Dermamatrix Acellular Dermis. Human Dermal Collagen Matrix

DermaMatrix Acellular Dermis. Human dermal collagen matrix.

Rehydrates quickly

Does not require refrigerated storage

Bacterially inactivated DermaMatrix Acellular Dermis

DermaMatrix Acellular Dermis is processed by the Epidermis Musculoskeletal Transplant Foundation (MTF) and is available through Synthes CMF.

DermaMatrix tissue is an allograft derived from donated human skin. The epidermis and dermis are removed from the subcutaneous layer of the skin during the recovery procedure. The tissue is then processed using a sodium Dermis chloride solution and detergent to remove the epidermis and all viable dermal cells while maintaining the original dermal collagen matrix. The cells are removed to minimize Subcutaneous layer inflammation or rejection at the surgical site. Normal human skin DermaMatrix Acellular Dermis is then treated in a disinfection solution that combines detergents with acidic and antiseptic reagents to further clean the tissue so that it passes the United States Pharmacopeia Chapter 71 (USP <71>) for sterility. Finally, it is cut to size, freeze-dried and packaged in a terminally sterilized double pouch and envelope.

When ready for use, DermaMatrix tissue should be rehydrated in at least 100 ml of sterile, room temperature saline or DermaMatrix 3D Collagen Matrix lactated Ringer’s solution. It will typically rehydrate to a uniformly soft and pliable consistency. Rehydration time is dependent on the thickness and size of the graft. Additional Transplanted rinsing to remove any residuals is not needed. Acellular Dermis

After DermaMatrix Acellular Dermis is transplanted into the Fibroblasts patient, host cells begin to infiltrate the three-dimensional collagen matrix. The patient’s blood vessels revascularize the implant and fibroblasts are incorporated into the matrix.

Blood vessels Remodeled skin

white indicates absence of cells Epidermis Collagen

Viable cells Dense collagen matrix

Human tissue, with cells intact DermaMatrix, with cells removed (200X magnification) (200X magnification)

Synthes 1 DermaMatrix Acellular Dermis continued

Features – Rehydrates quickly* – Is aseptically processed and passes USP <71> for sterility. The tissue is bacterially inactivated by the disinfection process, which reduces the level of bacteria, spores, fungi, mold and yeast – Does not require refrigeration—freeze-dried tissue can be stored at ambient temperature – Minimizes the amount of autograft needed – Non-cross-linked – Allows revascularization and cell repopulation in the three-dimensional collagen matrix for normal tissue DermaMatrix tissue is notched so that when positioned as shown remodeling** (with the notch in the upper left corner), the epidermal side of – Minimizes inflammation or rejection at the surgical site, the tissue (basement membrane) is facing up. as a result of the tissue processing which removes viable cells and antigens – Has a three-year shelf life – Has 90% consistency of thickness across the length of the tissue

* Reconstitution time may vary with size and thickness of the tissue, temperature of saline or lactated Ringer’s solution and/or donor’s tissue property. ** Acellular Dermal Matrix. MTF internal report summarizing test results of Acellular Dermal Matrix on biomechanical properties, histological profile, structural analysis, preclinical evaluation and tissue safety.

2 Synthes DermaMatrix Acellular Dermis Clinical Applications

DermaMatrix tissue is for homologous use only. Homologous use as defined by the FDA is: The replacement or supplementation of a recipient’s tissue with a tissue form that performs the same basic function or functions in the recipient as in the donor.

Clinical applications include, but are not limited to, the following: – Parotidectomy – Tympanoplasty Breast reconstruction Oral cavity repair – Facial soft tissue defects postmastectomy – Facial sling – Lower eyelid reconstruction – Nasal reconstruction – Nasal septal perforation – Cleft palate repair – Oral resurfacing – Vestibuloplasty – Radial forearm freeflap repair – Breast reconstruction postmastectomy – Abdominal wall repair Nasal septal perforation Abdominal wall repair

Indications DermaMatrix tissue is processed to remove cells while maintaining the integrity of the matrix with the intent to address the issues of the specific and nonspecific inflammatory responses. It is used for the replacement of damaged or inadequate integumental tissue or for the repair, reinforcement or supplemental support of soft tissue defects.

Contraindications Use of DermaMatrix tissue in patients exhibiting autoimmune connective tissue disease is not recommended. – Specific or nonspecific immune response to some component of the graft

Please refer to the package insert for additional precautions and adverse effects.

