Use of Hydrogels in Regenerative Medicine: Focus on Mechanical Properties.

Bioengineered materials represent an innovative option to support the regenerative processes of damaged tissues, with the final objective of creating a functional environment closely mimicking the native tissue. Among the different available biomaterials, hydrogels represent the solution of choice for tissue regeneration, thanks to the easy synthesis process and the highly tunable physical and mechanical properties. Moreover, hydrogels are biocompatible and biodegradable, able to integrate in biological environments and to support cellular interactions in order to restore damaged tissues' functionality.

Low ozone concentrations do not exert cytoprotective effects on tamoxifen-treated breast cancer cells .

Medical treatment with low ozone concentrations proved to exert therapeutic effects in various diseases by inducing a cytoprotective antioxidant response through the nuclear factor erythroid derived-like 2 (Nrf2) transcription factor pathway. Low ozone doses are increasingly administered to oncological patients as a complementary treatment to mitigate some adverse side-effects of antitumor treatments. However, a widespread concern exists about the possibility that the cytoprotective effect of Nrf2 activation may confer drug resistance to cancer cells or at least reduce the efficacy of antitumor agents.

Nanotechnological Research for Regenerative Medicine: The Role of Hyaluronic Acid.

Hyaluronic acid (HA) is a linear, anionic, non-sulfated glycosaminoglycan occurring in almost all body tissues and fluids of vertebrates including humans. It is a main component of the extracellular matrix and, thanks to its high water-holding capacity, plays a major role in tissue hydration and osmotic pressure maintenance, but it is also involved in cell proliferation, differentiation and migration, inflammation, immunomodulation, and angiogenesis. Based on multiple physiological effects on tissue repair and reconstruction processes, HA has found extensive application in regenerative medicine.

Modifications of Blood Molecular Components after Treatment with Low Ozone Concentrations.

The ex vivo treatment of a limited volume of blood with gaseous oxygen-ozone (O-O) mixtures and its rapid reinfusion into the patient is a widespread medical procedure. O instantly reacts with the blood's antioxidant systems, disappearing before reinfusion, although the molecules formed act as messengers in the organism, inducing multiple antioxidant and anti-inflammatory responses. An appropriate dose of O is obviously essential to ensure both safety and therapeutic efficacy, and in recent years, the low-dose O concept has led to a significant reduction in the administered O concentrations.

Evaluating the role of protective creams on the cutaneous penetration of Ni nanoparticles.

There is an increase of application of Nickel in the form of nanoparticles (NiNPs) in several fields including modern metallurgy, bioengineering, and medicine. Such growth of the areas of application is actually accompanied with an increase of exposure to Nickel, thus an intensification of the negative effects, the most frequent being the allergic contact dermatitis. Indeed, due to their smaller size, and therefore their higher surface area, NiNPs can release more Ni ions compared to bulk material, that can penetrate and permeate through the skin.

The contribution of immunohistochemistry to the development of hydrogels for skin repair and regeneration.

Hydrogels based on various polymeric materials have been successfully developed in recent years for a variety of skin applications. Several studies have shown that hydrogels with regenerative, antibacterial, and antiinflammatory properties can provide faster and better healing outcomes, particularly in chronic diseases where the normal physiological healing process is significantly hampered. Various experimental tests are typically performed to assess these materials' ability to promote angiogenesis, re-epithelialization, and the production and maturation of new extracellular matrix.

Cardiac Differentiation Promotes Focal Adhesions Assembly through Vinculin Recruitment.

Cells of the cardiovascular system are physiologically exposed to a variety of mechanical forces fundamental for both cardiac development and functions. In this context, forces generated by actomyosin networks and those transmitted through focal adhesion (FA) complexes represent the key regulators of cellular behaviors in terms of cytoskeleton dynamism, cell adhesion, migration, differentiation, and tissue organization. In this study, we investigated the involvement of FAs on cardiomyocyte differentiation.

An ex vivo experimental system to track fluorescent nanoparticles inside skeletal muscle.

The development of novel nanoconstructs for biomedical applications requires the assessment of their biodistribution, metabolism and clearance in single cells, organs and entire organisms in a living environment. To reduce the number of in vivo experiments performed and to refine the methods used, in accordance with the 3Rs principle, this work proposes an ex vivo experimental system to monitor, using fluorescence microscopy, the distribution of nanoparticles in explanted murine skeletal muscle maintained in a bioreactor that can preserve the structural and functional features of the organ for long periods of time. Fluorescently-labelled liposomes and poly(lactide-co-glycolide) (PLGA)-based nanoparticles were injected into the intact soleus muscle (in the distal region close to the tendon) immediately after explants, and their distribution was analysed at increasing incubation times in cross cryosections from the proximal region of the belly.

Assessing the interactions between nanoparticles and biological barriers in vitro: a new challenge for microscopy techniques in nanomedicine.

Nanoconstructs intended to be used as biomedical tool must be assessed for their capability to cross biological barriers. However, studying in vivo the permeability of biological barriers to nanoparticles is quite difficult due to the many structural and functional factors involved. Therefore, the in vitro modeling of biological barriers -2D cell monocultures, 2D/3D cell co-cultures, microfluidic devices- is gaining more and more relevance in nanomedical research.

Repurposing pentamidine using hyaluronic acid-based nanocarriers for skeletal muscle treatment in myotonic dystrophy.

