Common in ageing patient, the solar lentigo is a macular hyperpigmented skin lesion that results from chronic exposure to ultraviolet irradiations. Despite sharing numerous features with other pigmented spots, the diagnostic of this benign lesion is well characterized at the tissue level. Recent studies shed lights on several factors and their pathogenic mechanisms involved in the development of the solar lentigo. This review summarizes how diverse experimental approaches allowed the identification of several biomarkers, which contribute to a better understanding on the initiation and the maintenance of this pigmentary disorder.
Keloid refers to a fibroproliferative disorder characterized by an accumulation of extracellular matrix (ECM) components at the dermis level, overgrowth beyond initial wound, and formation of tumor-like nodule areas. Treating keloid is still an unmet clinical need and the lack of an efficient therapy is clearly related to limited knowledge about keloid etiology, despite the growing interest of the scientific community in this pathology. In past decades, keloids were often studied in vitro through the sole prism of fibroblasts considered as the major effector of ECM deposition. Nevertheless, development of keloids results from cross-interactions of keloid fibroblasts (KFs) and their surrounding microenvironment, including immune cells such as macrophages. Our study aimed to evaluate the effect of M1 and M2 monocyte-derived macrophages on KFs in vitro. We focused on the effects of the macrophage secretome on fibrosis-related criteria in KFs, including proliferation, migration, differentiation, and ECM synthesis. First, we demonstrated that M2-like macrophages enhanced the fibrogenic profile of KFs in culture. Then, we surprisingly founded that M1-like macrophages can have an anti-fibrogenic effect on KFs, even in a pro-fibrotic environment. These results demonstrate, for the first time, that M1 and M2 macrophage subsets differentially impact the fibrotic fate of KFs in vitro, and suggest that restoring the M1/M2 balance to favor M1 in keloids could be an efficient therapeutic lever to prevent or treat keloid fibrosis.
22 January 2018 in Journal of Cosmetic Dermatology
Tailored porous structures of poly(2-hydroxyethyl methacrylate) (PHEMA) and silk sericin (SS) were used to create porous hydrogel scaffolds using two distinct crosslinking systems. These structures were designed to closely mimic the porous nature of the native extracellular matrix. Conventional free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) was performed in the presence of different concentrations of SS (1.25, 2.50, 5.00% w/v) with two crosslinking systems. A chemical crosslinking system with N’N-methylene bisacrylamide (MBAAm) and a physical crosslinking system with dimethylurea (DMU) were used: C-PHEMA/SS (crosslinked using MBAAm) and C-PHEMA/pC-SS (crosslinked using MBAAm and DMU). The focus of this study was on investigating the impact of these crosslinking methods on various properties of the scaffolds, including pore size, pore characteristics, polymerization time, morphology, molecular interaction, in vitro degradation, thermal properties, and in vitro cytotoxicity. The various crosslinked networks were found to appreciably influence the properties of the scaffolds, especially the pore sizes, in which smaller sizes and higher numbers of pores with high regularity were seen in C-PHEMA/1.25 pC-SS (17 ± 2 μm) than in C-PHEMA/1.25 SS (34 ± 3 μm). Semi-interpenetrating networks were created by crosslinking PHEMA-MBAAm-PHEMA while incorporating free protein molecules of SS within the networks. The additional crosslinking step involving DMU occurred through hydrogen bonding of the -C=O and -N-H groups with the SS, resulting in the simultaneous incorporation of DMU and SS within the PHEMA networks. As a consequence of this process, the scaffold C-PHEMA/pC-SS exhibited smaller pore sizes compared to scaffolds without DMU crosslinking. Moreover, the incorporation of higher loadings of SS led to even smaller pore sizes. Additionally, the gelation time of C-PHEMA/pC-SS was delayed due to the presence of DMU in the crosslinking system. Both porous hydrogel scaffolds, C-PHEMA/pC-SS and PHEMA, were found to be non-cytotoxic to the normal human skin dermal fibroblast cell line (NHDF cells). This promising result indicates that these hydrogel scaffolds have potential for use in tissue engineering applications.