Biostimulatory injectables, as the name suggests, stimulate collagen production. These injectables differ from dermal fillers which address volume loss over time. Biostimulants work by providing re-hydration to the dermal layers of skin, in addition to collagen stimulation. This slows down the aging process. In some, but not all patients, there is an improvement of skin laxity with clinically visible skin firming & tightening.

Biostimulatory injectables; summary

• Biostimulators increase collagen production & or improve skin hydration
• The aim of biostimulation is to stimulate your skin to produce collagen
• At the very least skin aging can be slowed down with biostimulants
• Some patients will get a reversal of aging, meaning clinically visible skin tightening
• The ideal injectable formulation depends on your skin’s age & health
• These injectables are compatible with lasers, RF & HIFU
• The ideal age to start bio-injectable treatment is in the early 30s

Why do we need biostimulators?

Over time, both hyaluronic acid & collagen levels diminish in your skin. Stimulators, as the name suggests, provide stimulation of your skin cells to produce collagen, elastin & hyaluronic acid.

Stimulation of collagen can help tighten or at the very least maintain your skin’s turgor & tensile strength.This prevents skin laxity & skin sagging. The type of collagen stimulating biostimulator depends on many factors, including your age & condition of your skin.

What is the difference between dermal fillers & biostimulators?

Dermal fillers provide structure & volume changes, whilst the aim of biostimulators is to provide skin hydration & tightening with minimal volume changes. This is especially important in more mature patients who hold excess volume in key areas such as the lower face, jawline & jowls. In this patient subtype, we do not want to add volume but to TIGHTEN.

What is the aim of biostimulation – what will I look like?

Unlike dermal fillers that give a perceivable change in volume, biostimulation is more subtle. It works on the principle of mitigation (something that you do not see).

The primary goal is to prevent further collagen loss & skin saggingas levels drop by 1-1.5% per annum starting from 20 years old.

The secondary goal is to reverse age associated skin laxity by stimulating collagen production. Not everyone will achieve this secondary goal, as it depends on your immune system. For those who require more collagen stimulation, lasers & energy devices can be added to the program.

How long does it take to perform & is it painful?

Biostimulatory injectables take less than 3 minutes to perform. Depending on the location & type of injectable, I use either a needle or a cannula.

Treatments are well tolerated. For needle phobic patients, I use laughing gas (for the patients, not me).

How often should I get biostimulators done?

Guidelines by one company suggest twice a year, however this is referring to hyaluronic acid biostimulators (which is different from HA dermal fillers, as this lasts a lot longer). More powerful stimulators include PCL or CAH. As a guide-

• First 12 months: 2 lots of HA biostimulator + 2 -3 rounds of non-HA biostimulator.
• Every year thereafter under the age of 45: 2 rounds of HA + 1 round of non-HA biostimulators.
• Every year thereafter over the age of 45: 2 rounds of HA + 2 rounds of non-HA biostimulators.

*Ideal type, amount & frequency of injectables depends on facial volume, skin laxity, degree of deep dehydration, age, & expectations.

** For significant sun damage, up to 3 injections are required for optimal outcomes.

What is the best biostimulator for my skin?

The best biostimulator depends on the application. Here is a simplified algorithm-

• For correction of hydration: High & low molecular weight HA biostimulator
• For correction of volume over hydration: PLLA, CAH
• For collagen stimulation with little changes in volume: PCL

For younger patients who do not require hydration correction, it is between PCL & PLLA. For more mature patients, it is HA PLUS either PLLA or PCL, depending on the volume required.

Does that mean I won’t require dermal fillers?

No. Everyone can benefit from biostimulatory injectables, however not everyone will benefit from dermal fillers. For patients who have defects in key areas (such as the jawline, cheeks, tear trough & temples), dermal fillers can make a difference.

At what age should I consider biostimulatory injectables?

Patients in their late 20s to early 30s can benefit from biostimulatory injections. Remember, the peak collagen levels occur at twenty years of age, after which your collagen breaks down at 1 to 1.5% per year.

Menopause accelerates collagen depletion, with as much as 30% loss over a span of 5 years.

How am I different from other injectors when it comes to biostimulatory injectables?

Each patient has a bespoke approach. I consider the degrees of collagen & HA loss, sun damage, age & ethnicity. From there I work on the algorithm of finding the best injectable for the problem, then work on the concentration of the active (HA, PLLA, CAH, PCL, polynucleotide). The last step is to place the injectable in key areas, considering clinical findings.

