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Articles Highlight Role of Calcium Hydroxylapatite in Regenerative Aesthetics

Article-Articles Highlight Role of Calcium Hydroxylapatite in Regenerative Aesthetics

Sponsored by Merz Aesthetics The phrase ‘regenerative aesthetics’ (RA) is a new buzzword in the industry, and with good reason. It promises the use of the body’s own natural processes for healing, restoration and retention of youthful appearance and vigor.

Sponsored by Merz Aesthetics

The phrase ‘regenerative aesthetics’ (RA) is a new buzzword in the industry, and with good reason. It promises the use of the body’s own natural processes for healing, restoration and retention of youthful appearance and vigor. Leaps forward in the overall field are occurring within aesthetic medical science, driven by a ravenous marketplace.

A strong definition of RA is shared in a 2023 review article by Katherine Goldie, MD1 initially pointing out that it is primarily concerned with restoration of soft tissue compromised by the aging process and its impact on aesthetics. More succinctly, RA is the recreation of structurally youthful soft tissue “which positively impacts aesthetic outcomes,” according to the Goldie review article.1

Challenges are numerous and complex when considering the aesthetic goals of RA alone, the Goldie paper explained.1 The environment of senescent tissue is complex and there are hurdles every step of the way because both the structure and function of tissues are being compromised during the aging process. At the macrolevel there is reduced barrier function and integrity, while cells become dysfunctional and senescent at the microlevel. Each factor is interconnected and interrelated. There is degradation of structural components such as collagen and elastin as well as the microcirculatory network, which reduces the efficacy of basic mechanisms. Reduction in key cells as we age, such as fibroblasts, contribute to this degradation of the extracellular matrix (ECM) providing tissue with structure, along with concurrent stimulation of pro-inflammatory pathways and apoptotic dysfunction. This puts a spotlight on the delicate balance between healthy regenerative processes and healthy cell turnover.

According to Goldie1 we currently have three significant, distinct vectors through which RA is performed including the use of bio-cues, which harness cell signaling mechanisms to create a more advantageous local tissue microenvironment; cells, which include the use of stem cells or tissue fractions containing them, such as the stromal vascular fraction (SVF) derived from fat – which has been going on in aesthetic medicine for some time – and the use of regenerative scaffolds, a more novel approach in the space.

Calcium hydroxylapatite (CaHA) is marketed as Radiesse from Merz North America (Raleigh, N.C.), an injectable filler with dual properties of direct filling and biostimulation. Radiesse is CaHA microspheres suspended in a carboxymethylcellulose (CMC) gel which, when injected, stimulates regeneration of collagens I and III as well as elastin and proteoglycans, according to an article by Shino Bay Aguilera, DO, et al. (2023).2 The CMC gel provides an immediate filler effect while implanted CaHA microspheres stimulate neocollagenesis, replacing the artificial effect of the CMC gel with natural tissue over time.3 Thus Radiesse fundamentally improves skin structure and quality, restoring a more youthful look to skin.

The CaHA mechanism of action has low inflammatory potential, according to an in vitro study by Bartosch Nowag, MD and colleagues in 20233 in which primary human macrophages were incubated with CaHA or poly-L lactic acid (PLLA) and screened using an inflammation array. This demonstrated a differentiation of the biostimulatory pathways of the two products. Study authors called attention to the fact that the immunological pathways in biostimulation help direct the outcomes in key aspects. These affect specific elements such as the ratio of collagen types, elastin, glucosaminoglycans and other aspects of the ECM which will impact the structure and function of soft tissue – the very foundation upon which RA’s success depends.

