Overview
Kensey Nash Corporation is able to produce bovine dermis derived collagen for use in a wide range of medical devices.Collagen is a natural protein and the predominant biomolecule found in blood vessels, dermis, tendons, ligaments, cartilage, and the organic phase of bone. Because of its many appealing characteristics, collagen has a long history of use in medical devices ranging from hemostats and surgical meshes to bone void fillers. The material is ideal because, when purified properly, it is extremely bio-friendly, can be provided in a variety of shapes and sizes, and acts as a temporary scaffold for tissue regeneration. Kensey Nash’s formulations of collagen are used in many medical devices including the Angio-SealTM Vascular Closure Device, which has been implanted in approximately 10 million patients worldwide since receiving PMA approval in 1996 and CE Mark approval in 2000.

Collagen Configurations:
• Open-celled Porous Sheets
• High-strength Sheets
• Putties
• Injectable Suspensions
• Highly Viscous Gels
• Three-dimensional Compression Resistant Shapes
• Coatings for Synthetic Structures
• Fibers
• Powders
• In Combination with Other Biomaterials

Potential End-Use Applications:
• Bone Graft Substitute
• Spinal Disc Repair
• Hemostatic Sponges and Powders
• Wound Dressings
• Cartilage Repair
• Surgical Mesh
• Vascular Graft Coatings
• Nerve Regeneration Conduits
• Tissue Augmentation and Support
• Dermal Contour
• Urinary Incontinence
• Drug Delivery
• Biopsy Marking

Collagen Formulations
Kensey Nash produces medical devices from various different collagen formulations. These materials are manufactured from purified collagen extracts from bovine dermis, which is a source of primarily Type I Collagen. The difference between Kensey Nash’s formulations is the degree to which the collagen fibers are dissociated. Collagen fibers are ordered bundles of collagen fibrils, which in-turn are ordered bundles of collagen molecules (tropocollagen). Kensey Nash is able to take advantage of this ultra structure to make medical devices with unique properties.

Fibrous Collagen is a unique material composed of collagen fibers. Mild processing techniques preserve the extensive aldol-type native cross-linking, which produces an insoluble, naturally fibrous collagen form. This collagen has a high degree of inherent mechanical strength, unmatched by other available collagen products on the market. Further, this collagen does not require chemical fixatives to maintain useful in-vivo or
in-vitro degradation profiles. It will persist in-vivo for several months without the
addition of chemical fixatives.

Fibrillar Collagen is another unique material preparation that is composed of collagen fibrils. This material is formed
by exposing collagen fibers to conditions that partially solubilize them, while maintaining a high order of fibrillar
architecture. The resulting product form has superior mechanical strength with an open porous structure. This collagen
will persist in-vivo for several weeks without the addition of chemical fixatives.

Soluble Collagen is a tropocollagen preparation extracted from young bovine dermis. Kensey Nash produces soluble
collagen so that the natural triple helical orientation of the collagen is maintained, and thus the biological properties
of this collagen are preserved. Kensey Nash’s manufacturing process removes the telopeptide region from the
material, rendering the preparation non-immunogenic. This collagen will persist in-vivo from hours to days without
the addition of chemical fixatives.

Our Fibrous Collagen Composite is a unique blend of Kensey Nash’s Fibrous and Soluble Collagens. The combination
of these two collagen formulations provides for optimum strength and handling characteristics. It can be made to have
an open porous structure that has been demonstrated to be conducive to infiltration, attachment, and proliferation of
a number of different cell types (e.g., fibroblasts, smooth muscle cells, endothelial cells, chondrocytes). This collagen
will persist in-vitro and in-vivo from several weeks to months without the addition of chemical fixatives.

Collagen Blending and Compounding
This capability is another technique employed by Kensey Nash to create unique biomaterials with customized
properties. These blends can be formed into solid sheets, three-dimensional shapes, putties, gels, or injectables. We
have experience with many different materials and forms including:

Calcium Minerals & Salts
• Calcium Phosphate
• Tricalcium Phosphate
• Hydroxyapatite
• Calcium Sulfate

Bioactive Glass

Natural & Synthetic Fibers

Nanoparticles

Synthetic Polymers
• Polylactides
• Polyglycolides
• PLA/PGA Co-Polymers

Polysaccharides
• Hyaluronic Acid
• Alginates

Biologics
• Demineralized Bone
• Growth Factors

Control of Mechanical Properties and Biodegradation
For applications where greater strength or longer in-vivo persistence is required, Kensey Nash has extensive experience in altering the physical and chemical properties of collagen. Cross-linking can be performed on any of the collagen formulations. Techniques include physical methods such as dehydrothermal cross-linking (DHT) that do not involve the addition of chemicals, and chemical methods such as using carbodiimides or aldehydes. Additionally, Kensey Nash has other proprietary methods for orienting the fibers in the collagen to impart greater strength. Kensey Nash can optimize these methods of formulation to provide the best material properties for your application.

Safety
With twenty years of experience developing bovine-derived collagen based medical products, Kensey Nash has been on the forefront of implementing strategies to eliminate risks that might be associated with the medical use of animal derived biomaterials. Our collagen formulations are treated to render the collagen non-immunogenic and highly biocompatible. Kensey Nash’s manufacturing processes also include validated viral inactivation steps. The safety of our collagen has been demonstrated in numerous animal and human clinical studies. In support of successful product approvals and clearances, Kensey Nash maintains, with the FDA and several EU Notified Bodies, Device Master Files for its collagen products.

Closed Herd
The use of animal-derived materials in the manufacturing of medical devices has come under increased regulatory scrutiny related to the bovine form of a transmissible spongiform encephalopathy (otherwise known as BSE or “mad cow disease”). Kensey Nash has taken precautions to assure that our collagen is safe for human use and meets all applicable U.S. and European regulations. As an additional level of safety, we use sourcing controls that meet the EN 12442-2 definition of a Closed Herd. This means that Kensey Nash has full breeding history for the animals traceable to birth, documentation that new animals are introduced only from other closed herds, feeding history certifying that the animals have not been fed mammalian protein in their lifespan, and controls in place at the tissue handling facilities to minimize the risk of cross-contamination.

EDQM Certification
Kensey Nash has received the European Directorate for the Quality of Medicines (EDQM) Certificate of Suitability, attesting to the compliance for bovine collagen sourcing, processing and manufacturing controls. Kensey Nash’s bovine collagen is derived from the dermis, which is classified as a Category C Tissue with no detectable infectivity by the World Organization for Animal Health (OIE). There are no documented cases of prions, the abnormal protein associated with BSE, in Category C Tissue such as dermis.

Manufacturing Controls
In addition to taking measures to ensure that the starting materials are disease free, Kensey Nash has controls in place to ensure that the materials remain safe throughout various manufacturing processes. Our manufacturing facility is ISO 13485 certified and our collagen is processed in certified ISO Class 8 cleanrooms. Kensey Nash’s trained manufacturing staff has extensive experience in working with our collagen, and each collagen process has undergone rigorous process validation. Additionally, collagen materials regularly undergo stringent Quality Assurance biochemical and biomechanical testing to ensure that the material always meets governmental and customer specifications.