Comparison of Physicochemical Characteristics and Biostimulatory Functions in Two Calcium Hydroxyapatite-Based Dermal Fillers

September 2023 | Volume 22 | Issue 9 | 910 | Copyright © September 2023


Published online August 28, 2023

Cleiton Kunzler PhDa, Christian Hartmann PhDb, Bartosch Nowag PhDb, Riddhi Shah PhDc, Radia El-Banna a, Sarah Backfisch a, Daniela Schafer b, Thomas Hengl PhDb, Nadine Hagedorn a

aR&D Filler and Medical Device Development Department, Merz Aesthetics GmbH, Frankfurt am Main, Germany
bR&D Skin Lab & Nonclinical Science Department, Merz Aesthetics GmbH, Frankfurt am Main, Germany
cGlobal Clinical R&D, Merz North America, Inc., Raleigh, NC

Abstract
Background:  Dermal fillers containing calcium hydroxyapatite (CaHA) are categorized as biostimulatory. However, differences in CaHA biomaterial likely affect the resultant induction of collagen synthesis, and variability in microsphere shape and size likely influences a patient’s immune response. This study compares 2 CaHA based fillers: one suspended in carboxymethylcellulose (denoted "CaHA/CMC"), and one crosslinked with 1,4-butanediol diglycidyl ether to hyaluronic acid (denoted "CaHA/HA").
Objective: To characterize CaHA/CMC and CaHA/HA fillers to stimulate in vitro collagen biosynthesis.
Methods: Physicochemical evaluations included G′ and extrusion force. Scanning electron microscopy (SEM) was used to characterize isolated CaHA microspheres and freeze-dried formulations. Collagen I and III expression were evaluated using immunofluorescence.
Results: CaHA/CMC showed higher G′ (P<0.001) and lower extrusion force (P=0.0003), with uniform polymeric-matrix interactions, compared with CaHA/HA. On SEM, isolated microspheres and freeze-dried CaHA/CMC showed round and smooth surfaced microspheres of similar size. Isolated microspheres and freeze-dried CaHA/HA showed nonhomogeneous, broken microspheres, of various sizes, with fragments embedded in the polymer matrix. Although both fillers induced collagen III expression, only CaHA/CMC induced longer-lasting collagen I expression, with increases of 123% (P=0.007) and 164% (P<0.0001) at 2 and 5 mg/mL, respectively, compared with control. CaHA/CMC also increased collagen I expression at equivalent CaHA microsphere concentrations at 2 (P=0.0052) and 5 mg/mL (P<0.0001), compared with CaHA/HA.
Conclusion: The physicochemical characteristics selected for evaluation were more favorable for CaHA/CMC than CaHA/HA. When compared with CaHA/HA, the smooth, homogeneous microsphere composition of CaHA/CMC promoted significantly more collagen I biosynthesis, an essential process for tissue augmentation and long-lasting aesthetic improvement.
 
Citation: Kunzler C, Hartmann C, Nowag B, et al. Comparison of physicochemical characteristics and biostimulatory functions in two calcium hydroxyapatite-based dermal fillers. J Drugs Dermatol. 2023;22(9):910-916. doi:10.36849/JDD.7684

INTRODUCTION

Advancement in aesthetic research and technology has resulted in development of numerous cosmetic products, including dermal fillers used for soft-tissue augmentation. Such fillers provide physicians and patients ample options for various non-invasive aesthetic treatments.1,2 With ongoing development, practitioners began requesting information on product composition required to achieve the highest lift, to provide the best reduction in volume loss, and to induce optimal biostimulatory effects, for example, while also considering the patient's aesthetic condition, anatomical structure, and treatment preferences.3,4 Furthermore, different dermal fillers meet different patient and provider needs - some add volume, some fill wrinkles, folds, or other hollows, some have an immediate volumizing effect, and some require time to properly augment a particular aesthetic condition. A single product cannot be considered as most effective or superior to other products.5,6

Commonly used dermal fillers are gel-like substances consisting of either hyaluronic acid (HA) or calcium hydroxyapatite (CaHA) microspheres suspended in a fluid phase. Due to its favorable rheological properties, CaHA has been widely used for volume-loss correction and natural collagen stimulation and, most importantly, for its long-lasting effect.1,2 CaHA activates collagen, elastin formation, and angiogenesis approximately 4 to 9 months following injection;7,8 CaHA's duration ranges from 9 to 18 months, compared with HA fillers that degrade within 4 to 6 months.1,4,9
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