XCM Biologic Tissue Matrix. Regenerative matrix for reinforcement and repair of soft tissue. Hydrated, ready-to-use Allows for cellular infiltration Strength without crosslinking
XCM Biologic Tissue Matrix XCM Biologic Tissue Matrix is a sterile non-cross-linked 3-D matrix derived from porcine dermis. Dermis is composed of cells and extracellular matrix (ECM), a combination of proteins, proteoglycans, glycosaminoglycans, and other biological materials produced by cells that form the structures of all the tissues in the body. XCM Biologic Tissue Matrix is manufactured by Kensey Nash Corporation and available through Synthes CMF. XCM Biologic Tissue Matrix undergoes Kensey Nash s proprietary Optrix process, which has been developed to be strong enough to disinfect the tissue, inactivate viruses, and remove the cells, yet gentle enough to maintain the bulk of the natural ECM components and minimize damage to the tissue architecture. The result is a strong biologic implant with the properties needed to facilitate soft tissue healing. XCM Biologic Tissue Matrix is ready-to-use, right out of the package. No hydrating or rinsing is required. Once the tissue matrix is implanted, it provides a structure that can be infiltrated by the body s cells. SEM cross section of XCM Biologic Tissue Matrix (500 magnification) Synthes 1
Features XCM Biologic Tissue Matrix provides reinforcement and repair of soft tissue during healing. Hydrated and ready-to-use out of the package Structurally allows for cellular infiltration Strength without crosslinking Can be stored at room temperature No risk of human disease transmission No prestretching required Large sizes available Consistent thickness No orientation required Terminally sterilized Hyaluronan Collagen Elastin Glycoprotein 2 Synthes XCM Biologic Tissue Matrix
Fibroblasts growing into XCM Biologic Tissue Matrix after 7 days in culture. Immunohistochemical staining of intracellular actin filaments (red) and nuclei (blue) show excellent attachment (200 magnification) + Proteoglycan Molecule Clinical applications Clinical applications include, but are not limited to the following: Hernia repair Defects of the thoracic wall Suture line reinforcement Muscle flap reinforcement Plastic and reconstructive procedures Breast reconstruction Abdominal wall reconstruction Orofacial reconstructive procedures + Immunohistochemical stains courtesy of Vacanti Laboratory for Tissue Engineering and Organ Fabrication, Massachusetts General Hospital Synthes 3
Indications and Contraindications Indications XCM Biologic Tissue Matrix is indicated for use in general surgical procedures for the reinforcement and repair of soft tissue where weakness exists including, but not limited to; defects of the thoracic wall, suture line reinforcement, and muscle flap reinforcement; hernia repair; soft tissue reconstructive procedures including but not limited to plastic and reconstructive surgical applications such as breast reconstruction, abdominal wall reconstruction, and orofacial reconstructive procedures; and for reinforcement of the soft tissues, which are repaired by suture or suture anchors. XCM Biologic Tissue Matrix is intended for one time use. Contraindications This device is derived from a porcine source and should not be used for patients with known sensitivity to porcine material. The device is contraindicated for patients known to be undergoing desensitization injections to meat products, as these injections can contain porcine collagen. Abdominal wall XCM Biologic Tissue Matrix placement options for abdominal wall reconstruction and hernia repair. A B C D E A Onlay B Inlay C Sublay D Underlay E Intraperitoneal 4 Synthes XCM Biologic Tissue Matrix
Device Properties Biomechanical Testing XCM Biologic Tissue Matrix has been subjected to biomechanical testing to characterize its physical properties. Tensile testing was conducted according to internationally recognized standard procedures, which subjects a dogboneshaped sample to tensile forces at 50 mm per minute and measures the maximum tensile force.* All forces are normalized to the width of the dogbone. XCM Biologic Tissue Matrix demonstrates an average tensile strength of 130 N/cm, greater than leading products made from PTFE, heavyweight macroporous polypropylene, and midweight macroporous prolene/cellulose/pds, and well in excess of normal human fascia. 1 N/cm 140 120 100 80 60 40 20 0 60 XCM Biologic Matrix Tensile strength Native Fascia strength=16 N/cm Composite Prolene/PDS P-propylene Suture pull-out strength PTFE Testing was conducted to determine the ability of the tissue matrix to withstand suture pull-out forces. A #2 suture was placed 2 mm from the edge of the device. XCM Biologic Tissue Matrix demonstrates a suture retention strength of 54 N, far in excess of PTFE and midweight macroporous prolene/cellulose/pds. N 50 40 30 20 10 0 XCM Biologic Matrix Composite Prolene/PDS PTFE * Data on file at Kensey Nash Corporation Synthes 5
