Aging Part 5: Collagen Stimulation Options

Welcome back friends!  If you’re reading this blog for the first time, you may want to backtrack to the beginning of our aging series to catch up on WHY our skin ages and HOW. We’ll be building upon last week’s information on collagen today. As you may remember, collagen decreases by 1% or so each year, starting as early as our mid-20’s! So by the time you’re 45, you’ve already lost 20% of your collagen!

Since collagen is the structural support of our face AND responsible also for its elasticity, it makes sense why many of us begin to see changes in our skin starting as early as our 30s.

The good news? There’s still hope! We can stimulate the production of collagen and try to prevent current collagen breakdown. Let’s get to it.

There are several ways to stimulate collagen. At Elevated Aesthetics, we have the following options:

  1. Medical grade skincare
  2. Tinted mineral sunscreen
  3. Poly-L Lactic Acid (PLLA) / Sculptra®
  4. Radiofrequency (RF) / Sublative™
  5. Medical Microneedling Pen or Device / Exceed™
  6. Radiofrequency Microneedling (RFM) / Matrix Pro®
  7. Platelet-Rich Fibrin (PRF) 
  8. PRF Gel / BioGel / ezGEL

That’s a lot of options, but not everyone is a candidate for every one of them. Moreover, each patient has unique needs that will benefit from one (or several) treatment(s) more than another. This is where a consultation with me (Tara, a board-certified Nurse Practitioner) comes in. You’ll be able to sit down, one-on-one, and share your concerns and your goals, and receive a thorough medical examination of your skin and all its underlying structures. Then you’ll receive a customized plan that’s made just for you and your needs and goals.

Now, let’s talk a little about each collagen-stimulating option…

Medical grade skincare

Research has shown that regular application of topical Vitamin C is necessary for normal collagen support. Vit C also acts as an antioxidant… oxidants are intrinsic and extrinsic substances (UV exposure, smoking, alcohol, pollution are all extrinsic examples; fibroblast senescence and the breakdown of cells are examples of intrinsic factors) that when interacting with our skin, result in the loss of hydrogen ions. This makes those cells unstable and “oxidized” which reduces their ability to make new collagen. Antioxidants like Vitamin C restabilize those cells and help hinder that process (Gold et al, 2024; Mineroff et al, 2024).  We carry 2 options for medical grade Vitamin C (and no, OTC nor even professional grade will do the job): Hydri-C by Hydrinity & Alto Advanced Defense and Repair by skinbetter. Here’s a major bombshell on Vitamin C that I shared on our IG page!

Additionally, retinols/retinoids (Vit A) stimulate hundreds of genes responsible for making collagen, among other things. “Topical retinoids treat photoaging by increasing collagen synthesis, reorganizing collagen fibers, and increasing extracellular matrix anchoring fibrils. Retinoids bind nuclear receptors and activate the expression of genes involved in keratinization” (Mineroff et al, 2024). My absolute favorite is skinbetter science’s AlphaRet Overnight Cream, which equates to a low-grade tretinoin without the irritation (it contains AHA which acts as a buffer).

Hyaluronic acid (HA) applied topically can help supplement that which is lost in the aging process (HA is a type of protein found in collagen). However, typical OTC HA serums have HA molecules that are too large to be absorbed into the dermis (where it’s needed), so it’s imperative to get an HA that hitches a ride on a carrier such as a peptide (like skinbetter’s Interfuse system or Hydrinity’s line of HA serums). Here’s a deeper dive on topical HA I did on Instagram!

Tinted Mineral Sunscreen

It is now widely known that collagen directly breaks down when exposed to UV and visible light. However, if you needed more proof, take it from the latest researchers stating, “It is now understood that UVA, IR [infrared radiation], and VL [visible light] …increase reactive oxygen species (ROS), collagen degrading enzymes, and other inflammatory cytokines” (Mineroff, 2024). Therefore, it’s imperative to wear sunscreen every day, whether you’ll be inside or outside, if you want to prevent the denaturing of your collagen! Tinted, mineral sunscreens contain iron oxides that further protect against VL in addition to the UV rays, as traditional sunscreens only protect against UV and not VL. Here’s my take on sunscreen!

