TIGR Matrix Synthetic Long Term Resorbable Surgical mesh

®

S U R G I C A L M E S H

CORPORATE - timeline

MEDICAL SYSTEMSRadiPlast

1978

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981

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1988

1989

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2011

RadiPlast founded on the basis of usingintelligent plasticmouldings to avoidinjuries to children.

Later the companyturns its’ hand to selling catheter kits.

RadiPlast sold to to CR Bard.RadiPlast becomesagent for ACS (Advanced Catheter Systems).

PressureWire® (Radi Sensor)concept conceived.

First PressureWire® sold. First FemoStop® sold.

PressureWire® methodology ‘Fractional Flow Reserve’ (FFR) conceived.

Radi grows it’s international presence globally with nine regional offices.

Employees around the world swell to 350.

First Femoseal® sold.

Radi acquired by St Jude Medical Inc.

Novus Scientific founded.

Polymer research starts in earnest at the Radi research facility in Uppsala.

The history of Novus Scienti�c - a journey of innovation

Radi Medical Systems AB founded.

Work starts on TIGR™ project.

TIGR®availablein USA.

TIGR®available

in EU.

1978 Engstrom runs radiology product company RadiPlast AB.1982Engstrom secures distribution rights to Advanced Cardiovascular Systems Inc. (ACS > Guidant Inc).1988Engstrom sells RadiPlast AB to CR Bard Inc. and founds Radi Medical Systems AB.1988 – 2008 Radi pioneers some of the world’s leading devices for interventional cardiology, hemostasis management, and radiology. 1999Engstrom sets up a resorbable biomaterials R&D department in Sweden.2003Engstrom invests heavily in clean room production facilities on the island of Phuket.2004Resorbable polymer matrix project group established - 1st patent filed for what would become TIGR® Matrix Surgical Mesh. 2005Engstrom honored at Ernst and Young ’ World Entrepreneur of the Year’ awards.2008Radi Medical Systems sold to St Jude. Inc. / Novus Scientific founded and established into 2009.2010TIGR® Matrix Surgical Mesh launched in the United States.2011TIGR® Matrix Surgical Mesh launched in selected European countries.

TIGR® Matrix Surgical Mesh - indications for use

TIGR® Matrix Surgical Mesh

for use in reinforcement of soft tissue where weakness exists

In January 2010 the US Food and Drug Administration (FDA) gave the company 510(k) clearance to market TIGR® Matrix Surgical Mesh for use in reinforcement of soft tissue where weakness exists.

In July 2011 Novus Scientific’s Quality Management System was certified by BSI to ISO 13485:2003 for the following scope:Design, control of manufacture and supply of sterile resorbable synthetic surgical mesh for reinforcement of soft tissue.

In August 2011 Novus Scientific received CE Mark approval for TIGR® Matrix Surgical Mesh in Europe.

PRODUCT - key features


FAST

SLOW

dual-stage resorption

increasing mechanical compliance

wound healing phase remodeling phase

DECREASING MECHANICAL STRENGTH

INCREASING MECHANICAL COMPLIANCE

long-term absorbable

100% synthetic

0 10 20 30 40 50 60

100

50

* TIGR Matrix Surgical Mesh ** Polyglactin 910*** GTMC

®

WEEKS

% Strength Retention

* Novus Scienti�c, Data on File.

** Chu, C. C. A comparison of the e�ect of pH on the biodegradation of two synthetic absorbable sutures. Annals of Surgery 1982;195(1):55-59

*** Katz et al. New synthetic mono�lament absorbable suture made from polytrimethylene carbonate. Surgery, Gynecology & Obstetrics 1985;161(3):213-222.

strong when you need it gone when you don’t

®


PRODUCT - design


®


Unique, patented dual-fiber construction (dual-stage mechanics)

Strong in the acute wound healing phase

Gradually increasing mechanical compliance over time

Pore size of approx. 1mm at time of implantation increasing to approx 1 x 2mm at 4 months

Warp knitted to prevent unravelling

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PRODUCT - materials


0 days 6 months 3 years

Fast-resorbing fiber = copolymer of glycolide, lactide and trimethylene carbonate. strong for 1-2 weeks, gone in 4 months

Slow-resorbing fiber = copolymer of lactide and trimethylene carbonate. strong for 6-9 months, gone in 3 years

PRODUCT - strength comparison


For six months TIGR® Matrix Surgical Mesh maintains mechanical integrity equivalent to a lightweight polypropylene mesh and initially is twice that strong.

