The role of bone tissue engineering in the field of regenerative medicine has been a main research topic over the past few years. There has been much interest in the use of three-dimensional (3D) engineered scaffolds (PLA) complexed with human gingival mesenchymal stem cells (hGMSCs) as a new therapeutic strategy to improve bone tissue regeneration. These devices can mimic a more favorable endogenous microenvironment for cells in vivo by providing 3D substrates which are able to support cell survival, proliferation and differentiation. The present study evaluated the in vitro and in vivo capability of bone defect regeneration of 3D PLA, hGMSCs, extracellular vesicles (EVs), or polyethyleneimine (PEI)-engineered EVs (PEI-EVs) in the following experimental groups: 3D-PLA, 3D-PLA + hGMSCs, 3D-PLA + EVs, 3D-PLA + EVs + hGMSCs, 3D-PLA + PEI-EVs, 3D-PLA + PEI-EVs + hGMSCs. The structural parameters of the scaffold were evaluated using both scanning electron microscopy and nondestructive microcomputed tomography. Nanotopographic surface features were investigated by means of atomic force microscopy. Scaffolds showed a statistically significant mass loss along the 112-day evaluation. Our in vitro results revealed that both 3D-PLA + EVs + hGMSCs and 3D-PLA + PEI-EVs + hGMSCs showed no cytotoxicity. However, 3D-PLA + PEI-EVs + hGMSCs exhibited greater osteogenic inductivity as revealed by morphological evaluation and transcriptomic analysis performed by next-generation sequencing (NGS). In addition, in vivo results showed that 3D-PLA + PEI-EVs + hGMSCs and 3D-PLA + PEI-EVs scaffolds implanted in rats subjected to cortical calvaria bone tissue damage were able to improve bone healing by showing better osteogenic properties. These results were supported also by computed tomography evaluation that revealed the repair of bone calvaria damage. The re-establishing of the integrity of the bone lesions could be a promising strategy in the treatment of accidental or surgery trauma, especially for cranial bones.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and that play an important role in many cellular processes, including modulation of inflammation. MiRNAs are present in high concentrations in the central nervous system (CNS) and are spatially and temporally expressed in a specific way. Therefore, an imbalance in the expression pattern of these small molecules can be involved in the development of neurological diseases. Generally, CNS responds to damage or disease through the activation of an inflammatory response, but many neurological disorders are characterized by uncontrolled neuroinflammation. Many studies support the involvement of miRNAs in the activation or inhibition of inflammatory signaling and in the promotion of uncontrolled neuroinflammation with pathological consequences. MiR-155 is a pro-inflammatory mediator of the CNS and plays an important regulatory role. The purpose of this review is to summarize how miR-155 is regulated and the pathological consequences of its deregulation during neuroinflammatory disorders, including multiple sclerosis, Alzheimer’s disease and other neuroinflammatory disorders. Modulation of miRNAs’ expression could be used as a therapeutic strategy in the treatment of pathological neuroinflammation.

Alzheimer’s disease (AD) is a neurodegenerative disorder representing the major cause of dementia. It is characterized by memory loss, and cognitive and behavioral decline. In particular, the hallmarks of the pathology are amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), formed by aggregated hyperphosphorylated tau protein. Oxidative stress plays a main role in AD, and it is involved in initiation and progression of AD. It is well known that Aβ induced oxidative stress, promoting reactive oxygen species (ROS) production and consequently lipid peroxidation, protein oxidation, tau hyperphosphorylation, results in toxic effects on synapses and neurons. In turn, oxidative stress can increase Aβ production. For these reasons, the administration of an antioxidant therapy in AD patients was suggested. The term vitamin E includes different fat-soluble compounds, divided into tocopherols and tocotrienols, that possess antioxidant action. α-Tocopherol is the most studied, but some studies suggested that tocotrienols may have different health promoting capacities. In this review, we focused our attention on the effects of vitamin E supplementation in AD animal models and AD patients or older population. Experimental models showed that vitamin E supplementation, by decreasing oxidative stress, may be a good strategy to improve cognitive and memory deficits. Furthermore, the combination of vitamin E with other antioxidant or anti-inflammatory compounds may increase its efficacy. However, even if some trials have evidenced some benefits, the effects of vitamin E in AD patients are still under debate.

Inflammation and oxidative stress play main roles in neurodegeneration. Interestingly, different natural compounds may be able to exert neuroprotective actions against inflammation and oxidative stress, protecting from neuronal cell loss. Among these natural sources, Cannabis sativa represents a reservoir of compounds exerting beneficial properties, including cannabigerol (CBG), whose antioxidant properties have already been demonstrated in macrophages. Here, we aimed to evaluate the ability of CBG to protect NSC-34 motor neurons against the toxicity induced from the medium of LPS-stimulated RAW 264.7 macrophages. Using MTT assay, we observed that CBG pre-treatment was able to reduce the loss of cell viability induced by the medium of LPS-stimulated macrophages in NSC-34 cells. Indeed, CBG pre-treatment inhibited apoptosis, as shown by the reduction of caspase 3 activation and Bax expression, while Bcl-2 levels increased. Furthermore, CBG pre-treatment counteracted not only inflammation, as demonstrated by the reduction of IL-1β, TNF-α, IFN-γ and PPARγ protein levels assessed by immunocytochemistry, but also oxidative stress in NSC-34 cells treated with the medium of LPS-stimulated RAW 264.7. Indeed, immunocytochemistry showed that CBG pre-treatment reduced nitrotyrosine, SOD1 and iNOS protein levels and restored Nrf-2 levels. All together, these results indicated the neuroprotective effects of CBG, that may be a potential treatment against neuroinflammation and oxidative stress.

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.

Purpose: The combination of oral derived stem cells and 3-D scaffolds is considered advantageous in bone repair. In particular, collagen membranes possess ideal biological properties and can support infiltration and proliferation of osteoblasts, promoting bone regeneration. Our study aimed to develop a new biocompatible osteogenic construct composed of a commercially available collagen membrane (Evolution [Evo]), human periodontal-ligament stem cells (hPDLSCs) enriched with extracellular vesicles (EVs), or polyethylenimine (PEI)-engineered EVs (PEI-EVs). Methods: Osteogenic ability and expression of osteogenic genes were evaluated in vitro in hPDLSCs cultured with or without Evo, with Evo and EVs, or PEI-EVs. In addition, the bone-regeneration capacity of Evo, Evo enriched with hPDLSCs, Evo enriched with hPDLSCs and EVs/PEI-EVs was investigated in rats subjected to calvarial defects. Results: Our results showed that Evo enriched with EVs and PEI-EVs showed high biocompatibility and osteogenic properties in vitro and in vivo. In addition, quantitative reverse-transcription polymerase chain reaction demonstrated the upregulation of osteogenic genes, such as TGFB1, MMP8, TUFT1, TFIP11, BMP2, and BMP4, in the presence of PEI-EVs. Upregulation of BMP2/4 was confirmed for Evo enriched with PEI-EVs and hPDLSCs both in vitro by Western blot and in vivo by immunofluorescence. Conclusion: Our results indicated that Evo enriched with hPDLSCs and PEI-EVs is able to promote a bone-regeneration process for the treatment of calvarium and ossification defects caused by accidental or surgery trauma. In particular, PEI-EVs had a significant role in activation of the osteogenic process.