Sculptra®

PLLA, or Sculptra®, first came on the aesthetics scene in 2009 when it was approved by the FDA for cosmetic purposes (it originally was approved in 2004 for facial fat loss in HIV patients). So its safety has been proven for 20 years, and its activity is therefore highly studied and predictable. Sculptra® is an injectable treatment that results in gradual results that are long-lasting; most studies have proven 2+ years of results. It stimulates fibroblasts to make new collagen. Initially it was felt this was through stimulating an inflammatory response, so there was concern about patients who have autoimmune disease and receiving PLLA safely. However, the latest studies have shown that it’s less about inflammation and actually more of a direct stimulation of the fibroblasts themselves (which is great news!).

My favorite Sculptra advocate and researcher is Dr. Shino Bay. He stated recently, “Sculptra acts as your anti-aging 401K, benefiting the integrity of your bones, fat, and skin.”

How it works:  Sculptra’s poly-L-lactic acid powder is mixed with sterile water and injected into areas that need volume and rejuvenation. The PLLA molecules are essentially bathed into these areas with the help of the sterile water. Over the next 12-24 hours, the sterile water is reabsorbed and the PLLA molecules remain. These particles act as the stimulus for summoning fibroblasts and other growth factors to the areas. Just recently, a remarkable study published by Dr. Jill Waibel and colleagues revealed that Sculptra effectively biomodulates cell behavior, and also compared it to another very popular biostimulator, CaHa (Calcium Hydroxylapetite, aka Radiesse). They found that “PLLA-SCA and CaHA have differentially expressed gene signatures and unique mechanisms of action. PLLA-SCA upregulated more genes relating to regeneration and morphogenesis, whereas CaHA was more inflammatory and pro-inflammatory.” THIS is why I use Sculptra for the face. I am not against Radiesse necessarily, but this solidified my decision. If you’re nerdy like me, I found this extra info from Dr. Shino Bay interesting in his summary on Instagram: “Gene ontology analysis suggests that PLLA-SCA primarily stimulates ECM components while inducing fewer inflammatory markers, facilitating morphogenesis and regeneration along a regenerative pathway… ELN, which encodes tropoelastin, plays a crucial role in the formation of mature elastin. Elastin, in turn, is a major component of elastic fibers, providing essential support to connective tissues… MT1A, known as Metallothionein-1A, acts as a potent antioxidant, effectively protecting against hydroxyl free radicals… CaHA-R, however, elicits a stronger inflammatory response that could potentially hinder tissue regeneration, following a pro-inflammatory pathway.”

I have personally received Sculptra® from my personal injector (shout out to Kelly!) and I can honestly say this treatment transformed my face in the best way. I still look completely natural and like “me,” but it has restored the volume I had lost as a postmenopausal female. My skin’s elasticity and overall health is the best it’s been in 20 years. I’m a huge believer in Sculptra® not only because of my personal journey with it but also in seeing what it’s done for my patients since beginning to inject it over a year ago. I have to say, for collagen stimulation, it’s probably one of my favs. There is a risk for forming nodules with Sculptra, but it’s fairly uncommon.

Check out my video summary on it HERE.

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Traditional Microneedling / Exceed™ pen

You may have heard of (and maybe even tried!) dermarolling, a home device that creates small punctures into the skin. This method of skin rejuvenation is no longer recommended as much due to variability in how people use these at home (ensuring correct use, depth, frequency, and controlling for factors like minimizing injury & infection). The notion of micro-injuries, however, is still very much alive and the literature is growing with regard to microneedling’s benefits. Regular microneedling sessions in an aesthetic setting can address a multitude of issues, including stimulation of collagen!

