LAUSR

The reason for these simple tests was the lack of knowledge on the effects and reactions of surging dermal fillers in 2003. How can we as physicians inject any dermal filler not knowing what histologic reactions it causes in the dermis and beneath? What is the mechanism of its absorption, and how long does it last? Does a filler remain where it is injected, or does it dissipate in the surrounding tissue like some fluid fillers? What kind of cells are attacking or removing the different fillers, and which fillers may induce an excessive foreign body response and how can it be treated? How effective are antidots like hyaluronidase or corticosteroids in the treatment of granulomas [1], or as some call a granuloma today: a ‘late-onset inflammatory adverse reaction’? During the past two decades, we have greatly expanded our understanding and knowledge of various different fillers that are now ranging from 6 months to 5 years in efficacy with our increased understanding of each filler’s unique histologic response over time. Since our original publication in 2003 [2], I have continuously injected more than 100 blebs of different fillers beneath the dermis of my left forearm (Fig. 1). Human skin reacts differently compared to the skin of pigs, rats, or mice. For the past 35 years, tissue biocompatibility and longevity of various available fillers became the major interest of dermal filler research (Fig. 2). The finding of the most suitable carrier for micro-particulate fillers, whether bovine collagen, hyaluronic acid, carboxymethyl-cellulose, or even alginate, is an important issue in developing new fillers in the future. Human tissues remain ideal test sites for optimal concentrations of microparticles, which shall smoothly pass long catheters, which have certain diameters to prevent entering small veins, and are stimulating enough connective tissue to form ‘‘living implants’’ in the skin or ‘‘vascularized bulking agents’’. Interestingly, of the 10 tested dermal fillers commonly used in Europe back in 2003, half of them soon disappeared from the market: Zyderm and Zyplast have been displaced by Restylane and Juvederm , and fluid silicone 350, Reviderm , Dermalive , and Evolution , were causing an unacceptable rate of foreign body granulomas (Fig. 3) [1]. In 2020, Restylane remains the #1 filler globally among the approximately 150 hyaluronic acid (HA) fillers available, which slightly differ in cross-linking, and concentration. HA fillers today account for about 80% of the global filler market. On the other side of the spectrum, the permanent PMMA-collagen filler Artecoll has been widely and safely used in China since 2002, and ArteFill (now Bellafill ) has been used successfully in the U.S., and some other countries since its FDA approval in 2006 [3]. Two PMMA-microsphere-based fillers using carboxymethyl-cellulose as carrier (Linnea safe and Biosimetric ) are leading in Brazil due to their much cheaper price, PLA-based Newfill changed its name to Sculptra , which experienced its greatest success during times of more prevalent HIV-facial-dystrophy, Aquamid claims biofilm-infection for its increasing rate of foreign body granulomas, and Radiesse , formerly called Radiance , & Gottfried Lemperle [email protected]