be easily removed by cutting the tag and unraveling.
This will create a network of pores that will reduce the risk of seroma formation and will further
the scaffolding ability for host tissue integration.

Figure 1. Strength Comparison of Bovine Acellular Dermal Matrix (BADM) and Porcine Acellular
Dermal Matrix (PADM)

Various radii of PLGA and PP will be used across differing mesh compositions. PLGA
will be configured in order to hold layers of BADM together. Various compositions of PLGA will
be tested in varying configuration, as the strength and resorption time of PLGA are related to the
amounts of poly (glycolic-acid) and poly (lactic-acid) respectively. Polypropylene, on the other
hand, will be configured to give the best macroporosity potential without sacrificing strength.
Radii between 0.5 mm and 1.5 mm will be tested in different meshes to create pores ranging from
1 mm to 3 mm, which will form ideal networks that will allow for fibrous ingrowth without the
buildup of scar tissue​.4​ ​Fluid flow of the mesh will be analyzed according to ASTM Standards for
capillary flow of geotextiles​.5​ ​The PLGA threading, in addition to radii and stitch length, shall be
customized in composition. A higher composition of poly (glycolic-acid) will hasten resorption
time, while a higher composition of poly (lactic-acid) will strengthen mechanical properties of the
thread​.6​

Full Proposal
Materials Selection Competition
High Strength Multi layered Biomesh For Hernia
Repair
LANCE MARX KEITH OSTROWSKI LU SONG IAN MACDOWALL

Figure 2. Final Mesh Design with chain stitched PP and lock stitched PLGA border

Task 2: Strength Optimization


The second stage will involve testing the biaxial tensile strength of various configurations
of our hernia mesh. Configurations will include mesh designs with varying polymer radii and
stitch length as well as varying number of layers of Bovine Acellular Dermal Matrix (BADM).
The chain-stitched polypropylene will be removed from the mesh configurations prior to testing
to accurately represent the in-vivo tensile strengths of the mesh.Testing of these designs will
utilize the Instron 3345 to determine the tensile strength profiles in the length and width directions
of the meshes.
Once tensile testing of the configurations of the mesh are completed, the biaxial tensile
strength values of the meshes will be compared to experimental values of the in-vivo forces in the
abdominal wall for patients of varying weights. These comparisons will allow us to determine the
ideal number of layers of BADM to use for patients based on their weight. After confirming that
the mesh configurations can withstand the forces of the abdominal wall, the tensile strength
values of the configurations will be compared with each other. This is to determine the strongest
and most cost-effective mesh configurations in terms of amount of material used.

Task 3: Evaluating Histological Response and Degradation of Mesh in Live Testing


The final stage will involve testing the strongest and most cost effective configurations of
mesh in 30 rabbit models. Incisions 3 cm in length will be made in rabbit abdominal walls in
different locations to induce ventral hernias. Meshes will be implanted using prolene sutures as an
adhering agent to abdominal tissue. Meshes will be removed from the models at 1 month, 3
month, and 6 month time marks. Intestinal and abdominal tissue neighboring the mesh will be
observed in order to assess any adverse reactions such as inflammation, infection, seroma
formation, host rejection of the mesh, and adhesion of the mesh to unfavorable neighboring
tissues.
Meshes will also be analyzed for any potential degradation and elongation due to abrasion
within the abdominal wall and abdominal forces. Ten rabbits will be used to assess each time
mark for histological responses and mesh degradation. The initial incision used to implant the
mesh will be reopened in each model, and the tissues surrounding the mesh will be analyzed for

Full Proposal
Materials Selection Competition
High Strength Multi layered Biomesh For Hernia
Repair
LANCE MARX KEITH OSTROWSKI LU SONG IAN MACDOWALL
inflammation, infection, and other negative responses. Once host tissue analysis is complete, the
mesh will then be removed from the models and the entire mesh (BADM and PLGA threading)
will be subjected to similar strength testing as in Task 2 in order to evaluate any degradation and
change in strength properties.
This last step is the most important in terms of success. These final tests are performed in
order to assess any risk to patients who use the mesh. If the BADM does not have a favorable
integration into the body, the host could reject the mesh and face a dangerous response. On the
other hand, the strength of the mesh could either increase or decrease with elongated time within
the body. If strength of the mesh increases with time, then the mesh successfully allows fibrous
ingrowth and enables the mesh to be entirely incorporated into the host. If mesh strength
decreases too rapidly as a function of time, then layers of the mesh could tear, decreasing the
overall integrity of the mesh. If the PLGA is degrading too quickly, whether by internal abrasion
and force or too hasty of a resorption time, then the thread could break and cause the entire mesh
to unravel.

