Points of Strength

-e Collagen Matrix for Hernia Repair

POINTS OF STRENGTH for Hernia Repair Proven Strength Integration Lasting Repair Clinical Data Source & Processing Product Options IMPORTANCE OF STRENGTH SurgiMend® is offered in thickness of 1mm, 2mm, 3mm and 4mm. Even at 1mm thickness, SurgiMend has been shown to have the strongest uniaxial tensile strength when compared to other major competitors.1

5 Uniaxial Tensile Stress (Mpa) Tensile Uniaxial

0 Surgisis®, SurgiMend Straice™, XenMatrix™ AlloMax™ X-Thick FlexHD® Veritas® Peri-Guard® CollaMend™ CollaMend Permacol™ Biodesign® Firm AlloDerm® FM

An MD Anderson study comparing mechanical properties of ADMs derived from bovine and porcine dermis found 3mm and 4mm thick SurgiMend:

• To be as strong as the stainless steel suture2 Tear Resistance Thickness Maximum Load ® ™ • To haveSurgiMend twice the suture retentionStrattice of (mm), SD (N), SD porcine dermal matrix (2mm thick)2 PADM* 1.75 + 0.14 19.66† + 3.90

** † • To be more than twice as resistant to tearing BADM 2.0 1.85 + 0.27 50.95 + 11.79 as porcine dermal matrix2 BADM 3.0 3.23 + 0.54 86.89† + 15.34 BADM 4.0 3.83 + 0.32 100.02† + 14.28

* PADM: Porcine Acellular Dermal Matrix ** BADM: Bovine Acellular Dermal Matrix † Significant difference from all other conditions by 1-way analysis of variance and Tukey post hoc analysis (P < 0.05).

• SurgiMend’s increased resistance to tearing is papillary dermis related to the bovine dermal source material2,3

• Bovine and porcine dermis have significant 3

reticular dermis differences in collagen fiber weave pattern

• Unlike bovine dermis, hair follicles perforate

hypodermis 4 Bovine Porcine the entire dermis in porcine skin INTEGRATION & REVASCULARIZATION SurgiMend is rapidly revascularized to support tissue building and healing for prolonged reinforcement.5,6

11 ½ Months: Revascularized SurgiMend 11 ½ months after hernia repair in a patient undergoing a subsequent procedure unrelated to the original hernia repair.

Photo Credit: Simone, M.V. New York: Columbia Presbyterian Hospital

6 Months: Revascularized SurgiMend 6 months after incisional hernia repair in a patient with Crohn’s disease during re-exploration for a second procedure unrelated to the original hernia repair.

Photo Credit: Rivadeneira DE. Smithtown (NY): St Catherine of Siena Medical Center 2012

SurgiMend revascularizing in a small animal intra-abdominal implant model. SurgiMend did not trigger a detrimental foreign-body inflammatory response that would lead to rapid degradation or encapsulation.7 LONG LASTING HERNIA REPAIR8-10 A persistent, thick, well-vascularized connective tissue was imaged more than two years post-operatively in SurgiMend reinforced hernia repairs.11

Flank Hernia Ventral Hernia 26 months 22 months

SurgiMend (appears white)

All photos courtesy of Dr. Adelman

50 BFC only reinforced Repair only control 40

Load (N) 20

0 10 20 30 40 50 Time (weeks)

*BFC: Bovine Fetal Collagen • Demonstrated maintenance of hernia reinforcement strength in a small animal model through 1 year6

• Persistence of a host cell populated, well vascularized, connective tissue in a small animal model, consistent with clinical CT patient imaging6

Reprinted from Journal of Surgical Research, Vol. 201/issue 2, Cornwell KG, Zhang F, Lineaweaver W, Bovine Fetal Collagen Reinforcement in a Small Animal Model of Hernia with Component Repair, 416-424; 2016, with permission of Elsevier STRONG CLINICAL DATA Numerous retrospective clinical studies have reported on hernia repair outcomes with SurgiMend reinforcement. Low hernia recurrence was shown with the use of SurgiMend.

