: For decades, a wide variety of natural and synthetic materials have been used to augment human tissue to improve aesthetic outcomes. Dermal fillers are some of the most widely used aesthetic treatments throughout the body. Initially, the primary function of dermal fillers was to restore depleted volume. As biomaterial research has advanced, however, a variety of biostimulatory fillers have become staples in aesthetic medicine. Such fillers often contain a carrying vehicle and a biostimulatory material that induces de novo synthesis of major structural components of the extracellular matrix. One such filler, Radiesse (Merz Aesthetics, Raleigh, NC), is composed of calcium hydroxylapatite microspheres suspended in a carboxymethylcellulose gel. In addition to immediate volumization, Radiesse treatment results in increases of collagen, elastin, vasculature, proteoglycans, and fibroblast populations via a cell-biomaterial–mediated interaction. When injected, Radiesse acts as a cell scaffold and clinically manifests as immediate restoration of depleted volume, improvements in skin quality and appearance, and regeneration of endogenous extracellular matrices. This narrative review contextualizes Radiesse as a regenerative aesthetic treatment, summarizes its unique use cases, reviews its rheological, material, and regenerative properties, and hypothesizes future combination treatments in the age of regenerative aesthetics. Level of Evidence: 5:

Biomaterials without incorporating therapeutic agents and living cells effectively repair critical-sized rat cranial bone defects.

Injectable fillers, pivotal in aesthetic medicine, have evolved significantly with recent trends favoring biostimulators like calcium hydroxylapatite (CaHA‐CMC; Radiesse, Merz Aesthetics, Raleigh, NC) and poly‐ l ‐lactic acid (PLLA; Sculptra Aesthetics, Galderma, Dallas, TX). This study aims to compare the particle morphology of these two injectables and examine its potential clinical implications. Utilizing advanced light and scanning electron microscopy techniques, the physical characteristics of CaHA‐CMC and PLLA particles were analyzed, including shape, size, circularity, roundness, aspect ratio, and quantity of phagocytosable particles. The findings reveal several morphological contrasts: CaHA‐CMC particles exhibited a smooth, homogenous, spherical morphology with diameters predominantly ranging between 20 and 45 µm, while PLLA particles varied considerably in shape and size, appearing as micro flakes ranging from 2 to 150 µm in major axis length. The circularity and roundness of CaHA‐CMC particles were significantly higher compared to PLLA, indicating a more uniform shape. Aspect ratio analysis further underscored these differences, with CaHA‐CMC particles showing a closer resemblance to circles, unlike the more oblong PLLA particles. Quantification of the phagocytosable content of both injectables revealed a higher percentage of phagocytosable particles in PLLA. These morphological distinctions may influence the tissue response to each treatment. CaHA‐CMC's uniform, spherical particles may result in reduced inflammatory cell recruitment, whereas PLLA's heterogeneous particle morphology may evoke a more pronounced inflammatory response.

Background: Calcium hydroxylapatite‐carboxymethylcellulose (CaHA‐CMC) injectables have emerged as dual‐purpose fillers with bioregenerative and direct filling capabilities.Aims: This study investigates the rheological properties of CaHA‐CMC and its CMC carrier gel at various dilutions.Methods: The storage modulus (G′), loss modulus (G″), complex viscosity (η*), loss factor (tan δ), cohesivity, and extrusion force were evaluated for a range of CaHA‐CMC aqueous dilutions with an oscillatory rheometer, drop weight testing, and force analysis, respectively.Results: Results revealed a significant decrease in G′, η*, and increase in tan(δ) with increasing dilution, indicating a decline in the product's direct filling capabilities. Cohesivity decreased dramatically with dilution, potentially enhancing tissue biointegration and the product's biostimulatory effects. The CMC gel carrier displayed inelastic and non‐resilient properties, with rheological changes differing from CaHA‐CMC. Dilutional rheology was also correlated with previously published dilution‐dependent biostimulatory data where hyperdiluted CaHA‐CMC (>1:2) demonstrated a regenerative profile and diluted or hypodiluted mixtures retained meaningful filling properties and increased regeneration.Conclusions: These findings offer a continuum for tailoring the product's rheological profile to match specific tissue requirements. Customizable rheology allows CaHA‐CMC to be tuned for either filling and contouring or optimal regenerative effects. Importantly, safety implications related to vascular occlusion suggest that dilutional rheomodulation decreases the risk of vascular events. In conclusion, this study highlights the significant impact of aqueous dilution on the rheological properties of CaHA‐CMC and its carrier gel. The findings support the clinical application of tailored dilutions to achieve desired outcomes, providing versatility and safety for aesthetic applications.