Scientific, Economic, and Social Impact


From a scientific and social perspective, the new mesh design includes multilayered
Bovine Acellular Dermal Matrix (BADM), a bio-mesh, as a majority of the material, and the
synthetic polymers: polypropylene and poly (lactic-co-glycolic acid) (PLGA) for center threading
and for border threading, respectively. All the materials are commonly used mesh materials and
have extensive clinical experience. The properties and applications of the materials have been
studied over many years. ​These materials have been developed and transferred to the market as
medical materials for in vivo application. Examples include PROLENE​® ​(polypropylene hernia
mesh) by Ethicon US, LLC, ​Degradex​® (PLGA) by Phosphorex, Inc. The mature and stable
markets for BADM, PLGA, and polypropylene have been formed, which provide more reliability
and less risk to create a new mesh with those materials. On the other hand​, the improvement of
strength profile in the new mesh design minimizes the risk factor of obesity and prior abdominal
surgery. Additionally, reduction of the risk of allergic reaction and inflammation reduces the
chance of recurrence, minimizing the need of secondary operation, and provides a better
postoperative experience.
From an economic perspective, for every 1% of hernia recurrence reduction,
approximately 3.2 million dollars can be saved in hospital costs. To put that into perspective, if
50% of hernia recurrence is eliminated, 48 million dollars will be saved. On the other hand, the
hernia recurrence reduction reduces the need for secondary operation, thereby decreasing the
chance of secondary costs for patients. It releases the financial burden for patients. Hospital
saving and patients saving aside, this new mesh design is projected to capture 0.1%-0.3% of the
every growing hernia market with a compound annual growth rate (CAGR) of 4.6 %. ​The global
hernia repair devices market is expected to generate revenue of around USD 6.2 billion by end of
2024, growing at a CAGR of around 4.6% between 2018 and 2024.​7 The return on investment
will be approximately 1374.2% in 2024.

Project Timeline and Deliverables


The first three months of the program will be dedicated to sourcing Bovine Acellular
Dermal Matrix, Polypropylene, and PLGA as well as purchasing of a sewing machine and Instron

Full Proposal
Materials Selection Competition
High Strength Multi layered Biomesh For Hernia
Repair
LANCE MARX KEITH OSTROWSKI LU SONG IAN MACDOWALL
single column tensile testing machine. Allowing three months for the sourcing of materials will
allow us to find high quality suppliers and perform necessary due diligence for biomedical
supplies. During months 3-9, a material scientist or engineer will be hired as well as a sewing
technician. These two will work together to determine how to wet sew on a sewing machine and
how to perform maintenance on the sewing machine to prevent rust formation and machine
breakdown. After this, the pair will optimize stitch methodology to create stitch patterns with high
tensile strength and high porosity with relatively low polymer counts if possible. During this time,
a patent attorney will be consulted to begin patent application. In month 9, a biologist will be
hired to perform an animal study in a rabbit model with the best designs from months 3-9. Tensile
testing will be performed on a t0 version of the mesh at this point. At 10 months, the animal study
t1 will occur, at which point tensile testing and histological analysis of the mesh will be
performed. At 12 months, the animal study t2 will occur, at which point tensile testing and
histological analysis of the mesh will be performed. Finally, at 15 months, the animal study t3
will occur along with tensile testing and histological analysis. The biologist will then generate a
final report evaluating the tensile and histological performance of the mesh. This will mark the
first milestone of the project. Depending on the outcome of the report it will be determined if
material revisions are necessary, which would kick off additional round(s) of stitch methodology
optimization and animal testing based on the need determined. During years 2-4, additional
testing will be performed as needed while the intellectual property is shopped around to potential
suitors (biomedical companies and hernia mesh companies). Sometime in year 4, patent should be
granted.

Project Cost
A proof of concept can be created with an initial investment of approximately $300,000 in
12 months of time. Funds will be allocated to sewing equipment including a Brother
BAS-311HN-05A sewing machine ($5,000), bobbins, Polypropylene yarn, PLGA yarn and
needles. An Instron 3345 Single Column Tensile Tester will be purchased to perform mechanical
testing (~$25,000). Animal tissue will be sourced from a local abattoir, with total 12 month cost
not to exceed $100,000. One technician will be hired for sewing and one engineer hired for
mechanical testing of prototypes and analysis of gathered data ($100,000 for 6 months salary).
Upon completion of the six month tensile testing period, a patent will be applied for (~$15,000).A
biologist will be hired to perform a histological study in a rabbit model which will be the bulk of
the cost of the project ($40,000 for 6 months salary and $40,000 for animal study). Project costs
will conclude given satisfactory mechanical and histological results in an animal study. If results
are not satisfactory, animal study will need to be repeated an additional time with potential for
multiple iterations, costing additional salary for engineers and technicians to be determined by
number of repeats necessary. The final mesh will cost an estimated $70 to manufacture with $50
going to purchasing Bovine Acellular Dermal Matrix and processing the matrix, and $20 allotted
to pay for polypropylene and poly-lactic co-glycolic acid yarns. The overall mesh cost will be
insignificant compared to research and development costs, and can be sold at a competitive
pricing of $15-20 per square centimeter in a hernia mesh market with biologic hernia meshes
selling for as high as $30 per square centimeter (Strattice/Alloderm).