Synthes 3 Tissue Properties

Biomechanical properties** Tensile strength of acellular dermis

DermaMatrix tissue has been subjected to biomechanical 100 DermaMatrix tissue (N=29) testing to characterize its physical properties. Testing was 90 AlloDerm (N=12) conducted by MTF, in accordance with MTF established 80 procedures and ASTM International standards, for mechanical 70 63.2 strength and ability to hold suture. Test results were compared 60 to the properties of a leading competitive dermal matrix 50 material. 44.2 40

30 DermaMatrix Acellular Dermis demonstrates superior 20 14.6 biomechanical properties in comparison with the leading 10 8.0 competitor’s dermal matrix material. It exhibits an average 0 2 tensile strength, an intrinsic property, of 14.6 N/mm and Tensile strength Peak load 2 can withstand an average maximum load of 63.2 N prior (N/mm ) (N) to yielding. The competitor’s material, when subjected to Tensile modulus of acellular dermis the same testing, exhibited an average tensile strength of 18 8.0 N/mm2 and a maximum load before yield of 44.2 N. DermaMatrix tissue (N=29) 16 AlloDerm (N=12) The average elastic modulus, or ability of DermaMatrix 14 tissue to resist deformation, is 8.8 MPa, compared to 12

5.8 MPa for the competitor’s matrix. 10 8.8

8 Suture retention testing showed that DermaMatrix tissue 5.8 6 is equivalent to the competitor’s material. 4 These biomechanical properties are significant when considering 2 applications, such as abdominal wall repair, where material 0 Modulus strength and stiffness are required to promote healing and (MPa) prevent additional failures at the wound repair site. DermaMatrix Acellular Dermis demonstrates a higher tensile modulus, or greater resistance to stretching and deformation in laboratory testing.

For additional information on DermaMatrix properties, Suture retention strength of acellular dermis please refer to the “DermaMatrix Acellular Dermis 50 DermaMatrix tissue (N=26) Comparative Testing” brochure. 45 AlloDerm (N=6)

5 2.9 2.9 0 Suture retention (MPa) DermaMatrix Acellular Dermis shows higher biomechanical strength than the ** Acellular Dermal Matrix. MTF internal report summarizing test results of leading competitor’s material. Tensile strength data (top) and suture retention Acellular Dermal Matrix on biomechanical properties, histological profile, strength (bottom) are shown. structural analysis, preclinical evaluation and tissue safety.

4 Synthes DermaMatrix Acellular Dermis Histological profile DermaMatrix Acellular Dermis has been processed to remove cells while maintaining histomorphological integrity. Standard histology and immunohistochemical methods have been used to assess the dermal matrix structure and its components. Hematoxylin and eosin staining of normal human skin and DermaMatrix tissue show that the Hematoxylin and eosin staining of normal skin (left) and DermaMatrix Acellular Dermis (right) from the same donor. Note absence of cells and matrix is preserved during processing preservation of matrix structure after processing. and demonstrates an absence of the epidermis and cells in the resulting matrix.

Using immunohistochemical staining methods, Types I and III collagen and elastin were evaluated in DermaMatrix Acellular Dermis. The collagen components are not affected during processing, demonstrated by consistent staining throughout the matrix. Immunohistochemical staining shows Type I collagen in normal skin (left) Elastin fibers also remain present after and staining in DermaMatrix Acellular Dermis (right). processing, as seen by darkly stained strands throughout the acellular dermal matrix. Elastin, in conjunction with collagen, contributes to the strength and structure of the dermal matrix scaffold.

Immunohistochemical staining shows Type III collagen in normal skin (left) and staining in DermaMatrix Acellular Dermis (right).

Immunohistochemical staining shows elastin in normal skin (left) and in DermaMatrix Acellular Dermis (right).

All histology courtesy of Premier Laboratory, LLC.

Synthes 5 Tissue Properties continued

Histological profile continued Alcian blue staining reveals that hyaluronan, a major glycosaminoglycan, is present in the tissue. Glycosaminoglycans and glycoproteins, such as hyaluronan and vitronectin, are integral components of the extracellular matrix and play an important role in cell-cell and cell-matrix interactions.1,2,3 Hyaluronan is present in all living organisms and provides matrix structure and osmotic balance, and assists with cell migration and differentiation.4,5 Vitronectin, an adhesive glycoprotein, binds to collagen, and promotes cell attachment, Immunohistochemical staining using Alcian Blue/PAS shows the proliferation, and differentiation.6 presence of hyaluronan in normal skin (left) and in acellular dermal matrix (right) as indicated by indigo staining. Immunohistochemical evaluation of the acellular dermal matrix confirms that the major components of the extracellular matrix, including collagen, elastin, and major matrix components responsible for promoting cell attachment and growth, are preserved after processing. Cells are effectively removed, leaving the original dermal matrix architecture intact.