How does it work?  When the microneedles penetrate to the dermal layer of the skin, it results in a controlled, localized injury which causes a release of growth factors (ie, TFG-alpha, beta, VEGF, PDGF). These growth factors stimulate the production of collagen and elastin fibers (Dayan, et al, 2019).  In a study done by El-Domyati and colleagues, biopsies done at baseline and after 6 microneedling sessions at 2-week intervals showed significant increases in the levels of “collagen type I, III, and VII, newly synthesized collagen and tropoelastin” (Singh & Sadav, 2016).

Does it really work??  “Histological examination of the skin treated with 4 microneedling sessions 1 month apart shows up to 400% increase in collagen and elastin deposition at 6 months postoperatively, with a thickened stratum spinosum and normal rete ridges at 1 year postoperatively.” (Singh & Yadav, 2016).

Radiofrequency (RF) / Sublative™

RF is an “oscillating electrical current that induces collisions between charged molecules, which generate thermal energy… RF energy has a uniquely electrothermal effect rather than a selective photothermal effect like lasers, which target specific chromophores. Therefore, RF energy can be used in all skin types regardless of pigmentation, whereas lasers should be used with caution in patients with darker skin” (Magro et al, 2022).

How does it work?  When RF energy is applied to the skin, it causes immediate & delayed tissue contraction of the skin. In the immediate treatment phase, it shortens and thickens collagen fibers. Then, over the next 3-4 months, a delayed tissue contraction response occurs from inflammation induced by the treatment; this inflammation triggers a wound healing cascade ultimately leading to fresh collagen formation. In addition, the RF energy heats up the dermal collagen while protecting the epidermis from injury. This heating of the collagen is needed to break down the now-poorly-arranged/aged collagen tendrils in order to allow the fresh collagen to form fibers that are more tightly bunched together. (Magro et al, 2022).

Radiofrequency Microneedling (RFM) / Matrix Pro®

RFM has been around for quite a while now, but it’s better than EVER with the latest technology with Candela’s Matrix™ system. The Matrix Pro® combines the power of short-pulse RF energy and microneedling with the thinnest array of microneedles on the market. It sets itself apart from other competitors, like the Morpheus8, by allowing me (the provider) to adjust the depth of the needles to be more precise, and provides me real-time feedback so I can adjust my settings once I’m in the treatment phase. The benefit of this is that unlike Morpheus8 and others, I can ensure I’m not breaking down a beneficial fat pad (an issue that is really plaguing other competitor RFM devices/users right now!) or doing more harm to the tissues than needed.

How does it work?  RFM works by causing a “controlled injury” to the tissues. In doing so, the fibroblasts and other healing components are sent to this area to “repair” it, and as we all know by now, those trusty fibroblasts stimulate the growth of new collagen! “RF microneedling systems advance existing technology by adding heat at controlled depths,” according to Dayan and colleagues (2019). This heat is important, as it is the impetus for even more collagen & elastin formation than microneedling alone.

Does it work? “Studies have shown active dermal remodeling by 10 weeks post-procedure with increased reticular dermal volume, hyaluronic acid, and elastin content” (Dayan, 2019). They proved RFM effectiveness in taking biopsies of the skin before, immediately after, and 4 months after RFM treatment in the study by Dr. Suh & colleagues in 2022, and it showed excellent improvement in the tightness & thickness of collagen bundles, presence of new collagen, and new elastin formation 4 months later.

Does it last?  In his 2021 research, Dr. Tan and his colleagues found that “Radiofrequency microneedling-induced dermal remodeling and neocollagenesis are slow and progressive but continue to improve even 6 months after treatment.” Imagine getting a treatment that, 6 months after you’ve done it, it’s still working!

Platelet-Rich Fibrin (PRF)

We are proud to be the first aesthetics practice in Wayne County, NC to offer PRF. Our bodies’ ability to regenerate its own tissue – in this instance, collagen & elastin – never ceases to amaze me.  PRP (platelet rich plasma) has been used for years, and just in the last few years they have improved upon that process with PRF as “the new PRP generation that is richer in growth factor concentration, enabling it to have a significantly better outcome in stimulating angiogenesis, tissue regeneration…  [and inducing] mesenchymal stem cell (MSC) migration to the site of injection, which bears imperative regenerative function” (Mahmoodabadi et al, 2023).

