Collagen injections: the first wrinkle fillers
Before hyaluronic acid, injectable collagen played a major role in wrinkle treatment.
Collagen is a structural protein naturally present in skin. It contributes to strength, firmness and extracellular matrix organisation. With ageing, production and renewal gradually decrease, contributing to lost skin density and wrinkles.
The idea of injecting collagen directly into skin was therefore logical: supplying a product to correct a depression or wrinkle immediately.
Bovine collagen was the first injectable filler approved by the FDA for aesthetic soft tissue correction. Zyderm was authorised in the United States in 1981. Other formulations followed, including Zyplast. For several years, these products were a reference in injectable filling.
They were mainly used for superficial wrinkles, folds and certain depressed scars.
Why did injectable bovine collagen pose an allergy problem?
The main disadvantage of bovine collagen was its animal origin.
Although its structure resembles human collagen, it is not identical. The immune system can therefore recognise certain proteins as foreign and trigger hypersensitivity.
Historical studies reported hypersensitivity reactions in a minority of patients. Delayed local reactions could notably involve redness, swelling, itching or induration.
To reduce this risk, a skin test was needed before treatment. Certain procedures even recommended two successive tests several weeks apart.
This was a major drawback: unlike an injection performed after medical assessment at a dedicated consultation, treatment had to be preceded by an allergy screening period.
However, a negative skin test could not completely exclude a later reaction.
The arrival of products with lower immunogenicity therefore considerably reduced bovine collagen's practical value.
Did collagen injections act for too short a time?
Result duration was their second weakness.
Once injected, collagen was gradually broken down by the body. Clinical duration varied between formulations, areas and studies, but older human or bovine collagen formulations generally provided correction lasting a few months.
The FDA currently gives an approximate duration of two to three months for pure animal- or human-derived collagen fillers.
This relatively short duration required repeated injections to maintain results.
For patients, this meant more sessions, higher cumulative cost and less lasting correction.
The development of hyaluronic acid gels fundamentally changed this situation: cross-linking slows breakdown and produces products adapted to very different indications.
Why did hyaluronic acid replace injectable collagen?
Hyaluronic acid had several characteristics particularly useful for facial injections.
It is a polysaccharide naturally present in the extracellular matrix. Its molecular structure is highly conserved between species, explaining its low immunogenic potential compared with bovine collagen.
Current products are generally obtained through bacterial fermentation, then modified, particularly through cross-linking, to control physical properties and tissue persistence.
However, benefits do not concern tolerance alone.
Different hyaluronic acid gels can have very different rheological properties. The doctor can therefore choose according to the objective: correcting a depression, restoring volume, projection, supporting a structure or improving certain skin characteristics.
This versatility accompanied a broader evolution in aesthetic medicine.
The aim is no longer simply “filling a wrinkle”. Modern facial ageing assessment considers skin changes, but also changes in fat compartments, supporting structures and facial volume.
A filler therefore needed to meet several anatomical and mechanical requirements. Hyaluronic acid proved far more versatile than older injectable collagens.
Did human collagen avoid allergies?
Human collagen products were subsequently developed to reduce bovine collagen's immunological problems.
CosmoDerm and CosmoPlast, for example, were approved in the United States in 2003. Their main advantage was no longer requiring the same prior allergy tests.
Yet this was not enough to reverse market developments.
At the same time, hyaluronic acid fillers were developing rapidly. They generally offered longer correction and a range of properties for more indications.
The problem with older collagen fillers was therefore not just allergy: even after reducing that risk, clinical value remained limited compared with new hyaluronic acid possibilities.
Were collagen injections dangerous?
Collagen injections were not abandoned solely because they were “dangerous”.
Bovine collagen products were used in many patients over several decades. They had recognised indications and could give good results when correctly used.
Nevertheless, they carried specific risks, particularly hypersensitivity reactions.
As with other injectable fillers, inflammatory or granulomatous complications could also occur. Filler injections also carry procedure-related risks independently of the product.