High strength is crucial in the initial wound healing phase. Beyond that the increasing mechanical compliance of TIGR® Matrix is designed to promote remodelling of native tissue.

Physiomechanical Properties of Permanent Meshes compared to TIGR® MatrixDeeken CR, et al. J Am Col Surg. 2011;212:68-79.Deeken CR, et al. Surg Endosc. 2011;25:1541-52.

Data on file: Novus Scientific


10

Product Burst

strength (N/cm)

Strain at 16N/cm

(%)

Suture retention strength,

parallel/perpendicular (N)

Tear resistance, parallel/perpendicular

(N)

Thickness (mm)

TIGR® Matrix

86.5 7.0 45.8 / 59.0 32.0 / 33.3 0.51

Physiologic requirement

32 15-25 ? - -

Ultrapro™ 35.5 16.2 15.1 / 16.7 10.5 / 5.1 0.50

Parietex Composite™

38.9 6.5 28.2 / 36.3 19.7 / 16.2 0.76

C-Qur™ Lite “Small” 50.5 13.2 22.3 / 33.8 19.4 / 18.35 0.28

Proceed™ 52.6 7.25 34.1 / 41.6 19.8 / 20.2 0.57

Gore Dualmesh™ 97.8 10.2 65.2 / 73.0 30.5 / 41.3 1.20

Parietex Flat Sheet TEC™

112.9 3.5 51.4 / 58.4 32.7 / 28.6 0.52

Prolene™ 156.6 5.3 61.2 / 70.5 33.7 / 39.3 0.53

Bard Mesh™

157.7 10.8 50.8 / 66.8 46.8 / 38.4 0.73

-10

PRODUCT - strength retention comparison


Biomechanical Characteristics of Biologic Meshes

89.6

253

317

30 37 35 20 14

23

0

50

100

150

200

250

300

350

Veritas™ Alloderm™ Permacol™

Max Force (N

)

0 Months 1-‐12 Months max 1-‐12 Months min

TIGR® Matrix Surgical Mesh is stronger for much longer than other synthetic absorbable meshes and is designed to have gradually increasing mechanical compliance.

VicrylTM (Polyglactin 910) for example degrades in a matter of 2-3 weeks. The long-term resorption of TIGR® Matrix gives the recipient tissue time to respond to the increasing mechanical load.

0 10 20 30 40 50 60

100

50

* TIGR Matrix Surgical Mesh ** Polyglactin 910*** GTMC

®

WEEKS

% Strength Retention

* Novus Scienti�c, Data on File.

** Chu, C. C. A comparison of the e�ect of pH on the biodegradation of two synthetic absorbable sutures. Annals of Surgery 1982;195(1):55-59

*** Katz et al. New synthetic mono�lament absorbable suture made from polytrimethylene carbonate. Surgery, Gynecology & Obstetrics 1985;161(3):213-222.

TIGR® Matrix Strength Retention compared to other Resorbable Synthetics

TIGR® Matrix Surgical Mesh retains 50% of its mechanical strength for at least 6 months.

Deeken CR, et al .J Am Coll Surg 2011;212:880-888

THE CONCEPT Of MECHaNOTRaNsDUCTION*


“collagen networks are mechanosensitive in that they are stabilized by mechanical strain.”

Muscles and tendons become stronger in response to repetitive loading.

“Tendons adapt to changes in mechanical loading, and numerous animal studies show that immobilization of a healing tendon is detrimental to the healing process.”

*mechanotransduction is the physiological process where cells sense and respond to mechanical loads Br J Sports Med 2009;43:247-252 doi:10.1136/bjsm.2008.054239

PRODUCT - time dependent mechanical characteristics


TIGR® Matrix Surgical Mesh was developed based on the hypothesis that soft tissue positively remodels in response to the stimulus of increased mechanical load.

The increasing mechanical compliance results in a gradual transition of load from the mesh to the patient.