What is it?  We draw a couple tubes of blood, spin it down in a centrifuge, and then draw out the PRF that results at the top of the tubes. This is then injected (or microneedled!) into the skin where fresh collagen is needed.

How does it work?  The PRF stimulates the migration of fibroblasts to the area by 350%, inducing collagen formation. It also significantly increases the levels of other important growth factors like PDGF mRNA, VEGF, TGF-β1, collagen 1, IGF, and fibronectin mRNA; these growth factors further stimulate mesenchymal stem cells to produce new collagen (Majewska, 2023; Wang, 2019). “PDGF is considered the critical trigger of the tissue repair process, and contributes to the proliferation of fibroblasts and other mesenchymal cells. VEGF stimulates the synthesis of blood vessels and the basal lamina and enhances the microvascular permeability. TGF-β1 regulates cell motility, differentiation, and proliferation, and plays an important role in physiological repair by promoting collagen production and accumulation. Characterization of the biological properties of different platelet concentrates in vitro revealed that PRF contains greater amounts of released TGF-β1 and results a prolonged release of growth factors and stronger induction of cell migration. IGF promotes mitosis and the proliferation of fibroblasts” (Wu et al, 2022).

PRF Gel / Bio-Gel / ezGEL

At Elevated Aesthetics, we use ezGEL brand for a “natural filler” option that can also stimulate collagen. I always say, “it’s like filler & Sculptra had a baby.” I can’t really substantiate those claims (LOL), as they haven’t compared the neocollagenesis between ezGEL and Sculptra, but the premise makes sense when explaining it to my patients 🙂

What is it?  Basically, ezGEL takes PRF just a step further. Both of the tubes of blood are centrifuged; one of the tubes is heated, while the other is cooled. Once the heated tube’s contents is warmed to 75º C, it forms a gel (similar to a very soft filler consistency). Studies have shown that at that temperature, the proteins remain intact but are able to form a usable matrix to trap the PRF growth factors in place! We then mix the PRF and the gel into one smooth mixture to inject it where needed.

How does it work?  “The gel serves to localize both activated platelets and their presynthesized growth factors in the treated area. The platelets trapped in the gel continue to synthesize and release bioactive growth factors after injection. These growth factors interact with the undifferentiated adipose-derived stem cells and dermal fibroblasts by binding to their specific cellular receptors promoting neovascularization and neocollagenesis, resulting in soft-tissue augmentation and reduction of wrinkles. It is suggested that the continual release of growth factors from trapped platelets at the injection site may be responsible for the sustained therapeutic effects of plasma gel for several months after the treatment session. These growth factors also enhance synthesis of extracellular matrix components such as hyaluronic acid. The contraction of myofibroblasts around wrinkles causes skin tightening and strengthening” (Gupta et al, 2020).

I often will recommend ezGEL over PRF if we are considering doing filler but also need to do some collagen stimulation, as an alternative to Sculptra. The results have been amazing, particularly in areas we cannot inject Sculptra such as under the eyes & around the mouth.

As a side note, I love combining these options above… here’s an example!

SUMMARY

Clearly, I’m passionate about collagen stimulation!  We often refer to this area of aesthetics as biostimulation or regenerative medicine. I am proud that Elevated Aesthetics’ renewed focus is on natural approaches for natural results. While we’ll never stop offering neuromodulators like botox or fillers like Restylane, I see (as many other aesthetic experts do) that the world of biostimulation is the future of aesthetics, and I am ecstatic to be leading the way for our area and for my patients in biostimulation. Collagen ultimately creates a happy patient, and a happy patient means a happy aesthetic provider!

References

Dayan E, Chia C, Burns AJ, Theodorou S. Adjustable Depth Fractional Radiofrequency Combined With Bipolar Radiofrequency: A Minimally Invasive Combination Treatment for Skin Laxity. Aesthet Surg J. 2019 Apr 8;39(Suppl_3):S112-S119. doi: 10.1093/asj/sjz055. PMID: 30958550; PMCID: PMC6460431.