The process of scaffold formation in wound healing provides a framework for understanding this. According to a review article by Niamh Corduff, MD4 Phase 1 is the initial injury and scaffold formation. The injury initiates the healing cascade, including an inflammatory response, leading to clot (thrombus) formation. Phase 2, inflammation and initial foreign body response, drives one of two healing pathways – inflammatory slowdown (M2), which promotes tissue remodeling, or pro-inflammatory (M1), which promotes further reactions to handle contamination, or if the wound is particularly traumatic. During Phase 3 we see remodeling (if threats have been resolved) or ongoing chronic inflammation, and Phase 4 is where final remodeling takes place. A smoother pathway with less inflammation yields healthier tissue that more closely resembles pre-injury tissue in structure and function; more inflammation leads to various types of lower quality tissue, known as scars. As explained by Dr. Corduff, “Anti-aging aesthetic medicine uses interventions like biomaterial-based fillers to influence these immunological responses and renew aged tissue structure and function.”4

A systematic review of the skin regeneration mechanisms of CaHA by Mojgan Amiri, et al. (2023) chose 12 studies from a pool of 2,935 based on extensive criteria.5 Collective findings regarding cell proliferation, neocollagenesis, elastin, angiogenesis and other aspects were discussed. According to the review article CaHA may positively affect cell proliferation, and appears to induce synthesis of collagen types I and III at various stages. Elastin, which contributes to the youthful elasticity of healthy skin, was also shown to increase after injection of CaHA, although the effect may be time-dependent, and more research is needed. Stimulation of angiogenesis was also a consistent finding, important given the role of microcirculation in tissue regeneration and maintenance processes.

The rheological properties of Radiesse itself are also advantageous – with a high elastic modulus (G prime; G ), measuring firmness or rigidity) and complex viscosity ( *, measures resistance to flow) – according to the Aguilera review.2 But more importantly these properties may affect the outcomes. This maintains injectability while maximizing support structure and mitigating potential for migration.

A treatise by Daria Voropai, MD and Annebeth Kroeskop, MD in 20236 provides a pathway for the use of CaHA to combat facial aging, summarizing the rationale, approaches and techniques for using the product in the younger adult population. The article states that, “Judging on the four pillars of skin quality: evenness in tone and surface, glow and firmness, the effects in young adult patients are observed much quicker than in more mature patients (<40 years old) and last longer (author’s observation).” The point being that one can intervene earlier in the aging curve.

RA is a complex process at every level, and the goal is always to harness the body’s restorative potential. Radiesse provides an immediate filler effect when injected, directly stimulating fibroblasts and inducing synthesis of Collagen types I and III as well as increasing elastin and proteoglycans; this maintains the filler effect over time. The formation of the scaffold has low inflammatory potential. Angiogenesis provides microvascular support to the new tissue. Additionally, the rheological properties of the injectable are also robust. Thus, Radiesse is a fundamental tool in the box and a go-to for applying the principles of RA in your practice.


  1. Goldie K. The evolving field of regenerative aesthetics. J Cosmet Dermatol 2023;22(Suppl 1):1-7.
  2. Aguilera SB, McCarthy A, Khalifian S, Lorenc ZP, Goldie K, Chernoff WG. The role of calcium hydroxylapatite (Radiesse) as a regenerative aesthetic treatment: A narrative review. Aesthet Surg J 2023;43(10):1063–1090.
  3. Nowag B, Schäfer D, Hengl T, Corduff N, Goldie K. Biostimulating fillers and induction of inflammatory pathways: A preclinical investigation of macrophage response to calcium hydroxylapatite and poly-L lactic acid. J Cosmet Dermatol 2023;00:1-8.
  4. Corduff N. Introducing aesthetic regenerative scaffolds: An immunological perspective. J Cosmet Dermatol 2023;22(Suppl1):8-14.
  5. Amiri M, Meçani R, Niehot CD, et al. Skin regeneration-related mechanisms of Calcium Hydroxylapatite (CaHA): a systematic review. Frontiers in Medicine 2023;10:1-16.
  6. Voropai D, Kroeskop A. Catching the aging curve early. J Cosmet Dermatol 2023;22(Suppl 1):28-31.



RADIESSE® & RADIESSE® (+) NLF/Jawline/Hands Professional Full ISI


RADIESSE® and RADIESSE® (+) Injectable Implants are FDA-approved for subdermal implantation for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds. RADIESSE® is also indicated for hand augmentation to correct volume loss in the dorsum of the hands. Radiesse (+) injectable implant is also indicated for deep injection (subdermal and/or supraperiosteal) for soft tissue augmentation to improve moderate to severe loss of jawline contour in adults over the age of 21.



