Human Histology and Persistence of Various Injectable Filler Substances for Soft Tissue Augmentation

Abstract

Abstract. An increasing number of soft tissue filler substances have been introduced to the beauty market outside the U.S. which lack experimental and clinical data in support of their claim. Ten commercially available filler substances were examined for biocompatibility and durability: 0.1 cc of each substance was injected deep intradermally into the volar forearm of one of the authors and observed for clinical reaction and permanence. At 1, 3, 6, and 9 months the test sites were excised, histologically examined, and graded according to foreign body reactions classification. Collagen (Zyplast) was phagocytosed at 6 months and hyaluronic acid (Restylane) at 9 months. PMMA microspheres (Artecoll) had encapsulated with connective tissue, macrophages, and sporadic giant cells. Silicone oil (PMS 350) was clinically inconspicuous but dissipated into the tissue, causing a chronic foreign body reaction. Polylactic acid microspheres (New-Fill) induced a mild inflammatory response and had disappeared clinically at 4 months. Dextran microspheres (Reviderm intra) induced a pronounced foreign body reaction and had disappeared at 6 months. Polymethylacrylate particles (Dermalive) induced the lowest cellular reaction but had disappeared clinically at 6 months. Polyacrylamide (Aquamid) was well tolerated and remained palpable to a lessening degree over the entire testing period. Histologically, it dissipated more slowly and was kept in place through fine fibrous capsules. Polyvinylhydroxide microspheres suspended in acrylamide (Evolution) were well tolerated, slowly diminishing over 9 months. Calcium hydroxylapatite microspheres (Radiance FN) induced almost no foreign body reaction but were absorbed by the skin at 12 months.Host defense mechanisms react differently to the various filler materials, but all substances-resorbable or nonresorbable-appeared to be clinically and histologically safe, although all exhibit undesirable side effects. Since the mechanism of late inflammation or granuloma formation is still unknown, early histological findings are not useful in predicting possible late reactions to filler substances.

Lip Augmentation Dermal Filler Reactions, Histopathologic Features

“…Table 4 compares and contrasts foreign body features as well as host response reactions. Natural fillers such as collagen and hyaluronic acid, as evidenced in animal studies, are resorbed by macrophages and/or giant cells with progressive elimination of the material that will result in clinically observable shrinkage over time [1]. Why some patients react with an exuberant increase in size and nodular granuloma formation is unknown yet probably involves numerous variables such as continued trauma, rubbing or irritation, iatrogenic factors, infection, immunogenic mechanisms from protein contaminants or genetic and molecular variations in host response.…”

“…The histology in these studies mirrors that seen in case reports that clinically manifest as plaques or nodules. In those that become tumefactive, the host response is prominent although the structural features of the filler materials themselves are the same as those encountered in animal and human research models [1][2][3]. We have classified the host response in these patients as: Foreign material without inflammatory reaction (FM1), Foreign nodule with nonspecific inflammation (FN2), Foreign body granuloma with epithelioid histiocytic/multinucleated giant cell response (FBG 3).…”

“…Inert injectable biological and synthetic polymers can be precisely placed in the dermis in order to increase soft tissue bulk, produce esthetic contours and flatten wrinkles. Prior to release and marketing, these dermal fillers had been tested in animal models to ensure tissue compatibility [1,2]. Subcutaneous injection with time lapse tissue sampling and subsequent histopathologic evaluation among human volunteer subjects has also been undertaken [3].…”

“…The natural/biologic injection fillers are ultimately resorbable and therefore temporary, requiring repeated treatments to maintain desired esthetic results. Many synthetic polymers are not easily phagocytized, remain in situ with minimal resorption for many years, and are therefore considered to be permanent [1,4].…”

Lip Nodules Caused by Hyaluronic Acid Filler Injection: Report of Three Cases

“…HA is an inert and non-immunogenic filler and is usually resorbed within 4-6 months with no evidence of filler at nine months [19,36]. However, a few cases of hypersensitivity and foreign body reaction have been documented, usually developing within 6-24 months [5][6][7][8][9][10][11][12][13][14][15]35].…”