Gold M, Andriessen, A, Burgess C, Callender V, Goldberg D, Hougeir F, Kircik L, & Schlesinger T. Promoting a Healthy Skin Barrier Using Skin Care in People With Mature Skin Xerosis. J of Drugs in Derm. 2024 Jan; 23(1): 1253-1259. doi: 10.36849/JDD.7560.

Gupta S, Borde Bisht P, Kannan C. Bio-Filler: An Effective Facial Rejuvenation Tool-Easy on Pocket. J Cutan Aesthet Surg. 2020 Jul-Sep;13(3):243-246. doi: 10.4103/JCAS.JCAS_172_19. PMID: 33209005; PMCID: PMC7646418.

Magro I, Kochhar A, Arnaoutakis D, & Karimi K. Transcutaneous Radiofrequency Microneedling in the Facial Plastic Surgeon’s Practice: A Review. Facial Plastic Surgery & Aesthetic Medicine 2022 24:S1S-3-S-10. doi: 10.1089/fpsam.2022.0226
Mahmoodabadi RA, Golafshan HA, Pezeshkian F, Shahriarirad R, Namazi MR. Evaluation of the Effect of Platelet-Rich Fibrin Matrix in the Correction of Periorbital Wrinkles: An Experimental Clinical Trial. Dermatol Pract Concept. 2023 Jan 1;13(1):e2023050. doi: 10.5826/dpc.1301a50. PMID: 36892335; PMCID: PMC9946120.
Majewska, LidiaPlatelet-Rich Fibrin as an Effective Method of Skin RevitalizationDermatologic Therapy2023, 9040608, 4 pages, 2023https://doi.org/10.1155/2023/9040608
Mineroff J, Nguyen JK, Jagdeo, J. The Importance of Photoaging Prevention in All Skin Types: An Update on Current Advancements. 2024 Jan; 23(1): 1306-1310. doi: 10.36849/JDD.7560.
Singh A, & Yadav S. Microneedling: Advances and widening horizons. Indian Dermatol Online J. 2016 Jul-Aug;7(4):244-54. doi: 10.4103/2229-5178.185468. PMID: 27559496; PMCID: PMC4976400.

Suh DHCho MKim HSLee SJSong KYKim HSClinical and histological evaluation of microneedle fractional radiofrequency treatment on facial fine lines and skin laxity in KoreansJ Cosmet Dermatol20232215071512. doi:10.1111/jocd.15614

Tan, Marcus G. MD; Jo, Christine E. BSc; Chapas, Anne MD; Khetarpal, Shilpi MD; Dover, Jeffrey S. MD, FRCPC. Radiofrequency Microneedling: A Comprehensive and Critical Review. Dermatologic Surgery 47(6):p 755-761, June 2021. | DOI: 10.1097/DSS.0000000000002972

Waibel, JillNguyen, ThuLe, JenniferZiegler, MaryWidgerow, AlanMeckfessel, Matthew et al. A randomized, comparative study describing the gene signatures of Poly-L-Lactic Acid (PLLA-SCA) and Calcium Hydroxylapaptite (CaHA) in the treatment of nasolabial folds. (2024). Journal of the American Academy of Dermatology, Volume 91, Issue 3, AB110. 

Wang XYang YZhang YMiron RJFluid platelet-rich fibrin stimulates greater dermal skin fibroblast cell migration, proliferation, and collagen synthesis when compared to platelet-rich plasmaJ Cosmet Dermatol20191820042010https://doi.org/10.1111/jocd.12955

Wu, Qing-Yun1; Zhang, Qian2; Fang, Fang2,*; Bu, Wen-Bo2,*. Clinical Application of Platelet-Rich Fibrin in Dermatology. International Journal of Dermatology and Venereology 5(3):p 160-165, September 2022. | DOI: 10.1097/JD9.0000000000000186.

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