Full Proposal
Materials Selection Competition
High Strength Multi layered Biomesh For Hernia
Repair
LANCE MARX KEITH OSTROWSKI LU SONG IAN MACDOWALL

References
1. “Hernia Surgical Mesh Implants,” ​Hernia Surgical Mesh Implants – FDA. ​Web. 4 Feb.
2019.<​https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/Implantsand
Prosthetics/HerniaSurgicalMesh/default.htm​>.
2. ​F. Alkhoury, S. Helton, R.J. Ippolito“Cost and clinical outcomes of laparoscopic ventral
hernia repair using intraperitoneal nonheavyweight polypropylene mesh.”, Surgical
Laparoscopy, Endoscopy, and Percutaneous Techniques, vol 21(2) pp 82-5, 2011
3. ​A. Gilpin, Y. Yang ”Decellularization Strategies for Regenerative Medicine: From
Processing Techniques to Applications”, BioMed Research International, vol 7, pp
9831534, 2017
4. ​L-M Zhu, P. Schuster, and U. Klinge, “Mesh implants: An overview of crucial mesh
parameters”, World J Gastrointestinal Surgery, vol 7(10), pp 226-236, 2015
5. ​ASTM Standard D6767-16, “Standard Test Methods for Pore Characteristics of
Geotextiles by Capillary Flow Test,” ASTM International, West Conshohocken, PA,”
2016
6. “PGA, PLA, and PLGA: Functional and Biodegradable Polymers,”​Specific Polymers.
Web. 20 March. 2019.
<​http://specificpolymers.fr/medias/downloads/NEWSLETTER_SEPT_2017.pdf​>
7. "Global Hernia Repair Devices Market Will Reach USD 6.2 Billion by 2024: Zion Market
Research," G ​ lobeNewswire News Room​. Web. 08 Apr. 2019.
<https://globenewswire.com/news-release/2018/07/23/1540674/0/en/Global-Hernia-Repai
r-Devices-Market-Will-Reach-USD-6-2-Billion-by-2024-Zion-Market-Research.html.>
C. R. Deeken and S. P. Lake. “Mechanical Properties of the Abdominal Wall and
Biomaterials Utilized for Hernia Repair,” ​Journal of the Mechanical Behavior of
Biomedical Materials. ​74​ 411-427 (2017).

Full Proposal
Materials Selection Competition
High Strength Multi layered Biomesh For Hernia
Repair
LANCE MARX KEITH OSTROWSKI LU SONG IAN MACDOWALL

Appendix I

Full Budget

Month 1 2 3 4 5 6 7 8 9 10 11 12 Total

Salaries

Sewing
Technician $8,333 $8,333 $8,333 $8,333 $8,333 $8,333 $0 $0 $0 $0 $0 $0 $50,000

Material
Scientist $8,333 $8,333 $8,333 $8,333 $8,333 $8,333 $0 $0 $0 $0 $0 $0 $50,000

Biologist $0 $0 $0 $0 $0 $0 $6,500 $6,500 $6,500 $6,500 $6,500 $6,500 $40,000

Lab
Equipment

Sewing
Machine $10,000 $0 $0 $0 $0 $0 $0 $0 $0 $0 $0 $0 $10,000

Mechanical
Tester $30,000 $0 $0 $0 $0 $0 $0 $0 $0 $0 $0 $0 $30,000

Raw
Materials

BADM $13,333 $13,333 $13,333 $13,333 $13,333 $13,333 $0 $0 $0 $0 $0 $0 $100,000

PP,PLGA,
Needles $2,000 $2,000 $2,000 $2,000 $2,000 $2,000 $0 $0 $0 $0 $0 $0 $12,000

Other

Animal
Testing $0 $0 $0 $0 $0 $30,000 $0 $0 $0 $0 $0 $0 $30,000

Total
Cost $322,000

Full Proposal
Materials Selection Competition
High Strength Multi layered Biomesh For Hernia
Repair
LANCE MARX KEITH OSTROWSKI LU SONG IAN MACDOWALL

Appendix II

Timeline

Month 1 2 3 4 5 6 7 8 9 10 11 12

Task 1
a. Polypropylene
Radii Customization
b. PLGA Radii
Customization
c. Sewing Technique
Customization

Task 2
a. Biaxial Tensile
Test for Mesh
b. Abdominal Forces
Studies and
Comparison

Task 3
a. Animal Testing for
Degradation
b. Animal Testing for
Material Strength
c. Animal Testing for
Histological
Response

Full Proposal
Materials Selection Competition