CYMETRA

Cymetra™ is a micronized form of AlloDerm® containing all the elements vital to replace tissue (collagens, elastin, and proteoglycans). However, because Cymetra™ has been micronized into small particles, Cymetra™ can be delivered as a minimally invasive tissue graft. Cymetra is a natural alternative to using the patient's own tissue or to traditional products that act as temporary substitutes for soft tissue. It gives patients a natural feel and appearance.

• Where Would You Like to Use Cymetra?
› Acne scar revisions / Depressed scar and other depressions
› Correction of Nasolabial and Melolabial Folds
› Perioral rhytids
› Lip reconstruction
› Marionette Complex and Malar Depression

• How Does Cymetra™ Work?
Cymetra is rehydrated with lidocaine, which not only prepares the syringe contents for injection, but also provides an anesthetic benefit for patient comfort. Once injected, Cymetra remodels just as AlloDerm® does.
The collagens and elastin in Cymetra provide structure for cell repopulation, and most importantly, preserved proteoglycans and proteins direct the patient's own cells to initiate revascularization and cell repopulation, integrating into the patient's own tissue. Because it is human tissue, Cymetra is metabolically compatible with patient's body, it will not elicit an inflammatory response nor graft rejection.

• Safety Profile
Cymetra™ is a particulated form of AlloDerm® acellular tissue. In more than 8 years and in more than 100,000 AlloDerm grafts, there has not been a single reported case of viral transmission with this material.
The safety of Cymetra is assured in the same way as that of AlloDerm. First, tissue banks thoroughly review donors' medical histories and extensively screen blood samples to ensure tissue is free of hepatitis B and C, HIV-I, HIV-II, HTLV-I, HTLV-II antibodies, and syphilis. In addition, LifeCell further examines donor history and tissue to minimize the potential for pathogenic contamination.
The tissue is put through a process that further enhances its safety. Solubilizing detergent washes inactivate HIV and further reduces the risk of transmission. The freeze-dried tissue is examined to determine that it is pathogen-free. It is then particulated and packaged aseptically in syringes ready for rehydration.

• Rehydration and Use Information
Cymetra is processed from donated human tissue supplied to LifeCell from contracted U.S. tissue banks utilizing the guidelines of the American Association of Tissue Banks. Using the proven, patented AlloDerm® Process, LifeCell processes the allograft tissue into a particulate acellular dermal matrix, first by removing the epidermis and the dermal cells, then by converting the dermal matrix into micronized particles through a process called cryo-fracture. Finally, the micronized particles are dried and placed in a syringe, allowing for extended shelf life and facilitating easy shipping and storage.
LifeCell's patented AlloDerm Process removes cells, which are targets for the immune response, without altering the collagen and extracellular matrix of the dermis. The resulting dermal matrix is immunologically inert and serves as a framework to support revascularization and cellular repopulation. This process facilitates engraftment of the dermal matrix into the patient's own tissue, resulting in natural tissue integration.

• How Supplied
Cymetra is supplied as a dried acellular particulate dermal matrix. The 330mg dried acellular dermal matrix is contained in a 5cc syringe. Cymetra is supplied only to licensed physicians or surgeons.
The 330mg reconstituted to a 1cc dosage form of Cymetra is for single-patient use only.

• Transport and Storage
Cymetra is transported at ambient temperature, then refrigerated upon receipt to maximize the shelf life. Although Cymetra is not shipped under refrigeration, this limited exposure to ambient temperature does not significantly affect the product efficacy or shelf life. The dispensing service or end user must maintain the tissue under appropriate storage conditions (1° -10° C or 34° -50° F). The expiration date for the particulate dermal matrix is recorded on the package label.

• Sterilization
Cymetra is produced under aseptic conditions (see Quality Assurance Section). LifeCell does not recommend sterilization of the tissue by the end-user. The sterilization process may result in structural damage and functional impairment of the tissue.

• Regulatory Status
AlloDerm is classified by the FDA as a human tissue for transplantation. It is the responsibility of the clinician to maintain recipient records for the purpose of tracking tissue post-implantation.

• Indication For Use
Under FDA regulation of human tissue for transplantation embodied in CFR Title 21 Part 1270, Cymetra is to be used in transplantation for the repair or replacement of damaged or inadequate integumental tissues.