Kensey Nash Corporation s Optrix Cleansing Process Kensey Nash is a regenerative medicine company with more than 20 years of experience in processing biologic materials. Kensey Nash has drawn from this experience to develop the Optrix cleansing process. This tissue cleansing process removes antigenic components from biologic materials while maintaining the native collagen structure and key extracellular matrix molecules used in tissue reconstruction. 2 The result is a strong, acellular biologic graft that facilitates soft tissue healing.* Key features of the Optrix process used in the manufacturing of XCM Biologic Tissue Matrix include:* Removal of cells and DNA Inactivation and clearance of viruses Maintenance of intact collagen structure for excellent strength and durability without crosslinking Preservation of natural fibrous architecture that provides a scaffold for cell in-growth and proliferation Retention of beneficial extracellular matrix molecules resulting in a scaffold that allows revascularization and tissue regeneration Hematoxylin and eosin image of XCM Biologic Tissue Matrix (bottom). Note cells (dark blue) in raw material (top), and no cells and preservation of natural architecture in XCM Biologic Tissue Matrix. 1200 DNA Measured by Pico Green 1000 ng DNA/mg 800 600 400 200 0 Raw Dermis XCM Biologic Matrix Porcine SiS Device Human Dermis Device * Data on file at Kensey Nash Corporation Results of Pico Green testing measuring the amount of DNA in a test sample. XCM Biologic tissue matrix is reduced to background levels of residual DNA. 6 Synthes XCM Biologic Tissue Matrix
Histological Profiles Immunohistochemical evaluation of XCM Biologic Tissue Matrix confirms that the major components of the extracellular matrix are preserved after processing. + XCM Biologic Tissue Matrix was evaluated for proteins such as collagen. Collagen is the most abundant structural protein found in mammals and plays an important role in tissue organization and biomechanical support. 3 Utilizing immunohistochemical assays, various collagen types have been confirmed to be present in XCM Biologic Tissue Matrix including types 1, 3, 4 and 7 collagen.* + Types 1 and 3 collagens are produced by fibroblasts and are the essential structural elements of most soft tissues. 4 Types 4 and 7 collagens provide attachment sites for epithelial, endothelial, and mesothelial cells. 2 Maintenance of the natural collagen architecture as demonstrated in the XCM Biologic Tissue Matrix is an important property of tissue regeneration scaffolds. 5 The presence of elastin was confirmed through Van Gieson staining. 2 Elastin is another important structural protein required for proper biomechanical function of various soft tissues. 6 As elastin is degraded, its fragments become matrikines which are chemotactic for numerous cell types. 7 Immunohistochemical staining in raw dermis (top) and XCM Biologic Tissue Matrix (bottom). Purple staining indicates cells and red staining indicates the presence of hyaluronic acid. + * Data on file at Kensey Nash Corporation + Immunohistochemical stains courtesy of Vacanti Laboratory for Tissue Engineering and Organ Fabrication, Massachusetts General Hospital Synthes 7
Histological Profiles Immunohistochemistry was used to confirm the presence of glycoproteins such as fibronectin and laminin. +2 Fibronectin plays a vital role in cell adhesion, cell differentiation, and is highly involved in tissue reconstruction. 8 Laminin is an important molecule for the adhesion of epithelial, endothelial, and mesothelial cells, and a key factor in tissue maintenance. 9 Alcian blue staining and spectrophotometric analysis by Blyscan assay confirmed the presence of sulfated glycosaminoglycans (GAG). Immunohistochemistry confirmed the presence of non-sulfated GAGs (hyaluronic acid). + * GAGs are highly charged molecules that are important for cell-cell signaling and cell-matrix interaction. GAGs sequester water for structural support and play important roles in the regulation of many tissue functions, such as tissue repair. 10 Immunohistochemical staining in raw dermis (top) and XCM Biologic Tissue Matrix (bottom). Blue staining indicates cells and green staining indicates fibronectin. + * Data on file at Kensey Nash Corporation + Immunohistochemical stains courtesy of Vacanti Laboratory for Tissue Engineering and Organ Fabrication, Massachusetts General Hospital 8 Synthes XCM Biologic Tissue Matrix
