Special Feature: Rejuvenating the Face with Collagen-Stimulating Injectables

By Ellie Holden / 02 Aug 2023

Aesthetics explores the rise of collagen stimulators and the benefits for practitioners to implement them in-clinic

Collagen-stimulating products have been rising in popularity over the last few years. With increased interest and a growing portfolio of products emerging, it is expected that these injectables will have an estimated revenue growth of 12% a year for the next five years.1 This raises the question as to whether practitioners should begin, or focus more on, implementing them into their practices.

Outside of business opportunities, there are multiple reasons why collagen stimulators are gaining more attention. According to aesthetic practitioner Dr Munir Somji, patients are searching for long-lasting effects from treatments. Dr Somji has noticed a rise in patients requesting the treatment and believes there are several reasons why they are gaining more attention. 

He notes, “Collagen stimulators tend to provide longer results than, for example, other more common injectables like crosslinked hyaluronic acid (HA) dermal fillers, as they stimulate the production of collagen, which gradually improves the skin’s quality over time. Therefore, results can last for 12 months or even years, making it a more desirable option for individuals seeking lasting improvements.”

As well as results, patients are avoiding the ‘fuller’ look in search of a more natural appearance. Italian plastic surgeon Professor Maurizio Cavallini explains that, in his opinion, this is the biggest trend in aesthetics, and has been a notable shift among his patients. He adds, “Patients are now focusing on softening lines and restoring and rejuvenating the skin, without modifying the facial features. The goal is to improve skin health, maintaining a natural effect. Collagen-stimulating products are suitable for a vast range of conditions offering a real bio-generation process: a new way to rejuvenate the skin that’s very exciting!” One study highlighted that good skin quality is defined as healthy and youthful in appearance, leading to a natural look.2

According to aesthetic practitioner Dr Fabrizio Equizi, these types of injectables are another tool for practitioners to have in their practice for skin rejuvenation and preventative ageing. “All practitioners use botulinum toxin to target wrinkles and fillers to treat volume and fat loss. But, on top of that, we have skin, so anything to improve this is the icing on the cake! Collagen-stimulating injectables are the ideal solution for this to complete the overall antiageing plan,” he says.

An overview of collagen stimulators

Dr Somji explains that collagen stimulators work by energising the body’s skin healing abilities. “The products induce a controlled inflammatory response, stimulating the production of collagen and other essential proteins. This triggers the body’s natural, self-healing and self-regenerative processes. Consequently, the skin gains improved elasticity, firmness and diminished signs of ageing, such as fine lines, wrinkles and sagging,” Dr Somji says.

As well as encouraging more collagen, these injectables can help with overall skin quality – thicker, plumper, more hydrated skin.

Collagen-stimulator treatments are suitable for a wide range of patients. Of course, suitability depends on the type of product used and the patient. Dr Equizi explains, “Personally, I have found that patients that have significant volume loss would not benefit. In my opinion, collagen-stimulating products aren’t a substitute for toxin and regular hyaluronic acid fillers as patients can get a quicker and more controlled result to address wrinkles and fine lines. I believe tackling volume loss first and then addressing the skin afterwards is pivotal, as the result will look better and more refined.”

According to Professor Cavallini, the use of collagen stimulators can be applied to both younger and older patients. He adds, “In younger people, the treatment acts as a preventative action against photoageing, smoking and stress lines, as well as other extrinsic causes of skin ageing. Whilst for older patients, they represent a curative protocol against chrono-ageing, reduction of fibroblast vitality, alteration in extracellular matrix and impairment in antioxidant capacity.”

As well as being used for facial rejuvenation (Figure 1), Professor Cavallini adds that collagen stimulators can be injected in different regions of the body including the hands, neck, décolletage, buttocks, thighs and abdomen, as well as addressing acne scarring and stretch marks.

Different collagen stimulators

Collagen stimulators are commonly split into:4,5

  • Poly-L-lactic acid (PLLA)
  • Calcium hydroxyapatite (CaHA)
  • Polycaprolactone (PCL)
  • Polynucleotides (PN)

Dr Somji notes that collagen stimulators ultimately achieve similar goals but have key differences. “PLLA is one of the most extensively employed biostimulators. PLLA microparticles can stimulate subclinical inflammation in the host, which promotes collagen synthesis. CaHA relies on suspended microspheres of CaHA, stimulating both immediate and long-term tissue responses.7 It is primarily used for facial rejuvenation, including soft tissue augmentation, contouring and minimising deep facial wrinkles,” he says.

