Direct comparison of molecular effects of PLLA-SCA and CaHA-R in a standardized human 3D skin model containing macrophages

Summary: Abstract Body: Modern bio-stimulatory fillers like poly-L-lactic acid (PLLA-SCA; Sculptra) and calcium hydroxylapatite (CaHA-R; Radiesse) induce the synthesis of major structural components of the extracellular matrix such as collagen. However, the underlying molecular mechanisms are not yet fully understood. In a previous study we revealed that PLLA-SCA-induced collagen production in fibroblasts depends on their interaction with macrophages. The aim of the present study was to directly compare the molecular effects of PLLA-SCA and CaHA-R utilizing a previously established standardized human in vitro macrophage-containing 3D skin model. According to the clinical manual, both fillers were injected once into the dermal equivalent of the skin model. Histological analysis showed a significant increase in epidermal thickness on days 7, 14, and 21 after injection of both fillers compared to untreated controls. Next generation sequencing analysis showed a similar gene expression pattern on days 7 and 21 after injection of both fillers compared to untreated controls. While these data suggested that both fillers stimulate almost the same molecular signaling pathways, a direct comparison revealed an upregulation of members of the late cornified envelope (LCE) family at day 21 post-injection of PLLA-SCA compared to CaHA-R. In a next step, we investigated the direct effects of both fillers on collagen synthesis using immunohistochemical analysis (collagen I). While the injection of both fillers increased collagen production after 21 days, PLLA-SCA induced a significant increase in collagen synthesis already on day 7 after injection. Our data provide novel molecular insights into the bio-stimulatory effects of PLLA-SCA and CaHA-R on collagen production using 3D skin models comprising macrophages. Due to their special properties, these new in vitro models could also be used in future for research into fibrosing skin disorders. Sebastian Huth², Laura Huth¹, Yvonne Marquardt¹, Matthias Bartneck², Jens M. Baron¹ 1. Dermatology and Allergology, Universitatsklinikum Aachen, Aachen, NRW, Germany. 2. Department of Internal Medicine III, Universitatsklinikum Aachen, Aachen, NRW, Germany. Epidermal Structure and Barrier Function