SurgiMend Hernia Study Materials Studied Recurrence Rate

Clemens et al.8 3.9% SurgiMend, Strattice

Lineaweaver12 6.6% SurgiMend, AlloDerm and Surgisis

Janafaza et al.13 5% SurgiMend and FlexHD

Booth et al.9 5.8% SurgiMend, Strattice and AlloDerm

Garvey et al.10 6.7% SurgiMend, Strattice and AlloDerm

Soares et al.14 6% SurgiMend and Prolene® with hybrid NPWT

INTRAOPERATIVE DEVICE FAILURES

A complex abdominal wall reconstruction study by MD Anderson found a 0% vs 10% intraoperative device failure rate when comparing SurgiMend acellular dermal matrix to a porcine acellular dermal matrix.8 PROPRIETARY SOURCE AND PROCESSING The only biologic mesh composed of fetal or neonatal bovine dermal collagen, SurgiMend consists of an array of distinct interwoven collagen fibers with ample porosity to allow for rapid cell repopulation and vascularization.1,5,6,15

• Abundance of Type III Collagen (20-30%)16-20

• Type III Collagen is the first type of collagen synthesized during both embryonic development and wound healing16-20

Manufactured from fetal or neonatal bovine dermis using a patented processing method that:

REMOVES cells, lipids, carbohydrates, and other constituents that can induce inflammation

PRESERVES the beneficial properties of the natural collagen matrix in a native undamaged state SurgiMend is readily populated by host STERILIZES via exposure to ethylene oxide gas for a cells upon implantation. Blood vessels -6 (red, indicated by the arrows) also sterility assurance of 10 with undetectable ethylene penetrate the collagen matrix (blue) to oxide residuals meet the metabolic requirements of the tissue.5,15 3.0 4.0

2.0

1.0

FLEXIBLE OPTIONS TO MEET PATIENTS NEEDS SurgiMend is offered in 1.0mm, 2.0mm, 3.0mm, and 4.0mm thicknesses, providing surgeons with the widest flexibility to choose the most appropriate device thickness, strength, and size for each procedure, technique, and patient.

• Over 65 sizes and configurations • Sizes up to 25cm x 40cm The biological make-up of bovine dermis, including its inherent collagen fiber architecture, make SurgiMend particularly strong.1,2,3,15 SurgiMend hydrates rapidly in room temperature saline. Trimming can be done in both its dry and hydrated state. Once fully hydrated, the material is pliable and compliant, readily conforming to the surgical site.

Description Warnings and Precautions • The patient’s medical condition may adversely impact healing of the deficient SurgiMend is an acellular dermal tissue matrix CAUTION: FEDERAL LAW (USA) RESTRICTS tissue. These conditions may include, but are derived from bovine dermis. The device is THIS DEVICE TO SALE BY OR ON THE ORDER not limited to: smoking, diabetes, insufficient supplied sterile in a variety of sizes to be OF A PHYSICIAN. blood supply at the implant site, and trimmed by the surgeon to meet the individual • Consider the loading environment when exposure of the implant site to radiotherapy. patient’s needs. selecting the product thickness; thicker • General risks may include, but are not limited Indications product tends to have greater initial strength. to: infection, allergic reactions, pain, swelling SurgiMend is intended for implantation to • Fenestrated product will stretch more than or bruising, foreign body reaction, acute or reinforce soft tissue where weakness exists and nonfenestrated product. chronic inflammatory reactions, adhesions, for the surgical repair of damaged or ruptured • SurgiMend should be used with caution seroma, hematoma, and repair laxity. The soft tissue membranes. where any pre-existing pathology may limit patient should be made aware of these risks blood supply and compromise healing. and others associated with general surgery SurgiMend is specifically indicated for: and the use of anesthesia. • Treat any existing infection appropriately • Plastic and reconstructive surgery with local and/or systemic antibiotics in an • Muscle flap reinforcement attempt to eliminate infection. If used in • Hernia repair including abdominal, inguinal, contaminated or infected wounds collagen- femoral, diaphragmatic, scrotal, umbilical, based implants can weaken or break down if and incisional hernias exposed to bacterial enzymes. • SurgiMend should be used with caution in Contraindications surgical locations where the product may • SurgiMend is not designed, sold, or intended be exposed to stomach and/or intestinal for use except as indicated. contents. Collagen-based implants can be • SurgiMend should not be used in patients susceptible to degradation by digestive with a known history of hypersensitivity to enzymes and conditions of acidic (low) pH. collagen or bovine products. • SurgiMend has not been evaluated in pregnant women.