7

15

1920

16.2

6.5

13.2

7.3

10.2

3.5

5.3

10.8

DAY 0


Junge K, et al. Hernia (2001) 5: 113-118.Data on file: Novus Scientific.

wound healing phase remodeling phase

DECREASING MECHANICAL STRENGTH

INCREASING MECHANICAL COMPLIANCE

TIG

R® M

atri

x

TIG

R® M

atri

x (d

ay 2

8)

TIG

R® M

atri

x (d

ay 1

82)

TIG

R® M

atri

x (

day

277)

Ultr

apro

Pari

etex

Com

posi

te

C-Q

ur L

ite S

mal

l

Proc

eed

Gor

e D

ualm

esh

Pari

etex

Fla

t She

et T

EC

Prol

ene

Bard

Stra

in a

t 16N

/cm

(%) required physiological elasticity in vertical stretching (25 ± 7 %)

(day

0)

The elasticity of TIGR® Matrix Surgical Meshincreases over time, reaching normal physiological levels after 6 months.

PRODUCT - why long-term resorbable /absorbable?


Wound healing is a long-term process. In particular, the time taken to regain 50% of normal tissue strength is typically 3 months, after which about 80% of normal tissue strength is ultimately achieved. The time scale can be significantly longer in some patients.

Approximate times of the different phases of wound healing, with faded intervals marking substantial variation, depending mainly on wound size and healing conditions.

(Image does not include major impairments that cause chronic wounds.)

PRODUCT - benefits


TIGR® Matrix Surgical Mesh is: 100% resorbable / absorbable 100% synthetic Strong for 6 months, gone in 3 years (dual-stage mechanics) Easy to handle CE marked

0 days 6 months 3 years

strong when

you need it

gone when you don’t

for 6 months in 3 years

DEfCET CREaTION - 3 year sheep study


Creation of a 4x4 cm full thickness defect (peritoneum left intact) in the abdominal wall of a sheep.

TIGR® M

atrix Surgical Mesh

Mesh repair of the defect performed as onlay using TIGR® Matrix Surgical Mesh trimmed to 8x8 cm secured with interrupted permanent sutures.

This is a summary of the results from a 3 year implantation study of TIGR® Matrix Surgical Mesh in the abdominal wall of sheep.

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HIsTOLOGY GUIDE


Macrophage

Fibroblasts (f)

Blood vessel (V)

Organized (layered) fibroconnective tissueCollagen (C)

Foreign body granuloma

Polypropylene fiber (monofilament)

TIGR® Matrix multifilament bundle

Individual filaments in the multifilament bundle

TIGR® Matrix filament engulfed by giant cell (G) phagocytosis

Visible signs of TIGR® Matrix fiber degradation

Note: regarding foreign body reactionThe foreign body reaction begins as wound healing, including accumulation of exudate at the site of injury, infiltration of inflammatory cells to debride the area, and the formation of granulation tissue.

However, the persistent presence of a biomedical implant, splinter, particulates, or other foreign bodies inhibits full healing. Rather than the resorption and reconstruction that occurs in wound healing, the foreign body reaction is characterized by the formation of foreign body giant cells, encapsulation of the foreign object, and chronic inflammation.

PRECLINICaL - neovascularization at 4 months

TIGR® M

atrix Surgical Mesh


NEOVasCULaRIZaTION

The formation of new blood vessels can clearly be seen within the connective tissue in the vicinity of the implanted mesh fibers.

KEY V - blood vessel

V

PRECLINICaL - 4 & 6 months

INTEGRaTION

Excellent tissue integration of TIGR® Matrix with a well organized, regenerated fibroconnective tissue at 4 months.

mesh fiber bundle

TIGR® M

atrix Surgical Mesh

mesh fiber bundle

(bottom left)TIssUE INGROWTH

Connective tissue infiltrating the synthetic filaments of TIGR® Matrix.

(bottom right)MaCROPOROsITY

TIGR® Matrix fibers under plane polarized light following 6 months implantation. TIGR® Matrix is well integrated into abdominal wall with abundant fibroconnective tissue.

TIGR® M

atrix Surgical Mesh


TIGR® M

atrix Surgical Mesh

PRECLINICaL - 9 months


TIssUE GENERaTION

Staining for collagen type I (orange) and III (green) in TIGR® Matrix (A-B) and Polypropylene (C-D) meshes following 9 months implantation.

A

C

TIGR®

PP PP

TIGR® B

TIGR®

FIBERS

TYPE I

TYPE I

TYPE III

PPFIBERS

TYPE I

TYPE III

PPFIBER

TIGR®

FIBERS

TYPE I TYPE III

D



fULL THICKNEss REPaIR

TIGR® Matrix showing excellent tissue integration and thick repair tissue as compared to polypropylene control mesh.