PCL, on the other hand, has a higher biocompatibility and is frequently used for volume restoration, scar correction and skin sagging improvement, Dr Somji adds. The PCL-based collagen stimulator is composed of PCL microspheres suspended in a carboxymethyl-cellulose gel carrier. This provides immediate and sustained volumising effects when injected.8

PN is the final type of biostimulator and has become a recent buzzword in the aesthetics industry. PN are comprised of DNA polymers usually extracted from male salmon trout gonads through advanced purification and high-temperature sterilisation procedures.9 Professor Cavallini reflects that it can be used to enhance fibroblast activity and skin quality. “I categorise PN as a bioregenerator because of its ability to regenerate the skin from within. As they are biopolymers, the molecules are made from fragments of fish DNA, closely resembling human DNA,” he adds.

Considerations for treatment

Protocols for a collagen-stimulating treatment will vary depending on the product used. A thorough medical history should be conducted, as well as clearly communicating the expectations and potential outcomes of the treatment to the patient, notes Dr Somji.

Contraindications should also be explained.5,8,11,12 Dr Somji comments, “It is important to assess for previous aesthetic treatments, particularly those involving injectables or laser treatments. Smoking can also negatively affect the healing process as well as collagen synthesis, whilst alcohol may increase bruising and swelling, so it’s important to be aware of this.”

Dr Somji also notes patients who have active infections or skin conditions, allergies/ sensitivities or severe medical conditions should not be treated.10 “Patients with infections or skin conditions, like eczema or psoriasis, should not be treated until the condition is resolved to avoid worsening it further. Individuals with known allergies to biostimulator substances or ingredients should also be avoided as well as patients with medical conditions, such as uncontrolled diabetes or autoimmune diseases,” he says. Dr Somji adds that patients who are pregnant or breastfeeding should not be treated.10

Dr Equizi also adds that the use of retinols and acids like tretinoin may need to be stopped before treatment. He explains, “This depends on the product you are going to use. Some sources recommend stopping retinol for a few days, whilst others require a few weeks. This is because it can cause unpredictable healing responses or skin reactions, so it’s worth looking into the product’s recommendations before use.”13

Product selection

With a variety of products on the aesthetics market, each collagen stimulator offers various benefits, as well as targeting different skin concerns and areas of the body. Professor Cavallini prefers to use the Mastelli range, with the product being selected based on the patient’s skin type. 

He notes, “For younger patients, I suggest the biostimulator Plinest (a polynucleotide product) as this prevents and maintains skin quality, whilst helping to remodel areas with high fibrous content such as acne scars. I use this for most of my patients. For mature skin, I use Newest which contains polynucleotides with hyaluronic acid (HA) and mannitol – ideal to target dehydration.”

Professor Cavallini also uses Plinest Eye and Hair for delicate, sensitive skin, like under the eyes and the scalp, which both contain a low concentration of polynucleotides. However, there are various brands of polynucleotides on the market.

Dr Somji prefers to use Sculptra in his clinical practice, in which the protocol consists of a series of PLLA injections. He notes that the product is commonly used to address volume loss and stimulate collagen production in specific areas of the face, such as the cheeks, temples, nasolabial folds and marionette lines.

When injecting the product, Dr Somji adds local anaesthetic (1ml 2% lidocaine) to the Sculptra solution prior to injection. “I use a 27 gauge needle to administer the treatment. Sculptra is constituted with an 8ml dilution (sterile water) with the lidocaine. I administer 0.1ml boluses into the target areas. There are two main depths of injection planes, subdermally and subcutaneously. Generally, I recommend two phials administered in the first session followed by successive sessions four to six weeks apart,” he reflects.

Or course, there are many other brands of PLLA and PN products available as well as PCL and CaHA, mentioned above.