The move towards hyaluronic acid therefore reflects an improved balance of effectiveness, duration, versatility and constraints more than sudden abandonment of a technique considered dangerous.
Can collagen still be injected today?
Two often-confused concepts should be distinguished: injecting collagen as a filler and stimulating skin collagen production.
Older fillers directly containing bovine or human collagen have largely disappeared from routine aesthetic practice. For example, the FDA states that Zyderm's US approval was withdrawn in 2011.
However, collagen remains a major target of aesthetic treatments.
Many current techniques seek to stimulate fibroblast synthesis of new collagen rather than inject the protein directly.
This is a fundamental strategy change.
Injecting collagen and stimulating collagen synthesis: what is the difference?
Injecting collagen and stimulating its production rely on different mechanisms. Older collagen fillers directly supplied collagen to tissues to correct a wrinkle or depression. The effect was quickly visible, then gradually decreased as the body broke down the product.
Biostimulatory treatments do not supply collagen directly. They stimulate fibroblasts and gradually promote new collagen synthesis within tissues. This notably underlies certain injectable collagen stimulators. Other treatments, such as certain lasers or thermal energy devices, trigger tissue remodelling that may also promote new collagen formation.
Their action is therefore gradual: improvement appears over weeks or months as tissues remodel. A collagen-stimulating treatment should therefore not be confused with a collagen injection.
Which treatments now stimulate collagen production?
Several approaches may be offered according to the indication.
Injectable collagen stimulators, such as poly-L-lactic acid, gradually trigger a tissue response leading to new collagen formation. They are notably used when the aim is to improve certain volume losses and skin quality gradually.
Fractional lasers use another mechanism. They create microscopic ablation zones triggering skin repair and collagen remodelling.
Certain thermal energy technologies, particularly radiofrequency, also seek dermal remodelling and gradual extracellular matrix stimulation.
These treatments are not interchangeable. Choice depends on skin quality, age, area concerned, extent of sagging and desired result.
Hyaluronic acid or collagen stimulation: how should you choose?
The two approaches do not have exactly the same objective.
Hyaluronic acid particularly suits precise structural or volume correction. It can restore certain volumes, support an anatomical area (non-surgical lifting technique) or alter certain facial proportions.
A collagen stimulator instead follows gradual tissue stimulation. Results generally appear more slowly and depend on the patient's biological response.
In certain situations, the approaches can complement each other.
Localised volume loss should therefore not automatically lead to collagen synthesis stimulation, just as diffuse skin quality changes do not necessarily justify a filler injection.
Facial assessment determines what mainly involves volume loss, structural change, reduced skin quality or several mechanisms together.
Why is collagen being discussed so much again in aesthetic medicine?
The word “collagen” is now ubiquitous, but does not describe the same treatment as in the 1980s and 1990s.
At that time, collagen was mainly considered an injectable filler.
Today, the aim is more often to preserve, remodel or stimulate synthesis of collagen naturally present in tissues.
This reflects a different understanding of facial ageing. Rather than correcting each wrinkle separately, care may seek improved skin quality, restoration of certain structures and respect for natural facial proportions.
Collagen has therefore not disappeared from aesthetic medicine. How it is used has changed.
Why did older collagen fillers ultimately disappear?
Older collagen fillers combined several limitations: relatively short duration, frequent repeat treatments and, for bovine collagen, hypersensitivity risk requiring prior tests.
Meanwhile, hyaluronic acid provided a more versatile, weakly immunogenic and longer-lasting solution. Advances in gel formulation then created products with differing characteristics according to tissues and indications.
Collagen injections were therefore not abandoned because they were ineffective. They were mainly overtaken by technologies offering a better balance of safety, ease of use, precision and result duration.
In Geneva, treatment choice does not depend on product alone. Medical facial assessment identifies the origin of the observed change and determines whether it calls for a filler, collagen stimulation, skin treatment or combined techniques.
Article written by Dr Valeria Romano
Dr Valeria Romano supports each patient through a comprehensive approach to facial, body and intimate aesthetics, as well as skin and hair quality. Every treatment is based on a personalised medical assessment.
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