Collagen injections and your skin

With time, skin starts to lose volume and elasticity causing natural or accelerated signs of ageing. Over the last 2 decades several kinds of dermal filler/dermal injectables have been developed to help provide a solution to prematurely ageing skin.  Collagen was one of the very first facial fillers to be tested and approved for facial augmentation, posing an appealing treatment for the signs of ageing due to collagen being a pre-existing and natural component of human skin.

What is collagen?

Collagen is an essential protein required to maintain the integrity of human skin. Vitamin C is known to be vital for healthy collagen formation as vitamin C deficiency (scurvy) causes skin tissues to disintegrate. When collagen levels are high and collagen integrity is healthy, skin can be voluminous, plump and resistant to skin creasing. When collagen levels are low and/or collagen integrity is unhealthy, skin can lax, encouraging the formation of jowls, sagging, fine lines and wrinkles.

Collagen proteins work similarly to scaffolding, allowing skin and soft tissues to uniformly sit on top of a person’s bone structure. There are at least 16 different types of collagen; however, the majority of collagen found in the human body is type I, II or III1.

Collagen levels naturally decline with age. Interestingly exposure to sunlight without sunscreen can stimulate collagen levels, however while also stimulating the release of collagen degrading enzymes known as matrix metalloproteinases2 Both naturally aged and photo-aged skin show an overall decline in collagen levels plus a change in the health of collagen i.e. hardening.

Do collagen injections really work?

While native collagen in partnership with flexible elastin fibres and plumping hyaluronic acid polymers forms a smooth skin structure, injected collagen works differently. Collagen injections work to fill and plump skin because when collagen is warmed to body temperature it turns from a solution into a gel. This means collagen can be injected as a flowing liquid able to fill areas of sagging skin before becoming an implantable filler or implant3 Rather than replace existing collagen structures inside of skin, collagen injections fill these spaces independently.

Collagen injections are therefore helpful for;

  • Smile lines
  • Frown lines
  • Crow’s feet
  • To create fuller lips i.e. as lip implants
  • For resolution of acne scars i.e. depressed or toothpick scars
  • Depressed scars not caused by acne
  • Viral pock marks
  • Nasolabial lines and folds
  • Fine lines and wrinkles
  • Injection rhinoplasty

Note: Collagen injections are most effective in the temporary resolution of mild to moderate signs of ageing. Collagen injections are not considered a complete solution for moderate to severe signs of ageing, however in these instances may be used in combination with other therapies such as Botox, peels and laser resurfacing.

Whether collagen injections will work to resolve a patients signs of ageing, depends on appropriate treatment selection. Collagen injections work intradermally i.e. within skin layers, they are therefore most effective for the first signs of ageing which have only an intradermal cause. Deeper wrinkles often have a dermal cause, a muscular cause and a subcutaneous cause. Therefore collagen injections alone are unlikely to create a patients desired end result and must therefore be used in combination with other treatments able to resolve the muscular and subcutaneous cause i.e. Botox4.

Types of collagen injection

There are many different brands of collagen filler available today however there are only 2 kinds of collagen used under any brand name. This will be either bovine collagen i.e. cow derived or human collagen.

In 2001 the single most popular substance for soft-tissue augmentation was injectable bovine collagen. Collagen injections using bovine collagen are usually lower in cost than human collagen, however may not last as long. Bovine collagen injections were the first to be clinically tested as a face filler in the 1970s on patients who had depressed acne scars, subcutaneous atrophy, wrinkling, viral pock marks and other contour defects. The results showed a 50 to 85% improvement which was sustained for 3 to 18 months5.

Following these trial results, a new collagen filler was commercialised under the name Zyderm Collagen. Receiving full FDA approval in July 1981, this was the first time in history that an injectable agent had been FDA approved for soft tissue augmentation.

Zyderm collagen fillers/implants are made from 95-98% type I collagen with the remaining percent being type III collagen6. Normal dermal collagen is averagely 80% type I collagen and 20% type III collagen. Therefore bovine collagen injections not only use a skin-similar active, they also use this active to a skin-similar ratio.

Collagen is naturally degraded over time and the same dermal processes which degrade native collagen will also with time degrade injected collagen. The makers of Zyderm now also manufacture a collagen injection known as Zyplast Collagen Implant which uses a small amount of cross-linking agent to essentially prolong the lifetime of the injectable. A cross-link is a type of chemical bond, therefore Zyplast Collagen Implant fillers are not just hardened by body temperature, but also bonded together to help prolong collagen filler results. Specifically cross linkage of collagen injectables enables the filler to resist proteolytic degradation7 – a natural form of collagen degradation.