Timing intervals & concentration is essential to outcomes. It is not a cookie cutter approach.

Will biostimulators give me a face lift?

Only 2- 5% of patients will have a marked skin lifting or skin tightening effect. Biostimulators are not substitutes for face lifts, CO2 lasers or deep phenol peels, they are designed to provide low level collagen (& hyaluronic acid) replacement & stimulation, aimed at mitigating collagen loss over time.

Clinically significant tightening & face lifting is a bonus that can be seen in a minority of cases.

Are biostimulators a substitute for laser resurfacing?

No. If you have poor skin quality, namely sun damage, pigmentation, medium to deep wrinkles & enlarged pores, laser resurfacing will give you more predictable & profound results. Lasers are termed as high level biostimulation, namely they will reverse your skin’s chronological age, whilst biostim. Injectables are termed low level biostimulants.

The best lasers to reverse skin aging are CO2 lasers, followed by erbium, fractional & hybrid lasers.

What do I combine biostimulators with?

Biostimulatory injectables primarily act in the lower dermal layer of the skin. For effective skin rejuvenation, the necessary areas of skin will need to be addressed. These combination procedures work by reversing the signs of aging. As a guide;

• Textural changes including sun damage & pigmentation: fractional & pico lasers + biostimulators.
• Skin tightening & specific contouring: HIFU – Ultherapy (off label) + biostimulators
• Marked sun damage & deep wrinkles: CO2 laser resurfacing + biostimulators
• Mild skin laxity & early changes: NuEra or TriLift DMS + biostimulators
• Lower face laxity due to hyperactive muscles: Injectables + biostimulators
• Bone relaxed volume loss: High g-prime fillers + biostimulators

What are other ways to stimulate collagen production if I don’t want injections?

Your choices are limited to time tested methods such as lasers & devices, or things that won’t work but may make you feel better (collagen supplements). Collagen stimulation can be achieved with –

• Laser: Fraxel, Co2 lasers, erbium lasers
• Deep peels: TCA Jessner, Phenol
• RF microneedling & HIFU devices

*In the scheme of things your body can only make up for a small deficit in collagen loss, usually 1-3 mls. In patients over the age of 45, supplementation with collagen stimulating injectables are required to make a clinical difference. Your call.

What does a simple collagen stimulating routine look like?

Neocollagenesis can bemaintained with the following-

Low level biostimulatory methods such as;

HA bio remodeller (2 times a year) + PCL collagen stimulating injectable (once a year)

• RF or DMS such as NuEra, Trilift or Pelleve
• Home retinol or retinoid of choice (marginal gains)

Neocollagenesis can be augmented with-

• Lasers
• HIFU
• RF microneedling
• Ellacor or micro coring
• Deep peels

From there, patients go onto the low level biostimulatory routine.

What is Rejuran, a polynucleotide injectable biostimulator?

This injectable is new for Australia, having TGA approval as of 2023. Rejuran contains DNA from salmon sperm (true) & is termed as a polynucleotide (long chains of amino acids). It has a very long safety record in Asia as it has been in use for the past 8 years. In summary-

• Superficial injections under local anaesthetic cream
• Expect blebs for 36 to 48 hours (longer recovery than Profhilo)
• Best for very fine lines & wrinkles in all areas of the face
• Stimulates collagen over time, with minimal if any volume increases
• Requires 3- 4 sessions, with repeat 1-2 sessions annually
• Rejuran be combined with Profhilo for better outcomes

How does retinol rate as a biostimulator?

Dismally, in the scheme of things. Retinoids including retinol are powerful molecules that are frequently prescribed by dermatologists. Do they produce collagen? Yup- measurable in a laboratory petri dish. Will they provide a clinically significant tightening, firming, or lifting effect? Only if you are super lucky.

Retinol is best employed as an agent to improve skin quality, namely fine lines, pigmentation, sun damage & textural irregularities. Despite the marketing jargon (of which I have been guilty of), they do not provide reliable (& clinically significant) increases in collagen. Skin care however provides hope & self-care, which leads to self-love. Which is important. For fine lines, biostimulators such as Rejuran will provide far superior outcomes.

Can collagen supplements work to stimulate or replace collagen?

