Once a year, leading medical experts in aesthetics worldwide convene to examine beauty trends, delve into the medico-scientific contributions that medical aesthetics can offer patients, and articulate their vision for elevating the quality of life. The Merz Aesthetics Expert Summit (MEXS) stands as an annual gathering organized by Merz Aesthetics. This year, the focal point was "Regenerative Aesthetic." In response to the global shift in aesthetic preferences towards "natural beauty," Merz anticipates that regenerative aesthetics will emerge as the industry's new cornerstone, empowering individuals to optimize their natural beauty by enhancing their skin's inherent ability to regenerate. In a forthcoming series of three articles, we will explore the value and prospects of regenerative aesthetics through insights shared by experts we encountered at MEXS 2023 in Barcelona, Spain, held in November. -- Ed.

With the recent emergence of regenerative aesthetics as the mainstream, many filler formulations are attempting to transition to “biostimulators.” These range from polymers, such as poly-l-lactic acid (PLLA) and polycaprolactone (PCL), to hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) formulations.

However, Australian plastic surgeon Dr. Niamh Corduff highlights only the CaHA formulation (Radiesse in the brand name), stressing that it "works differently from the other bio stimulator ingredients.”

Unlike other ingredients that only induce collagen production through a “repair” mechanism, CaHA works through a “regeneration' mechanism” to induce the production of the overall building blocks needed for skin tissue, she pointed out.

Korea Biomedical Review caught up with Dr. Niamh Corduff to learn more about how CaHA works as a biostimulator, the differences in side effects, and the clinical value of CaHA formulations in regenerative aesthetics.

Question: The concept of a biostimulator is fairly new.

Answer: "Biostimulator" literally means anything promoting cellular activity. This includes CaHA and many other products, but the key is the mechanism by which it can promote cellular activity.

For example, PLLA (a polymer) can help your body produce more collagen but doesn't offer any additional benefits. CaHA, on the other hand, induces not only collagen but also elastin, proteoglycans, and angiogenesis, which are the building blocks of the skin's structure and are involved in tissue regeneration. When it comes to skin regeneration, more collagen is not always better. Cells don't need so much collagen. Understanding these principles of skin regeneration and knowing how they work medically and biologically is key to regenerative aesthetics, and biostimulators are an important part of it.

Q: You have been working in regenerative medicine for the past decade. We are curious about what made you focus on CaHA preparations in particular.

A: CaHA preparations have been used for more than 20 years, and I have heard many stories about their effectiveness in improving skin texture for a long time. Especially in the past 10 years, I became curious about the principle of CaHA's skin improvement effect while looking at past cases related to CaHA. On that occasion, I am researching to determine the effectiveness of CaHA scientifically. I have established basic concepts to an extent and am working on further research to refine them.

Q: How does CaHA work as a stimulator?

A: The skin has an "extracellular matrix" and "main cells." The main cells include fibroblasts and stem cells, closely associated with the extracellular matrix. When the main cells come into contact with the extracellular matrix, they activate regenerative mechanisms with the proliferation of various cells. In regenerative aesthetics, the extracellular matrix generates new cells and regenerates a healthy structure.

Let’s look at CaHA's mechanism step by step. First, CaHA binds easily to cells in the body because CaHA is an abundant component of the human body. It easily connects with cells. Recent studies have shown that cells (fibroblasts, stem cells) bind easily and respond effectively to CaHA microspheres as they stretch and unfold. This is not the case with other biostimulants, and the similarity of CaHA to the human body makes it easy to bind to the body's receptors.

Next, the immune system recognizes and responds to CaHA. The immune system is responsible for responding to threats to the body's environment and repairing damage to the body. Since CaHA is a biomaterial, the immune system recognizes it as part of the body. It builds new structures, i.e., produces collagen, elastin, and other components, and the immune system's regenerative process begins.

Preclinical studies (in vitro) have shown that macrophages respond differently to CaHA and PLLA. In the case of PLLA, macrophages have released inflammatory mediators and triggered a "foreign body response" involving multiple cells. In the case of PLLA, macrophages release inflammatory mediators, and other cells intervene, triggering a "foreign body response." This is known as the "repair progress" response, in which large amounts of collagen are produced to ward off threatening substances. The collagen will wrap tightly around the cell until the foreign body reaction passes. CaHA, on the other hand, is compatible with the body's immune system, meaning that the body recognizes it as "on the same side" and produces a variety of cells to provide the necessary components. Healthy fibroblasts come into direct contact with the CaHA and build new structures, creating a new extracellular matrix.

In the third step, the microspheres are broken down into very small granule cells, then broken down even further and delivered to the extracellular matrix, the space in the skin that becomes stretched and loose due to aging. These tiny microspheres connect with fibroblasts, creating a calcium-rich environment for producing fibroblasts, collagen, and other components. These complex phenomena interact to produce regenerative aesthetics.

Q: If the mechanism of action is different, one might expect the adverse events to be different.

A: Due to the biocompatibility of CaHA preparations, most adverse events are caused by negligence during the injection phase rather than by the product itself. These include bruising when injected into the wrong layer of skin or nodules when the dilution method is not properly followed. Nodules may occur if not properly diluted with saline. Still, they are not the same as inflammation and can be resolved by scrubbing the area well after injection.

Side effects are usually minimal if you follow these instructions. In rare cases where side effects are severe, they are mostly cosmetic rather than biological. From a biological point of view, the immune system recognizes CaHA preparations similarly to the immune system, which is why they don't cause significant problems in the long run and why problems with other polymer products are rarely seen with CaHA preparations. According to the FDA database, no significant adverse events are associated with CaHA formulations.

Q: Is there a specific reason you recommend CaHA preparations to your patients in clinical practice over other options?

A: The strength of CaHA formulations is natural skin improvement. I expect it's similar in Korea, where my main emphasis as a clinician is natural skin with a bright, healthy glow, like baby skin. Compared to other biostimulators, CaHA formulations are superior in this regard. With CaHA, treatments can be performed with a natural, unobtrusive effect that will improve the appearance of the skin over time.

Unfortunately, the same cannot be said for PLLA. PLLA also produces collagen and increases volume, but it does so through a different immunologic mechanism than CaHA. This is very different from the natural collagen normally produced by the skin, so new skin structure cannot be achieved.

Q: What is your definition of “beauty,” as you greatly emphasize “natural beauty” in explaining regenerative aesthetics and CaHA?

A: I think beauty is about instilling confidence in patients so that they can find their “best selves.” Small changes in self-perception can make a big difference. How you perceive yourself can change how others see you at home or work. Therefore, I believe true beauty is about breaking away from the unified beauty standards imposed by our society and finding a way to stand out and gain confidence.

Ultimately, when you find confidence in yourself, you can feel and live a better life by being happy with yourself. I believe that helping patients regain confidence in themselves is the ultimate goal of medical professionals, and I am always thinking about how I can help patients in a similar vein.