Bovine Collagen (Zyderm, Zyderm II, Zyplast)

Bovine collagen is collagen derived from cows. It is available in several forms, and can be used for superficial or deep wrinkles and depressions, and for lip augmentation. Commercially available bovine collagen fillers are 95% Type I and 5% Type III collagen. The product contains 0.3% lidocaine, a topical anesthetic. Products are available as 0.5-1.5 ml preloaded syringes. It is usually injected with a 30-33 gauge, 1/2" needle.

What bovine collagen dermal fillers are available?

Zyderm I is a 35 mg/ml suspension of bovine collagen. It is injected into the superficial dermis with the needle at a 20-30 degree angle to the skin. Proper placement will result in a yellow blanching of skin. Zyderm I is generally used to correct fine lines (e.g. perioral or periocular). It is the most forgiving of the three available bovine collagen preparations. As it loses water rapidly, overcorrection to 1.5-2.0X is common practice.

Zyderm II is a 65 mg/dl suspension of bovine collagen. It is more viscous than Zyderm I. It is injected into upper dermis; if it is placed too superficially, persistent whiteness can result. It is used for more substantial defects (e.g. shallow scars). It is usually placed with an overcorrection of up to 1.5X.

Zyplast is 35 mg/ml suspension of bovine collagen cross-linked with 0.0075% gluteraldehyde. Due to the cross-linking, it is longer lasting than Zyderm II. It is also less immunogenic. It is injected into the reticular dermis at an angle to the skin of 45-90 degrees. It does not cause immediate blanching, but rather a delayed blanch. It is suitable for deep wrinkles (e.g. deep nasolabial folds, marionette lines) and lip augmentation It is contraindicated in the glabellar area due to risk of vascular occlusion with deep injection. No overcorrection is recommended.

Is skin testing required with use of bovine collagen?

There is potential for allergic reactions to bovine collagen, with a 5.5%-6.5% sensitivity rate reported. 2.5%-3.5% of tested people respond to a single test, and approximately 3.1-3.6% of those negative on single testing were positive on repeat testing. Skin testing is therefore required prior to use of a bovine collagen dermal filler.

How is skin testing performed?

0.1 ml of Zyderm I is injected subcutaneously (e.g. in forearm). A positive reaction is swelling, induration, tenderness or erythema that persists or occurs more than 6 hours after injection. It is common practice to do a second skin test two weeks after the first and to monitor for an additional two weeks. Positive reaction on either test is a contraindication to bovine collage use. A negative test allows treatment four weeks after the first test or two weeks after the second test. A single retest with two weeks of observation is suggested in people getting retreated with bovine collagen.

For all skin tests, the test site should be examined 48-72 hours post-placement and then again at 2-4 weeks. Positive reactions (erythema, induration) can last 4-6 months, and in some cases up to 2 years. Serum sickness-type reactions have been documented.

How should bovine collagen allergy be treated?

Allergy to bovine collagen can be treated with topical or oral corticosteroids, or tacrolimus ointment.

Does bovine ollagen work to improve the appearance of wrinkles?

According to the FDA, in the pivotal study for Restylane, 138 patients were injected with Restylane, a hyaluronic acid filler, in the naso-labial fold on one side of the face and Zyplast on the other. At “baseline”, defined as the point at which optimal correction had been sustained for two weeks, Restylane resulted in an improvement from 3.29 to 1.80 on the 5 point Wrinkle Severity Rating Scale (SRS) as compared to 3.31 to 1.79 for Zyplast. At six month follow-up, the effects of the two treatments were comparable; the SRS scores were 2.36 for Restylane and 2.94 for Zyplast (a difference of less than one point was not considered to be clinically meaningful.)

How long does bovine collagen last to reduce the appearance of wrinkles?

The duration of effect is approximately 3-9 months. It lasts longest in areas of least motion. A decreased response to repeat injections has been reported.

What side-effects occur with use of bovine collagen?

Hypersensitivity reactions can occur about two weeks after treatment, presenting as swollen, indurated granulomas. These resolve spontaneously without scarring, but can persist for up to a year. They are treated with NSAIDS and intralesional triamcinolone. Sterile abscesses occur in 1-4/10,000 treatments. It presents as a sudden onset of pain days to weeks after injection; this is followed by tense edema, erythema, and fluctuant nodules. Scarring can result. It is treated with drainage, intralesional steroids, and oral antibiotics. Other complications include: ecchymosis, too superficial placement with beading, and too deep placement with intravascular occlusion. The latter presents as an immediate cutaneous blanch accompanied by pain. It should be treated with warm compresses and topical nitroglycerine for vasodilation.

Who should not use bovine collagen?

Bovine collagen is contraindicated in people with allergies to collagen or lidocaine; severe or multiple allergies; planning desensitization to meat products; or taking immunosuppressive medications. Caution is recommended in those with: keloids; active infections; atopy; autoimmune disease; bleeding disorders; or taking aspirin or NSAIDs

How is it stored?

Bovine collagen products have a six month shelf life. Refrigeration (4° C) is required.

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