These products are contraindicated for patients with severe allergies manifested by a history of anaphylaxis, or history or presence of multiple severe allergies; patients with known hypersensitivity to any of the components; and patients with bleeding disorders. RADIESSE® (+) is contraindicated in patients with known hypersensitivity to lidocaine or anesthetics of the amide type.


Introduction of the product into the vasculature may lead to embolization, occlusion of the vessels, ischemia, or infarction. Take extra care when injecting soft tissue fillers, for example inject the product slowly and apply the least amount of pressure necessary. Rare but serious adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage, leading to stroke, skin necrosis, and damage to underlying facial structures. Immediately stop the injection if a patient exhibits any of the following symptoms, including changes in vision, signs of a stroke, blanching of the skin, or unusual pain during or shortly after the procedure. The treating physician should be knowledgeable regarding any pretreatment evaluation and appropriate interventions in the event of intravascular disseminated injection. Prompt intervention by an appropriate medical specialist should be given should these signs or symptoms of intravascular injection occur.

Use of these products in any person with active skin inflammation or infection in or near the treatment should be deferred until the inflammatory or infectious process is controlled.

Do not overcorrect (overfill) a contour deficiency with these products.

Injection into the dorsum of the hand may cause adverse events that last for more than 14 days, and may result in temporary difficulty performing activities (48% of study patients reported this adverse event). RADIESSE® may cause nodules, bumps or lumps in the dorsum of the hand (12% reported this event) and can last up to 1 year.

The safety and effectiveness for use in the lips has not been established. There have been published reports of nodules associated with the use of these products injected into the lips.


In order to minimize the risk of potential complications, this product should only be used by healthcare practitioners who have appropriate training, experience and who are knowledgeable about the anatomy at and around the injection site. Healthcare practitioners should fully familiarize themselves with the product, the product educational materials and the entire package insert.

The safety and effectiveness of RADIESSE® or RADIESSE® (+) in the following situations has not been established:

• Beyond 3 years in the face and 1 year in the hand

• In the periorbital area • Interactions between RADIESSE® or RADIESSE® (+) and drugs or other substances or implants

• Use during pregnancy, or in breastfeeding women • In the face in patients under 18 years of age • In the dorsum of the hand in patients under 26 years old and over 79 years old

• In patients with increased susceptibility to keloid formation and hypertrophic scarring

• With concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical, or chemical peeling procedures

These products contain calcium hydroxylapatite (CaHA) particles that are radiopaque and are clearly visible on CT Scans and may be visible in standard, plain radiography.

As with all transcutaneous procedures, injection of these products carries a risk of infection.

Injection in the jawline may temporarily alter jaw function.

Use of RADIESSE® in the dorsum of the hand may result in significant swelling of the dorsum of the hand.

To help avoid needle breakage, do not attempt to straighten a bent needle or cannula. Discard it and complete the procedure with a replacement needle.

Patients who are using medications that can prolong bleeding, such as aspirin or warfarin, may experience increased bruising or bleeding at the injection site.

Patients with a history of previous herpetic eruption may experience reactivation of the herpes.

Patients should minimize strenuous activity and exposure of the treated area to extensive sun or heat exposure for approximately 24 hours after treatment or until any initial swelling and redness has resolved.

Adverse Events:

Common adverse events observed in clinical studies of RADIESSE® or RADIESSE® (+) include bruising, redness, swelling, pain, itching, lumps/bumps at site of injection, difficulty chewing and other local side effects.

Cases of delayed-onset inflammation have been reported to occur at the dermal filler treatment site following viral or bacterial illnesses or infections, vaccinations, or dental procedures. Typically, the reported inflammation was responsive to treatment or resolved on its own.

Information on adverse events from post-market surveillance of RADIESSE® and RADIESSE® (+) are included in the Instructions for Use (IFU) and Patient Information Guide (PIG) based on an assessment of seriousness and potential causal relationship to RADIESSE® or RADIESSE® (+). Please see the IFU and PIG available at for a complete list of these events.

To report a problem with RADIESSE® or RADIESSE® (+), please call MyMerz Solutions at 1-844-469-6379.

For complete Safety Information please refer to the Instructions for Use at

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