Highly unlikely, however given the banal nature of collagen supplements (& the low cost), you can give it a go. Collagen supplements can be good for joint health, so you have nothing to lose.

  Viewpoint on biostimulatory injectables

The most challenging concept to understand is that not all biostimulator injectables are dermal fillers, however some dermal fillers, when mixed in correct hyper-diluted concentrations, can act as biostimulators. The aim of biostimulation is to provide varying degrees of ‘skin tightening’ or fibrosis, coupled with varying degrees of skin hydration & dermal – subcutaneous volume. The primary aim of these injections is to slow down the aging process by stimulating your cells to produce collagen. Some patients can expect to get skin firming, tightening & lifting.

Depending on the clinical scenario, I pick one of four main biostimulators- hyaluronic acid, calcium hydroxyl apatite, polycaprolactone & poly-L-lactic acid based.

Hyaluronic acid, non-cross linked, heat stabilized high & low molecular weight biostimulators are useful in providing dermal (and subdermal hydration), followed by fibrosis & a wee bit of cumulative volume (yes, I know the half-life is 30 days). The most well-known biostimulator is Profhilo.

As to the degree of fibrosis (collagen stimulation), it is far less than the degree of immediate dermal hydration (replacement of hyaluronic acid), volume is not as much as the usual PLLA & CAH group of biostimulators – biomodulators. My recommendation is that this injectable is invaluable, as we undergo an age-related depletion of hyaluronic acid. This cannot be replaced with other biostimulators.

PLLAor Sculptra& CAH or Radiesse, I will group together. Both are time tested OG of the biostimulation world with nearly two decades of data- compare that with 12 months with Profhilo, at least in Australia. Dilutions matter. Undiluted CAH provides lift (high G prime), diluted, it is useful as a biostimulator. PLLA or Sculptra? Swiss Army knife depending on the marketing angle of Galderma. Undiluted it produces volume- hence TGA approved & Medicare subsidized for lipoatrophy in HIV, & Medicare does not subsidize anything cosmetic 🙂. Diluted it produces biostimulation (surprise in 2022!). As for skin quality? If you are following guidelines of one vial (min of 9 ml) for every decade of life, that equates to 6 vials (and 5.5 K USD) for improving skin quality! Can I get a better improvement in skin quality with TCA (cost price of around 4 bucks)? 100% yes. Regardless, I do employ PLLA for those who are volume depleted & require some form of biostimulation, much less so for skin quality improvements.

PCL or polycaprolactone. This is the sweet spot as of 2023. My (& Van Park) biostimulator of choice. Why? Because we both do not want to add volume but concentrate on two aspects- hydration & biostimulatory fibrosis.  Hydration (as we have a combined age of one century & our HA levels are down) is sorted with high and low molecular weight HA bio remodeler. That’s a no brainer; 2 sessions over 12 months- hydrated & dusted. Fibrosis or skin ‘tightening’ without volume, & without hydration is provided with PCL. Our choice is the new PCL formulation that is made in Korea. Microparticles in a 1.2 ml dilution that is hyper diluted to 2 ml, delivered via a cannula in our vectored locations. Twice a year provides low level biostimulation (coupled with RF & DMS or EMS technology).

Rejuran or polynucleotide is the very latest biostimulator to be approved in Australia as of 2023. This molecule is injected superficially, hence it has a little longer downtime compared to Profhilo (up to 48 hours with Rejuran). It is derived from salmon DNA via gonads. Treatment protocol is 3-4 sessions spaced 4 weeks apart. It is more biased towards collagen production, with little changes in skin volume.

Low level adjunctive biostimulation via energy devices compounds the effects of biostimulatory injectables. These can be delivered via low level radiofrequency (as opposed to high level RF from microneedling RF or HIFU).

Though there are no studies to confirm or deny the limited efficacy of high level biostimulation over time, I am a firm believer that collagen production follows the law of conditioned reflex, namely if you hit something hard enough over time, it will stop working. Thus, for continued collagen stimulation low level devices are advocated, whilst high intensity energy devices such as focused ultrasound & high energy RF- lasers are used only when required.

The future looks bright when it comes to biostimulation, however I suspect there is an inverse relationship between agents that are minimally inflammatory & that of maximal fibrosis. Said in another way, the more potential irritation one has, the greater the degree of collagen stimulation. Perhaps the sweet spot will be truly hybrid injectables in the future- combining HAs with non-HAs, which is what we are currently doing.