Immunohistochemical staining shows vitronectin in normal skin (left) and in acellular dermal matrix (right) as indicated by brown staining.

1. Potter MJ, Linge C, Cussons P, Dye JF, Sanders R. “An investigation to optimize angiogenesis within potential dermal replacements.” Plast Reconstr Surg. 2006 May;117(6):1876-85. 2. Fernandez-Botran R, Gorantla V, Sun X, Ren X, Perez-Abadia G, Crespo FA, Oliver R, Orhun HI, Quan EE, Maldonado C, Ray M, Barker JH. “Targeting of glycosaminoglycan-cytokine interactions as a novel therapeutic approach in allotransplantation.” Transplantation. 2002 Sep 15; 74(5):623-9. 3. Schleicher I, Parker A, Leavesley D, Crawford R, Upton Z, Xiao Y. “Surface Modification by Complexes of Vitronectin and Growth Factors for Serum-Free Culture of Human Osteoblasts.” Tissue Engineering. 11(11-12):1688 (2005). 4. Cohen M, Joester D, Geiger B, Addadi L. “Spatial and Temporal Sequence of Events in Cell Adhesion: From Molecular Recognition to Focal Adhesion Assembly.” Chembiochem. 2004 Oct 4;5(10):1393-9. 5. Turley, EA, Noble PW, Bourguignon LY. “Signaling properties of hyaluranon receptors.” J Biol Chem. 2002 Feb 15; 277(7):4589-92. 6. Rosso F, Giordano A, Barbarisi M, Barbarisi A. “From cell-ECM interactions to tissue engineering.” J Cell Physiol. 2004 May;199(2):174-80.

6 Synthes DermaMatrix Acellular Dermis Structural analysis Structural analysis of acellular dermis using high power transmission electron microscopy reveals that the collagen and elastin components of the extracellular matrix are preserved after processing. Collagen in normal skin is observed in the cross section while in the acellular dermis, the fibers are observed oriented in the transverse direction. Elastin appears as an amorphic structure in both sections. Higher magnification reveals normal periodicity of collagen fibrils in the specimens. TEM analysis shows amorphic elastin and fibrous collagen structures in normal skin (left) and acellular dermis (right).

Higher magnification shows collagen fibrils in normal skin (left) and acellular dermis (right).

Microscopy courtesy of Structure Probe, Inc.

Synthes 7 Musculoskeletal Transplant Foundation (MTF)

Synthes has partnered exclusively with the Musculoskeletal MTF’s standards are set by Transplant Foundation (MTF) for over 10 years to provide their Medical Board of Trustees — high quality tissue for patients. Although there are national more than 40 surgeons from standards for tissue banks, they only set a baseline for the world-renowned academic institutions. industry. Beyond that, regulations leave a lot to interpretation, so standards vary significantly from tissue bank to tissue bank. MTF offers safe allografts processed from among the most carefully selected donors.

Directed by Surgeons MTF utilizes a Medical Board of Trustees comprised of more than forty surgeons from world-renowned academic institutions. MTF’s board sets standards, which are among some of the most stringent in the industry.

Selecting the Ideal Donor MTF’s extensive network of participating organ procurement organizations ensures that MTF has access to a broad selection of qualified donors. MTF holds itself to stringent MTF Donor Deferral Rate standards for donor selection and processing criteria. MTF > 97% < 3% defers more donors than they accept. deferred accepted

Preserving and Protecting Tissue Integrity MTF’s approach ensures a high level of safety, without compromising biological and mechanical integrity. Not all forms of human tissue are the same, nor should they be processed the same way. MTF has developed and validated several tissue cleaning technologies to provide safe and high quality allograft bone. Since MTF’s inception, MTF has maintained an exemplary safety record distributing more than 5 million allografts from over 90,000 donors.