Sheep Fascia Repair Study A 4 4 cm window defect was created in sheep fascia lata and abdominal wall fascia and repaired with XCM Biologic Tissue Matrix. After 6 and 12 weeks, the implant sites were harvested and subjected to mechanical testing and histological analysis. The implant sites appeared to be well integrated with the surrounding tissue at both 6 and 12 weeks. There was no evidence of bulging of the underlying muscle. Based on tactile feel, the repaired tissue felt identical to the native host tissue.* Sheep fascia window defect at the time of surgery (left) and repaired with XCM Biologic Tissue Matrix (right). The tissue matrix was fixed upon explantation, sectioned, and stained by hematoxylin and eosin to assess cell penetration and tissue repair. Histology showed excellent incorporation with the surrounding tissues and cell infiltration.* Surgical site after 6 weeks (left) and 12 weeks (right). * Data on file at Kensey Nash Corporation Synthes 9
Sheep Fascia Repair Study Biomechanical testing was conducted by cutting dogbone-shaped samples from the repaired tissue at the center of the implant. The test samples were subjected to tensile testing at 24 mm per minute. The biomechanical testing proved that the repair sites implanted with XCM Biologic Tissue Matrix maintained strengths greater than normal fascia throughout the healing process.* Histology at 6 weeks (left) and 12 weeks (right). Note cell infiltration at 6 weeks, and repair tissue at 12 weeks. 150 Surgical Site Strength over Time Tensile Strength (N/cm) 120 90 60 30 0 Initial 6 week 12 week XCM Biologic Tissue Matrix Healing Fascia Baseline Fascia Biomechanical testing of surgical sites after healing. XCM Biologic Tissue Matrix maintains strengths greater than native tissue throughout the healing process. * Data on file at Kensey Nash Corporation 10 Synthes XCM Biologic Tissue Matrix
Product Information XCM Biologic Tissue Matrix, sterile, hydrated Dimensions XM106.0204S 2 cm 4 cm, thick XM106.0407S 4 cm 7 cm, thick XM106.0416S XM106.0516S XM106.0612S XM106.0616S XM106.0620S XM106.0812S XM106.0816S XM106.0820S XM106.1016S XM106.1020S XM106.1220S XM106.1620S XM106.1625S XM106.2020S XM106.2025S XM106.2030S 4 cm 16 cm, thick 5 cm 16 cm, thick 6 cm 12 cm, thick 6 cm 16 cm, thick 6 cm 20 cm, thick 8 cm 12 cm, thick 8 cm 16 cm, thick 8 cm 20 cm, thick 10 cm 16 cm, thick 10 cm 20 cm, thick 12 cm 20 cm, thick 16 cm 20 cm, thick 16 cm 25 cm, thick 20 cm 20 cm, thick 20 cm 25 cm, thick 20 cm 30 cm, thick Additional sizes may be available. Please contact your Synthes Sales Consultant for details. Note: For additional information, please refer to package insert. Synthes 11
References 1. U. Klinge, et. al. Modified mesh for hernia repair that is adapted to the physiology of the abdominal wall. European Journal of Surgery. 1998 Dec; 164(12): 951 960. 2. S.F. Badylak. The extracellular matrix as a scaffold for tissue reconstruction. Seminars in Cell & Developmental Biology. 2002 Oct; 13(5): 377 383. 3. W. Friess. Collagen biomaterial for drug delivery. Eur J Pharm Biopharm. 1998 Mar; 45(2): 113-136. 4. M.J. Beckman, et. al. Collagen. Encyclopedia of Biomaterials and Biomedical Engineering, 2004: 324 334. 5. M. Sandor, et. al. Host response to implanted porcinederived biologic materials in a primate model of abdominal wall repair. Tissue Engineering: Part A 14(12), 2008: 2021 2031. 6. L. Debelle, A.M. Tamburro, Elastin: molecular description and function. International Journal of Biochemistry & Cell Biology 31(2), 1999: 261 272. 7. L. Duca, et. al. Elastin as a matrikine. Critical Reviews in Oncology/Hematology. 2004 Mar; 49(3): 235 244. 8. R.A. Brown, J.B. Phillips. Cell Responses to Biomimetic Protein Scaffolds Used in Tissue Repair and Engineering. International Review of Cytology 262, 2007: 75 150. 9. J. Tzu, M.P. Marinkovich. Bridging structure with function: structural, regulatory, and developmental role of laminins. International Journal of Biochemistry & Cell Biology 40(2), 2008, 199 214. 10. D.D. Allison, K.J. Grande-Allen, Review. Hyaluronan: a powerful tissue engineering tool. Tissue Engineering. 2006 Aug; 12(8): 2131 2140. 12 Synthes XCM Biologic Tissue Matrix
Distributed by Manufactured by Kensey Nash Corporation 735 Pennsylvania Drive Exton, PA 19341 All technique guides are available as PDF files at www.synthes.com/lit Ö036.001.140öAB]ä 0086 036.001.140 AB 60100192 1/2011 Synthes, Inc. or its affiliates All rights reserved Synthes and XCM Biologic are trademarks of Synthes, Inc. or its affiliates