TIGR® Matrix Surgical MeshControl Mesh

(bottom left)

CONTROL

Polypropylene fibers of the control mesh surrounded by granulomas and collagen (the quantity of collagen is lower and typically ingrowth between fibers is not seen to the same extent). G

V

KEY V - blood vessel G - giant cell

Control Mesh

(bottom right)

aBUNDaNT COLLaGEN

Ordered connective tissue ingrowth (C) between two TIGR® Matrix multifilament bundles. Collagen is abundant and the inflammatory response is low.

TIGR® M

atrix Surgical Mesh

C

KEY C - collagen



sEM - TIGR® Matrix

Full thickness abdominal wall with TIGR® Matrix well integrated within a thick surrounding fibroconnective tissue.

sEM - POLYPROPYLENE CONTROL

Full thickness abdominal wall with polypropylene fibers integrated within a thin surrounding fibroadipose tissue.

REG

ENER

aTED

CO

NN

ECTI

VE

TIss

UE

fIB

RO-

aD

IPO

sE

TIss

UE

Control Mesh

TIGR® M

atrix Surgical Mesh



DEGRaDaTION

TIGR® Matrix filaments surrounded by giant cells which have engulfed

fibers, indicating an ongoing process of degradation.

Collagen fibers are infiltrating the mesh.

Sections of degrading filament

TIGR® M

atrix Surgical Mesh

C

KEY C - collagen G - giant cell

G

TIssUE REGENERaTED

TIGR® Matrix after two years of implantation.

Repair tissue is thick and well vascularized.

Only the permanent sutures reveal the

original location of the mesh and defect.



TIGR® M

atrix Surgical Mesh

TIssUE REsTORED

Three years after the surgery, results show a nicely restored abdominal wall without signs of the original defect

(view from the peritoneal side).

COLLaGEN fORMaTION

TIGR® Matrix is absorbed and replaced by abundant collagen.

Few inflammatory cells remaining and no foreign body reaction can be seen.

Fibroblasts distributed within well organized connective tissue.


data on file Novus Scientific


TIGR® Matrix macroscopically invisible 3 years post implant. Only permanent sutures remain and are visible.

TIGR® Matrix has been completely replaced by thicker, healthy connective tissue (neo-fascia).

Comparison between TIGR® Matrix & polypropylene as seen in a 3 year sheep model

Polypropylene mesh encapsulated and delaminated from tissue after 3 years. (clearly visible).

At 36 months Polypropylene mesh still elicits an inflammatory response.


TIGR® Matrix - published evidence

As stated in the publication: “As the resorbable test mesh gradually degraded it was replaced by a newly formed collagen matrix with an increasing ratio of collagen type I/III, indicating a continuous remodeling of the collagen towards a strong connective tissue.” Furthermore: “The general connective tissue layer formed was thicker around the test mesh compared to the control.”

Hjort H, Mathisen T, Alves A, et al. (2011) Three-year results from a preclinical implantation study of a long-term resorbable surgical mesh with time-dependent mechanical characteristics. Hernia. doi: 10.1007/s10029-011-0885-y

a B

Fig. B - Collagen type I/III ratio as a function of time following implantation.

(symbols mean values, bars standard deviation).Fig. A - Total collagen content as a function of time following implantation.(symbols mean values, bars standard deviation).

TIGR® Matrix - first in man


40 patients with primary inguinal hernias.Enrolled in 2 Swedish hospitals March-Dec 2009.Clinical outcome assessed 0.5, 1, 3, 6 & 12 months.Preliminary follow-up presented March 2009, AHS, Orlando.All patients followed a normal postoperative course.No serious adverse events and only one recurrence after 12 months.Three patients experienced mild pain (VAS<10) after 12 months.Only 4 patients could feel the presence of a mesh in their groin after 12 months.

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INGUINaL HERNIa

World Cup Speedsurfer and TIGR® Matrix

recipient (Dec 2009) Martin Lamm was back

on his board after 12 weeks and competing

within 5 months.Gothenburg, Sweden

TIGR® Matrix - in action


54 year old male. Necrotizing pancreatitis in 2009. Multiple abdominal operations resulted in open abdomen necessitating skin graft over bowel. Presented one year later with large ventral hernia defect and obvious skin graft deformity.