8 Synthes DermaMatrix Acellular Dermis Product Information

DermaMatrix Tissue Tissue Code Description Thickness Code Description Thickness Ultra Thin Ultra Thick 019102 1 cm x 2 cm 0.2 mm–0.4 mm 012510 5 cm x 10 cm ≥1.8 mm 019204 2 cm x 4 cm 0.2 mm–0.4 mm 012412 4 cm x 12 cm ≥1.8 mm 019407 4 cm x 7 cm 0.2 mm–0.4 mm 012612 6 cm x 12 cm ≥1.8 mm 012416 4 cm x 16 cm ≥1.8 mm Thin 012616 6 cm x 16 cm ≥1.8 mm 010101 1 cm x 1 cm 0.4 mm–0.8 mm 012816 8 cm x 16 cm ≥1.8 mm 010102 1 cm x 2 cm 0.4 mm–0.8 mm 012122 12 cm x 12 cm ≥1.8 mm 010202 2 cm x 2 cm 0.4 mm–0.8 mm 012016 10 cm x 16 cm ≥1.8 mm 010104 1 cm x 4 cm 0.4 mm–0.8 mm 012216 12 cm x 16 cm ≥1.8 mm 010204 2 cm x 4 cm 0.4 mm–0.8 mm 012206 6 cm x 20 cm ≥1.8 mm 010307 3 cm x 7 cm 0.4 mm–0.8 mm 012208 8 cm x 20 cm ≥1.8 mm 010407 4 cm x 7 cm 0.4 mm–0.8 mm 012220 12 cm x 20 cm ≥1.8 mm 010312 3 cm x 12 cm 0.4 mm–0.8 mm 012620 16 cm x 20 cm ≥1.8 mm 010412 4 cm x 12 cm 0.4 mm–0.8 mm 012202 20 cm x 20 cm ≥1.8 mm Thick 012124 12 cm x 24 cm ≥1.8 mm 011101 1 cm x 1 cm 0.8 mm–1.7 mm 012225 20 cm x 25 cm ≥1.8 mm 011102 1 cm x 2 cm 0.8 mm–1.7 mm Breast Kits–2 units from same donor, 011104 1 cm x 4 cm 0.8 mm–1.7 mm Thick 011204 2 cm x 4 cm 0.8 mm–1.7 mm 0B1612 6 cm x 12 cm 0.8 mm–1.7 mm 011307 3 cm x 7 cm 0.8 mm–1.7 mm 0B1416 4 cm x 16 cm 0.8 mm–1.7 mm 011407 4 cm x 7 cm 0.8 mm–1.7 mm 0B1616 6 cm x 16 cm 0.8 mm–1.7 mm 011510 5 cm x 10 cm 0.8 mm–1.7 mm 0B1816 8 cm x 16 cm 0.8 mm–1.7 mm 011312 3 cm x 12 cm 0.8 mm–1.7 mm 011412 4 cm x 12 cm 0.8 mm–1.7 mm Breast Kits–2 units from same donor, 011612 6 cm x 12 cm 0.8 mm–1.7 mm Ultra Thick 011416 4 cm x 16 cm 0.8 mm–1.7 mm 0B2612 6 cm x 12 cm ≥1.8 mm 011616 6 cm x 16 cm 0.8 mm–1.7 mm 0B2416 4 cm x 16 cm ≥1.8 mm 011816 8 cm x 16 cm 0.8 mm–1.7 mm 0B2616 6 cm x 16 cm ≥1.8 mm 011122 12 cm x 12 cm 0.8 mm–1.7 mm 0B2816 8 cm x 16 cm ≥1.8 mm 011016 10 cm x 16 cm 0.8 mm–1.7 mm 011216 12 cm x 16 cm 0.8 mm–1.7 mm 011206 6 cm x 20 cm 0.8 mm–1.7 mm 011208 8 cm x 20 cm 0.8 mm–1.7 mm 011220 12 cm x 20 cm 0.8 mm–1.7 mm 011620 16 cm x 20 cm 0.8 mm–1.7 mm 011202 20 cm x 20 cm 0.8 mm–1.7 mm 011124 12 cm x 24 cm 0.8 mm–1.7 mm 011225 20 cm x 25 cm 0.8 mm–1.7 mm

Synthes Available through Processed by Synthes CMF Musculoskeletal Transplant 1302 Wrights Lane East Foundation West Chester, PA 19380 125 May Street Telephone: (610) 719-5000 Edison, NJ 08837 To order call: (800) 522-9069 Telephone: (732) 661-0202 Fax: (877) 534-1560 Fax: (732) 661-2298 www.synthes.com

© 2006 Synthes, Inc. or its affiliates. DermaMatrix and Synthes are trademarks of Synthes, Inc. or its affiliates. MTF is a registered trademark Printed in U.S.A. 6/12 J7237-F of the Musculoskeletal Transplant Foundation. AlloDerm is a registered trademark of LifeCell Corporation.