Collagen injections derived from human collagen may come from 2 sources, they may either be taken from deceased donor patients or may be grown in a laboratory by collagen fibres taken from another site on the same individual.

Human collagen injections have been commercialised under the below brand names;

  • Autologen – prepared from a patient’s own tissue
  • Isologen – as above
  • Dermalogen – prepared from human collagen donors

Human collagen injections may last longer as they’re not solely an injection of collagen but often a mixture of collagen and other matrix proteins such as elastin. Dermalogen injections are also associated with new vessel formation and have been seen to stimulate the patient’s own production of collagen.

Note: Human collagen injections are an alternative for patients with allergy risk to bovine collagen.

Collagen injections for acne scars

Skin’s healing process involves local amplification of specific types of collagen, when skin either creates too much collagen or not enough collagen, surface irregularities may occur. This is common with healing of acne lesions which often result in scar types known as;

  • Ice-pick scars
  • Rolling scars
  • Boxcar scars
  • Atrophic scars
  • Hypertrophic/keloid scars

Note: All of the above acne scar types result in a depression or lump. Collagen injections are suitable for depressed scars with best results seen in the treatment of atrophic and rolling scars.

Skincare can to a degree help control acne scarring. For example inflammation is stronger in patents with acne scars than those without, in general an increased length and duration of inflammation is linked with an increased risk of developing acne scarring. This therefore means anti-inflammatory skincare may help reduce acne scar risk. However If a person has a skin type which is prone to acne scarring, anti-inflammatory skincare will very rarely prevent acne scarring.

80-90% of patients with acne scars experience scars associated with a loss of collagen i.e. atrophic scars8 . A study published by the Canadian Society of Plastic Surgeons tested the efficacy of a collagen injection known as Artecoll against depressed acne scars. The study concluded 95.8% of patients noted significant subjective improvements after the injection, with the majority of patients noting these effects with just one injection9.

Collagen injections vs. Botox

Although both collagen injections and Botox may be used to help alleviate fine lines and wrinkles, collagen injections have a completely different mode of action to Botox injections. Collagen injections are injectable fillers or implants which act to plump skin by residing underneath the skins surface. Botox injections inhibit muscular movement therefore stopping the creation of dynamic fine lines and wrinkles i.e. when a person frowns. Collagen injections work to resolve dermal causes of wrinkles. Botox injections work to resolve muscular causes of wrinkles.

For these differences Botox injections are very effective at resolving ageing changes to the upper face i.e. areas prone to dynamic wrinkling such as the forehead. While collagen injections can also be helpful for the upper face, they also work well in the lower face.

Moderate signs of ageing may be effectively treated with a combination of collagen injections and Botox to A) treat dermal causes of ageing and B) treat muscular causes of ageing.

Collagen injections side effects

Up to 3.5% of patients who undergo testing for bovine collagen compatibility are allergic, with 70% of these reactions being visible in 48-72 hours10. Allergenicity testing is recommended before any kind of bovine collagen injection. So called double testing for bovine collagen sensitivity may also be recommended for caution. Signs of collagen injection side effects include swelling, inflammation, tenderness or erythema which persists for 6 hours or longer after the collagen injection.

Pros and cons of collagen injections

The greatest con of collagen injections is also their greatest pro. Collagen injections are temporary fillers and therefore subsequent treatments will be needed to maintain the same end result. This may be seen as a con, but can also be seen as a pro for patients worried about the final result or the look of ‘being done’.

Note: Bovine collagen injections are thought of as the most temporary form of collagen filler with human collagen injections lasting longer. Conversely bovine collagen injections are significantly cheaper than human collagen injections.

Depending on the physician 1, 2 or 3 collagen injections may be required to reach end results. Published texts infer desired results can be achieved with 1 collagen injection if the necessary amount of filler is used[11]. The end result is greatly influenced by a physician’s skill of injection therefore it’s important to choose an aesthetics clinic cautiously.

How long do collagen injections last?

The minimum amount of time a collagen injection should last is 2 to 4 months, which, depending on the type of collagen injection used may require from 1 to 4 injections12 . Collagen injection studies conclude 30% of patients report collagen injection results to last for 18 months whereas the remaining 70% require touch up treatments at intervals of 3 to 12 months.