References

1. Deeken CR, Eliason BJ, Pichert MD, et al. Differentiation of Biologic Scaffold Materials Through Physicomechanical, Thermal, and Enzymatic Degradation Techniques. Ann Surg. 2012; 00(0) 2. Adelman DM, Selber JC, Butler CE. Bovine versus Porcine Acellular Dermal Matrix: A Comparison of Mechanical Properties. Plast Reconstr Surg Glob Open. 2014;2(5):e155. 3. Wells HC, Sizeland KH, Kirby N, Hawley A, Mudie S, Haverkamp RG. Collagen Fibril Structure and Strength in Acellular Dermal Matrix Materials of Bovine, Porcine, and Human Origin. ACS Biomater Sci Eng. 2015;1(10):1026-1038. 4. Mowafy M, Cassens R. Microscopic structure of pig skin. J Anim Sci. 1975;41(5):1281. 5. Cornwell K et al. A generative tissue fabricated with SurgiMend has a mesothelial lining limiting adhesion formation in a model of large ventral hernia repair. Presented at the meeting of the American Hernia Society, Orlando, FL, March 2010. 6. Cornwell KG, Zhang F, Lineaweaver W. Bovine fetal collagen reinforcement in a small animal model of hernia with component repair. J Surg Res. 2016;201(2):416-424. 7. Adelman DM, Cornwell KG. Analysis of adherence and vascularization patterns of bioprosthetic mesh compared to synthetic mesh in a rat intra-abdominal implant model. Presented at the Abdominal Wall Reconstruction Conference, Washington, DC, June 2014. 2013. 8. Clemens M, Selber J, Liu J, et al. Bovine versus porcine acellular dermal matrix for complex abdominal wall reconstruction. Plast Reconstr Surg. 2012 Jul;130(1S): 9. Booth JH, Garvey PB, Baumann DP, et al. Primary fascial closure with mesh reinforcement is superior to bridged mesh repair for abdominal wall. J Am Coll Surg. 2013. 10. Garvey PB, Martinez RA, Baumann DP, et al. Outcomes of Abdominal Wall Reconstruction with Acellular Dermal Matrix Are Not Affected by Wound Contamination. J Am Coll Surg. 2014;219(5):853-864 11. Adelman DM. Radiographic evaluation of biologic mesh repair in ventral abdominal herniorrhaphy. Presented at the American College of Surgeons (ACS) Annual Clincal Congress. Washington DC; 2013. 12. Lineaweaver W. Improvement of success rates for abdominal component reconstructions using bovine fetal collagen. Ann Plast Surg. 2012;68(5):438–41 13. Janfaza M, Martin M, Skinner R. A preliminary comparison study of two noncrosslinked biologic meshes used in complex ventral hernia repairs. World J Surg. 2012;36(8):1760–4. 14. Soares KC, Baltodano PA, Hicks CW, et al. Novel wound management system reduces surgical site morbidity after ventral hernia repairs: a critical analysis. Am J Surg. August 2014. 15. Cornwell KG, Landsman A, James KS. Extracellular Matrix Biomaterials for Soft Tissue Repair. Clin Podiatr Med Surg. 2009;26(4):507-523. 16. Barnes M, Morton L, Bennet R, et al. Presence of type III collagen in guinea- pig dermal scar. Biochemical Journal 1976;157:263-266. 17. Epstein E. [a1(III)]3 Human Skin Collagen: Release by pepsin digestion and preponderance in fetal life. Journal of Biological Chemistry 1974;249:3225-3231. 18. Smith LT, Holbrook KA, Madri J. Collagen types I, III and V in human embryonic and fetal skin. The American Journal of Anatomy 1986; 175:507-521. 19. Sykes B, Puddle B, Francis M, Smith R. The estimation of two collagens from human dermis by interrupted gel electrophoresis. Biochemical and Biophysical Research Communications 1976;72:1472- 1480. 20. Ramshaw J. Distribution of type III collagen in bovine skin of various ages. Connective Tissue Research 1986;14:307-314.

Availability of these products might vary from a given country or region to another, as a result of specific local regulatory approval or clearance requirements for sale in such country or region. n Always refer to the appropriate instructions for use for complete clinical instructions. n Non contractual document. The manufacturer reserves the right, without prior notice, to modify the products in order to improve their quality. n Warning: Applicable laws restrict these products to sale by or on the order of a physician.

For more information or to place an order, please contact: Manufacturer: United States, Canada, Asia, Pacific, Latin America TEI Biosciences Inc. 7 Elkins Street USA 866-524-0022 n 888-623-2259 fax Boston, MA 02127 n USA International +1 617-268-1616 n +1 617-268-3282 fax [email protected]

SurgiMend, Integra and the Integra logo are registered trademarks of Integra LifeSciences Corporation or its subsidiaries in the United States and/or other countries. TEI Biosciences Inc. is a subsidiary of Integra LifeSciences Corporation. Surgisis and Biodesign are registered trademarks of Cook Medical Inc. AlloDerm is a registered trademark of LifeCell Corporation. Strattice is a trademark of LifeCell Corporation. XenMatrix, CollaMend and AlloMax are trademarks of C.R. Bard Inc. FlexHD and Prolene are registered trademarks of Ethicon USA, LLC. Veritas is a registered trademark of Baxter Healthcare Corp. Peri-Guard is a registered trademark of Synovis Life Technologies Inc. Permacol is a registered trademark of Covidien. ©2016 Integra LifeSciences Corporation. All rights reserved. Printed in USA. 0498039-2-EN