• Contraindicitons
Use of Cymetra in patients exhibiting autoimmune connective tissue disease is not recommended. Cymetra is contraindicated in infected or nonvascular surgical sites, unless specifically prescribed by their physician.
Allograft tissue used to produce Cymetra is supplied in an antibiotic-supplemented medium. Therefore, Cymetra may contain trace amounts of the supplemented antibiotics. The specific antibiotics are listed on the packaging label. Cymetra should not be used in patients sensitized to those specific antibiotics.
Patients should avoid nonsteroidal anti-inflammatory drugs, including aspirin, for the two weeks preceding treatment with Cymetra.
Ancillary agents that may cause inflammation at the treatment site should be avoided.
Cymetra should not be used in periocular line correction or glabellar contouring.

• Procedure Notes
Cymetra should be used within two hours following rehydration.
If the needle should become clogged during injection, replace with a fresh needle.
Gentle massage of the treated area is recommended during and following the treatment. Some swelling and redness can be expected to occur following treatment. Excessive swelling and/or redness should be brought to the physician's attention.
Note:
Failure to follow the preparation instructions may lead to sub-optimal results.
1% Lidocaine not supplied with Cymetra.

• Preperation For Placement
Cymetra should be placed into a subcutaneous tissue plane. The matrix has been formulated to a consistency that will pass easily through a 26-gauge needle. Preparation of the injection site can be achieved using a variety of approaches to maximize patient comfort during and after the placement of tissue. If the injection site is susceptible to herpetic outbreak, the patient may be placed on prophylactic antiviral agents.
Topical anesthetics such and lidocaine/prilocaine cream can be used in the 20-30 minutes prior to the injection, especially if the site is particularly sensitive to needle puncture or subdermal increases in tissue volume, e.g. atrophic lip rehabilitation. Subcutaneous injection of local anesthetic, such as Xylocaine® (lidocaine Hcl) without Wydase® (hyaluronidase), have also been used at the injection site or as a nerve block to successfully prepare the site.
The rehydrated tissue graft contains 1.0% Xylocaine (lidocaine HCl) and local anesthesia at the injection site may be achieved within a few minutes of tissue placement. Placing ice on the site 2-3 minutes prior to injection has been reported to minimize patient discomfort until the intrinsic local anesthesia becomes effective.
If the area to be treated is extensive, surgeons may elect to administer a regional nerve block to allow for maximum manipulation and contouring of the tissue following the injection. This approach may also be used on patients who, in general, report high sensitivity to pain.

• Potential Problems During Postoperative Period
Because the Cymetra is placed in the subdermal or subcutaneous tissue plane, there is a potential for swelling, bruising, pain, or irritation during the immediate postoperative period. Skin redness and discoloration has been reported on rare occasions, however these should resolve within several weeks after the procedure. Lumpiness and nonuniformity of contour may occur if care is not taken to evenly distribute the material during the placement.
Cymetra is produced from human allograft skin that has been decellularized to remove cells that cause graft rejection or immunological reactions. However, as with any allograft tissue composed of proteins and proteoglycans, the graft may cause an allergic reaction or sensitivity. No allergic or immunological reactions have been reported in clinical studies involving up to 200 patients thus far.
No long-term studies have been conducted to evaluate the potential of Cymetra to cause cancer. Potential risks to an embryo or fetus are unknown at this time and there may be other risks or side effects that are also unknown at this time.

• Viral Inactivation
The AlloDerm Process includes a step in which donor tissue is incubated in a solution demonstrated to inactivate HIV-I ( >99.9% reduction of virus titer). However, this model cannot absolutely preclude the possibility of viral contamination of the processed human tissue with yet-to-be identified strains of HIV or guarantee that the tissue is absolutely virus-free. Therefore, Cymetra may transmit infectious agents.

• Potential Adverse Reactions
When used properly, Cymetra has been shown to support the migration and integration of host cells from the surrounding tissues. Conditions that could potentially inhibit the integration of Cymetra include:
• Low vascularity of the surrounding tissue
• Local or systemic infection
• Poor nutrition and/or poor general medical condition
• Specific or non specific immune response to some component of the product
• Certain antimicrobials/antiseptics

• Immune Response to Some Component of the Product
Hypersensitive, allergic or other immune response to Cymetra has not been seen in preclinical and clinical trials. Since Cymetra is composed of proteins, proteoglycans, and other components of human dermis, the potential does exist for such reactions.