Molecular Insights Into the Effects of PLLA-SCA on Gene Expression and Collagen Synthesis in Human 3D Skin Models Containing Macrophages

J Drugs Dermatol. 2024 Apr 1;23(4):285-288. doi: 10.36849/JDD.7791.ABSTRACTInjectable poly-L-lactic acid (PLLA-SCA) is used for the correction of shallow to deep nasolabial fold contour deficiencies, cheek wrinkles, and other facial wrinkles. In contrast to hyaluronan (HA) fillers, PLLA-SCA has a biostimulatory effect by activating resident fibroblasts to produce collagen, but the mechanisms are not known in detail at the molecular level. Therefore, our aim was to investigate the molecular effects of PLLA-SCA in a comprehensive in vitro study. Since PLLA-SCA-dependent collagen production in fibroblasts depends on the interaction with macrophages, we generated novel macrophage-containing 3D skin models. According to the clinical application, PLLA-SCA was injected once into the dermal equivalent of the 3D skin model. Histological analysis showed a significant increase in epidermal thickness in these models after 5 and 14 days. Gene expression profiling revealed an upregulation of integrins and laminins (e.g., LAMA3, ITGA6), which are essential components of the dermal-epidermal junction. In addition, we found an upregulation of cytokines and chemokines (TGFB2, CXCL6, IL1B) at day 14 after PLLA-SCA injection. Interestingly, immunohistochemical analyses exhibited a significantly stimulated collagen I production in our models. These effects might be attributed, at least in part, to the upregulation of IL1B and subsequently CXCL6, which stimulates collagen I synthesis in human derm...

Source: Journal of Drugs in Dermatology - April 2, 2024 Category: Dermatology Authors: Sebastian Huth Laura Huth Yvonne Marquardt Manuela Jansen Cheng Lin Matthias Bartneck Jens Malte Baron Source Type: research