TIGR® Matrix Surgical Mesh was used as an alternative to permanent synthetic mesh because permanent synthetic mesh can require mesh removal in the setting of a post operative wound infection.

TIGR® Matrix Surgical Mesh performed well with excellent short-term outcomes in a complex patient with high risk of wound complications.

SURGEON HOSPITAL LOCATION BRUCE RAMSHAW, MD, FACS Halifax Health Daytona Beach, FL USA

PROCEDURE

Endoscopic bilateral component separation enforced with TIGR® Matrix Surgical Mesh

TIGR® Matrix - in action


In December 2010 a 50 year-old female executive was diagnosed with left breast carcinoma. She subsequently underwent an elective left skin sparing mastectomy and reconstruction with an ipsilateral transverse rectus abdominis myocutaneous (TRAM) flap.

Following elevation of the TRAM flap, the abdominal donor site is closed primarily with PDS 1 suture. A TIGR® Matrix Surgical Mesh is used as an onlay mesh to reinforce the closure. It is anchored with a PDS 2/0 and 3/0 continuous stitches.

Conclusion:

Being fully resorbable, there is a potential benefit of reduced long term complication associated with permanent implants.

SURGEON HOSPITAL LOCATION YAN LIN YAP, MBBS, FAMS National University Hospital Singapore

PROCEDURE The use of TIGR® Matrix Surgical Mesh for closure of abdominal donor site following

transverse rectus abdominis myocutaneous flap for breast reconstruction.

Primary repair with PDS1 Onlay TIGR® Matrix.

TIGR® Matrix used to reinforce primary repair of rectus sheath

TIGR® Matrix - contraindications


Not suitable for reconstruction of cardiovascular defects.TIGR® Matrix Surgical Mesh must always be separated from the abdominal cavity by peritoneum.Not for use following planned intra-operative or accidental opening of the gastrointestinal tract. Use in these cases may result in contamination of the mesh, which may lead to infection.

RX ONLY - Read Instructions for Use which accompany the product for indications, contraindications,

warnings and precautions.

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TIGR® Matrix - summary of preclinical testing


Test Standard / Method Conclusion

Cytotoxicity ISO 10993/USP MEM elution method Passed. No evidence of causing cell lysis or toxicity. Grade: 0.

Delayed dermal contact sensitization

ISO 10993/Maximization method Passed. No delayed sensitization in guinea pig. Grade:0.

Intracutaneous irritation ISO 10993/Intracutaneous injection in rabbit Passed. The irritation index: 0 for the 0.9% NaCl extract; 0.08 for the sesame oil extract (lower than 1)

Acute systemic toxicity ISO 10993/Injection in mouse Passed. No evidence of significant systemic toxicity or mortality.

Genotoxicity ISO 10993/Ames test Passed. Test article extracts were not toxic or mutagenic.

Genotoxicity ISO 10993/Chromosomal aberrations induction in human cells

Passed. Test article extract did not induce chromosomal aberrations in human lymphocytes.

Pyrogenicity USP 30-NF25 Passed. Non-pyrogenic.

Implantation study in rats; 1, 3 & 6 months follow-up

ISO 10993 Passed. Good local tolerance.

Implantation study in sheep; 4, 9, 15, 24, & 36 months follow-up

ISO 10993 Passed. Good overall biocompatibility.

2C

25C

T

YVEK

TYVEKNONSTERILE

ON OUTSIDE

STERILIZE2

RX ONLY – Before using TIGR® Matrix Surgical Mesh read the instructions for use which accompany the product for indications, contraindications, warnings and precautions.

INDICaTIONs fOR UsETIGR® Matrix Surgical Mesh is intended for use in reinforcement of soft tissue where weakness exists.

CONTRaINDICaTIONsNot suitable for reconstruction of cardiovascular defects. TIGR® Matrix Surgical Mesh must always be separated from the abdominal cavity by peritoneum. Not for use following planned intra-operative or accidental opening of the gastrointestinal tract. Use in these cases may result in contamination of the mesh, which may lead to infection.

063M-03

TIGR Matrix Synthetic Long Term Resorbable Surgical mesh

Healthcare

Transcript of TIGR Matrix Synthetic Long Term Resorbable Surgical mesh