Noticeably the most long lasting collagen injection results appear in the treatment of glabellar frown lines (the area between the eyebrows and forehead) and acne scars. Collagen injections ‘wear-off’ when the implanted collagen is displaced from the dermis into the subcutaneous space13 .

Can you use filler for forehead lines?

Two types of wrinkles are responsible for forehead lines, the first are known as dynamic wrinkles caused by the continual movement/expression of facial muscles. The second type of wrinkles are known as static wrinkles and are present even when facial muscles are not active. Static wrinkles may be lessened by Botox, however may only be cosmetically resolved with the use of other injectables which smooth and plump skin i.e. collagen injections. Forehead lines may resolve quickly after a filler injection, however will need subsequent injections to retain the same effect.

Collagen vs. hyaluronic fillers

Collagen injections were once the go-to for soft tissue facial augmentation however the development of hyaluronic acid fillers has seen their popularity wane. Hyaluronic acid fillers have a much lower risk of side effects or reaction while also being more cost effective and longer lasting. Hyaluronic acid fillers will last from between an average of 3 to 6 months, with specific hyaluronic acid fillers such as Juvederm lasting for an average minimum of 6 months14 . Hyaluronic acid used in hyaluronic acid filers is identical to the hyaluronic acid found naturally inside of skin.

Note: If considering collagen injections for facial rejuvenation a consultation should be completed to determine the most appropriate type of filler for the patient and treatment area in question. Factors to take into consideration include risk of allergy, age, depth of textural irregularity and size of treatment area.

Sources and references
  1. Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 22.3, Collagen: The Fibrous Proteins of the Matrix. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21582/

  2. Modulation of skin collagen metabolism in aged and photoaged human skin in vivo.

  3. H. Chung, J. Y. Seo, H. R. Choi, M. K. Lee, C. S. Youn, G. Rhie, K. H. Cho, K. H. Kim, K. C. Park, H. C. Eun

    4. J Invest Dermatol. 2001 Nov; 117(5): 1218–1224. doi: 10.1046/j.0022-202x.2001.01544.x

  4. Skin filling. Collagen and other injectables of the skin. A. W. Klein, Dermatol Clin. 2001 Jul; 19(3): 491-508, ix.

  5. Skin filling. Collagen and other injectables of the skin. A. W. Klein, Dermatol Clin. 2001 Jul; 19(3): 491-508, ix.

  7. Knapp TR, Kaplan EN, Daniels JR Injectable collagen for soft tissue augmentation. Plast Reconstr Surg

    60:389, 1977

  8. Wallace DG, McPherson JJ, Ellingsworth LE, et al: Injectable collagen for tissue augmentation. In Nimni

    ME (ed): Collagen, Vol. I11 Biotechnology. Boca Ratan, CRC Press, Inc., 1988, pp 117-144

  9. Skin filling. Collagen and other injectables of the skin. A. W. Klein, Dermatol Clin. 2001 Jul; 19(3): 491-508, ix.

  10. Acne Scars: Pathogenesis, Classification and Treatment, Gabriella Fabbrocini, M. C. Annunziata, V. D’Arco, V. De Vita, G. Lodi, M. C. Mauriello, F. Pastore, G. Monfrecola, Dermatol Res Pract. 2010; 2010: 893080. Published online 2010 Oct 14. doi: 10.1155/2010/893080

  11. Solomon P, Sklar M, Zener R. Facial soft tissue augmentation with Artecoll®: A review of eight years of clinical experience in 153 patients. The Canadian Journal of Plastic Surgery. 2012;20(1):28-32.

  12. Skin filling. Collagen and other injectables of the skin. A. W. Klein, Dermatol Clin. 2001 Jul; 19(3): 491-508, ix.

  13. Klein AW Indications and implantation techniques for the various formulations of injectable collagen. J

    Dermatol Surg Oncol 14(Suppl 1):49, 1988

  14. Assessing nonsurgical options for facial restoration. Hamilton TK. Dermatol Ther. 2007 Mar;20 Suppl 1:S5-9. Review.

  15. Stegman SJ, Chus S, Bensch K, Armstrong R A light and electron microscopic evaluation of Zyderm, Collagen,

    and Zyplast Implants in aging human facial skin: A pilot study. Arch Dermatol 123:1644, 1987

  16. Assessing nonsurgical options for facial restoration. Hamilton TK. Dermatol Ther. 2007 Mar;20 Suppl 1:S5-9. Review.