The epithelial–mesenchymal transition (EMT) is an essential event during cell development, in which epithelial cells acquire mesenchymal fibroblast-like features including reduced intercellular adhesion and increased motility. EMT also plays a key role in wound healing processes, which are mediated by inflammatory cells and fibroblasts. These cells secrete specific factors that interact with molecules of the extracellular matrix (ECM) such as collagens, laminins, elastin and tenascins. Wound healing follows four distinct and successive phases characterized by haemostasis, inflammation, cell proliferation and finally tissue remodeling. EMT is classified into three diverse subtypes: type-1 EMT, type-2 EMT and type-3 EMT. Type-1 EMT is involved in embryogenesis and organ development. Type-2 EMT is associated with wound healing, tissue regeneration and organ fibrosis. During organ fibrosis, type-2 EMT occurs as a reparative-associated process in response to ongoing inflammation and eventually leads to organ destruction. Type-3 EMT is implicated in cancer progression, which is linked to the occurrence of genetic and epigenetic alterations, in detail the ones promoting clonal outgrowth and the formation of localized tumors. The current review aimed at exploring the role of EMT process with particular focus on type-2 EMT in wound healing, fibrosis and tissue regeneration, as well as some recent progresses in the EMT and tissue regeneration field, including the modulation of EMT by biomaterials.

Bone tissue renewal can be outlined as a complicated mechanism centered on the interaction between osteogenic and angiogenic events capable of leading to bone formation and tissue renovation. The achievement or debacle of bone regeneration is focused on the primary role of vascularization occurrence; in particular, the turning point is the opportunity to vascularize the bulk scaffolds, in order to deliver enough nutrients, growth factors, minerals and oxygen for tissue restoration. The optimal scaffolds should ensure the development of vascular networks to warrant a positive suitable microenvironment for tissue engineering and renewal. Vascular Endothelial Growth Factor (VEGF), a main player in angiogenesis, is capable of provoking the migration and proliferation of endothelial cells and indirectly stimulating osteogenesis, through the regulation of the osteogenic growth factors released and through paracrine signaling. For this reason, we concentrated our attention on two principal groups involved in the renewal of bone tissue defects: the cells and the scaffold that should guarantee an effective vascularization process. The application of Mesenchymal Stem Cells (MSCs), an excellent cell source for tissue restoration, evidences a crucial role in tissue engineering and bone development strategies. This review aims to provide an overview of the intimate connection between blood vessels and bone formation that appear during bone regeneration when MSCs, their secretome—Extracellular Vesicles (EVs) and microRNAs (miRNAs) —and bone substitutes are used in combination.

In the last few decades, tissue engineering has become one of the most studied medical fields. Even if bone shows self-remodeling properties, in some cases, due to injuries or anomalies, bone regeneration can be required. In particular, oral bone regeneration is needed in the dentistry field, where the functional restoration of tissues near the tooth represents a limit for many dental implants. In this context, the application of biomaterials and mesenchymal stem cells (MSCs) appears promising for bone regeneration. This review focused on in vivo studies that evaluated bone regeneration using biomaterials with MSCs. Different biocompatible biomaterials were enriched with MSCs from different sources. These constructs showed an enhanced bone regenerative power in in vivo models. However, we discussed also a future perspective in tissue engineering using the MSC secretome, namely the conditioned medium and extracellular vesicles. This new approach has already shown promising results for bone tissue regeneration in experimental models.

Tissue engineering and/or regenerative medicine are fields of life science exploiting both engineering and biological fundamentals to originate new tissues and organs and to induce the regeneration of damaged or diseased tissues and organs. In particular, de novo bone tissue regeneration requires a mechanically competent osteo-conductive/inductive 3D biomaterial scaffold that guarantees the cell adhesion, proliferation, angiogenesis and differentiation into osteogenic lineage. Cellular components represent a key factor in tissue engineering and bone growth strategies take advantage from employment of mesenchymal stem cells (MSCs), an ideal cell source for tissue repair. Recently, the application of extracellular vesicles (EVs), isolated from stem cells, as cell-free therapy has emerged as a promising therapeutic strategy. This review aims at summarizing the recent and representative research on the bone tissue engineering field using a 3D scaffold enriched with human oral stem cells and their derivatives, EVs, as a promising therapeutic potential in the reconstructing of bone tissue defects.

The level of environmental microplastics in the sea is constantly increasing. They can enter the human body with food, be absorbed through the gut and have negative effects on the organism’s health after its digestion. To date, microplastics (MPs) are considered new environmental pollutants in the air sea and they are attracting wide attention. The possible toxic effects of MPs isolated at different sea depths of 1, 24 and 78 m were explored in an in vitro model of human gingival fibroblasts (hGFs). MPs isolated from the sea showed different size and were then divided into different sample groups: 1, 24 and 78 m. The results obtained revealed that MPs are able to activate the inflammatory pathway NFkB/MyD88/NLRP3. In detail, the exposure to MPs from 1 and 78 m led to increased levels of inflammatory markers NFkB, MyD88 and NLRP3 in terms of proteins and gene expression. Moreover, cells exposed to MPs showed a lower metabolic activity rate compared to unexposed cells. In conclusion, these findings demonstrate that the inflammation process is stimulated by MPs exposure, providing a new perspective to better understand the intracellular mechanism.

Resin (co)monomers issued from restorative dental materials are able to distribute in the dental pulp or the gingiva, to get to the saliva and to the flowing blood. Many authors have recently shown that methacrylate-based resins, in particular 2-hydroxyethylmethacrylate (HEMA), are responsible of inflammatory and autophagic processes in human dental pulp stem cells (hDPSCs) while ascorbic acid (AS), an antioxidant molecule, can assume a protective role in cell homeostasis. The purpose of the current work was to study if 50 µg/mL AS can affect the inflammatory status induced by 2 mM HEMA in hDPSCs, a tissue–specific cell population. Cell proliferation, cytokine release, morphological arrangement and reactive oxygen species (ROS) formation were determined respectively by MTT, ELISA, morphological analysis and dichlorofluorescein assay. The hDPSCs exposed to HEMA let to an increment of ROS formation and in the expression of high levels of inflammatory mediators such as nuclear factor-κB (NFkB), inflammatory cytokines such as interleukin IL6, IL8, interferon (IFN)ɣ and monocyte chemoattractant protein (MCP)1. Moreover, HEMA induced the up-regulation of pospho-extracellular signal–regulated kinases (pERK)/ERK signaling pathway associated to the nuclear translocation. AS treatment significantly down-regulated the levels of pro-inflammatory mediators. Then, the natural product AS reduced the detrimental result promoted by methacrylates in clinical dentistry, in fact restore cell proliferation, reduce the pro-inflammatory cytokine, downregulate ROS production and of NFkB/pERK/ERK signaling path. In synthesis, AS, could improve the quality of dental care and play a strategic role as innovative endodontic compound easy to use and with reasonable cost.