As well as the above options, some HA products have also been shown to stimulate collagen production. HA plays a multifaceted role in tissue regeneration, skin repair, wound healing and skin rejuvenation.6 An analysis of the literature revealed that HA formulations exhibited antiageing and facial rejuvenation properties, achieving skin hydration, as well as collagen and elastin stimulation.6

For his product of choice to stimulate collagen, Dr Equizi uses the bioremodelling HA-based product Profhilo. The protocol consists of five intradermal injections on five predetermined sites on each side of the face. He explains, “Profhilo’s patented NAHYCO technology is not just a mixture of linear low and high molecular weight HA but a unique innovative molecule. Its thermal stabilisation makes its very stable while still maintaining its natural chemical structure and the product stays in the skin for approximately 60 days. The slow, long-lasting release directly signals skin cell receptors to produce more collagen, elastin, and the skin’s own natural HA, which is where the extra hydration comes from. Profhilo can also help to restore fat pads under the skin, which is why there is a subtle volume effect post-treatment. This is why Profhilo is known as a multi-level bioremodeller rather than just a biostimulator.”

Complications and aftercare

Much like any other injectable procedure, patients may experience swelling, bruising and redness. Professor Cavallini notes, “The mechanical action of the needle may cause minor bleeding. The swelling at the site of infiltration usually heals within a short timeframe, although it can take longer depending on the patient and the needle technique used.”

Dr Somji notes that patients should always be aware of any potential adverse events to all collagen stimulators, including infection, allergic reactions or nodule formation. “Whilst extremely rare, allergic reactions to Sculptra, for example, have been reported. Symptoms include itching, a rash, hives, swelling or difficulty breathing, so patients should be notified of all the risks and have access to an emergency contact number if this occurs.”14 He continues, “For most collagen stimulators, small nodules or lumps may occur under the skin but are typically temporary and can be minimised with proper injection technique and massage post-treatment.”14

Other complications include more stubborn nodules which may require oral steroids or antibiotics. In other cases, injections of cortisone or saline may help resolve them. As non-HA based collagen stimulators can’t be dissolved using hyaluronidase, surgical removal is a last resort for these products.14

All the practitioners recommend a broad-spectrum SPF 50 post-treatment to protect the skin from sun damage and maintain results. Dr Somji notes that intense physical activity should also be avoided 24-48 hours after treatment, as well as hot tubs, saunas and activities that increase blood flow and body temperature, helping to minimise swelling.

He adds, “Personally, with Sculptra for example, I recommend patients massage the treated areas to evenly distribute the product and prevent the formation of nodules or lumps. Patients can also apply cold compresses if they experience swelling or discomfort after a collagen-stimulating treatment. This can help reduce any swelling and provide relief.”

Professor Cavallini agrees but also recommends his patients to avoid makeup for six to 12 hours post-treatment, apply soothing creams (i.e. nucleotide-based creams) and take antioxidant-acting supplements post-procedure.


As individuals continue to age, Dr Equizi notes that results can vary from person to person. “With Profhilo for example, if a patient has had the recommended two treatments one month apart, then I would advise they continue with treatments every three to four months to reap the accumulative benefits and maintain the results,” he explains.

For Plinest, the company recommends treatment every 14-21 days for three to four sessions,15 whilst Dr Somji notes that for Sculptra, he personally recommends three sessions over three to four months. However, other collagen stimulator protocols may vary.

Furthermore, as collagen stimulators prompt collagen production gradually, it typically takes a few months to see the full effects – product depending. Dr Somji adds that the longevity of results differs according to the product, but for example, Sculptra lasts up to two years. He comments, “Individual factors, such as age, lifestyle, metabolism and the number of treatment sessions, can influence how long the results will be maintained. However, it is important for patients to recognise that these treatments do not stop the natural ageing process. Over time, the effects of collagen stimulation will diminish, and the skin will naturally continue ageing. This should be discussed in your consultations to manage patient expectations. Therefore, regular maintenance treatments can help to sustain and enhance the results over time.”

A rise in collagen stimulators

According to the practitioners interviewed, the popularity of collagen-stimulating products are expected to continue to rise. Dr Equizi advises practitioners that patient selection and setting expectations is key. He notes, “Setting realistic expectations and a careful assessment are pivotal. Collagen stimulators are not a substitute for botulinum toxin and dermal fillers but should be implemented as a skin maintenance protocol.”

Dr Somji agrees, adding that patient safety and satisfaction should remain a top priority. “By adhering to best practices, staying informed and communicating effectively with patients, practitioners can provide optimal care and achieve successful facial rejuvenation outcomes with collagen stimulators,” he concludes.

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