In a context of drug repurposing, pentamidine (PTM), an FDA-approved antiparasitic drug, has been proposed to reverse the splicing defects associated in myotonic dystrophy type 1 (DM1). However, clinical use of PTM is hinder by substantial toxicity, leading to find alternative delivery strategies. In this work we proposed hyaluronic acid-based nanoparticles as a novel encapsulation strategy to efficiently deliver PTM to skeletal muscles cells.

Alcian Blue Staining to Visualize Intracellular Hyaluronic Acid-Based Nanoparticles.

Investigating at transmission electron microscopy the intracellular trafficking of hyaluronic acid-based nanoparticles remains a challenge due to their intrinsic weak electron density. Here we describe a simple protocol to stain hyaluronic acid that allows visualization of hyaluronic acid-based nanoparticles inside cells at both light and electron microscopy. By applying the critical-electrolyte-concentration Alcian blue method, these nanoparticles were observed as blue dots at bright-field microscopy or filled with fine electron dense precipitates at transmission electron microscopy.

Regenerative Potential of A Bovine ECM-Derived Hydrogel for Biomedical Applications.

Recent advancements in regenerative medicine have enhanced the development of biomaterials as multi-functional dressings, capable of accelerating wound healing and addressing the challenge of chronic wounds. Hydrogels obtained from decellularized tissues have a complex composition, comparable to the native extracellular environment, showing highly interesting characteristics for wound healing applications. In this study, a bovine pericardium decellularized extracellular matrix (dECM) hydrogel was characterized in terms of macromolecules content, and its immunomodulatory, angiogenic and wound healing potential has been evaluated.

In Vitro Models of Biological Barriers for Nanomedical Research.

Nanoconstructs developed for biomedical purposes must overcome diverse biological barriers before reaching the target where playing their therapeutic or diagnostic function. In vivo models are very complex and unsuitable to distinguish the roles plaid by the multiple biological barriers on nanoparticle biodistribution and effect; in addition, they are costly, time-consuming and subject to strict ethical regulation. For these reasons, simplified in vitro models are preferred, at least for the earlier phases of the nanoconstruct development.

Photobiomodulation induces microvesicle release in human keratinocytes: PI3 kinase-dependent pathway role.

Microvesicles (MVs, 100-1000 nm diameter) are released into the extracellular environment by mammalian cells. MVs interact with near or remote cells through different mechanisms; in particular, MVs from human keratinocytes accelerate wound healing. Photobiomodulation by laser improves wound healing, but no information is available about its effects on MV release from human keratinocyte.

Gut-Ex-Vivo system as a model to study gluten response in celiac disease.

Celiac disease (CD) is a complex immune-mediated chronic disease characterized by a consistent inflammation of the gastrointestinal tract induced by gluten intake in genetically predisposed individuals. Although initiated by the interaction between digestion-derived gliadin, a gluten component, peptides, and the intestinal epithelium, the disorder is highly complex and involving other components of the intestine, such as the immune system. Therefore, conventional model systems, mainly based on two- or three-dimension cell cultures and co-cultures, cannot fully recapitulate such a complex disease.

Nanomedicine for Gene Delivery and Drug Repurposing in the Treatment of Muscular Dystrophies.

Muscular Dystrophies (MDs) are a group of rare inherited genetic muscular pathologies encompassing a variety of clinical phenotypes, gene mutations and mechanisms of disease. MDs undergo progressive skeletal muscle degeneration causing severe health problems that lead to poor life quality, disability and premature death. There are no available therapies to counteract the causes of these diseases and conventional treatments are administered only to mitigate symptoms.

Platelet rich plasma-derived microvesicles increased in vitro wound healing.

Objective: Platelet rich plasma (PRP) is a haemoderivative used in clinical practice for the treatment of hard-to-heal wounds. Platelet (PLT) activation is a key factor in the wound healing process leading to the production of extracellular vesicles. We obtained PRP and PRP-derived microvesicles (PLT-MVs) from healthy donors and compared their pro-healing efficacy in an in vitro wound model using human keratinocytes.

[Post-traumatic stress disorder in prison].

PTSD is frequent in prison, with a lifetime prevalence of 17.8% among male inmates, and of 40.1% among female inmates.

Mental disorders on admission to jail: A study of prevalence and a comparison with a community sample in the north of France.

Background: The aim of the present study was to estimate prevalence rates of psychiatric and substance use disorders in male and female prisoners on admission to prison in the north of France and compare the frequency of these disorders to the general population.

Methods: This cross-sectional survey on Mental Health in the Prison Population (MHPP), conducted between March 2014 and April 2017, interviewed 653 randomly selected men and women who had recently been committed to the French general population prison system in the Nord and Pas-de-Calais departments. For each subject, the Mini International Neuropsychiatric Interview (MINI), a standardized psychiatric interview, was used to screen for psychiatric and substance use disorders.

Automatic segmentation of brain tumor resections in intraoperative ultrasound images using U-Net.

To compensate for the intraoperative brain tissue deformation, computer-assisted intervention methods have been used to register preoperative magnetic resonance images with intraoperative images. In order to model the deformation due to tissue resection, the resection cavity needs to be segmented in intraoperative images. We present an automatic method to segment the resection cavity in intraoperative ultrasound (iUS) images.

Alcian blue staining to track the intracellular fate of hyaluronic-acid-based nanoparticles at transmission electron microscopy.

The main step in the assessment of nanomaterial safety and suitability for biomedical use is the location and the dynamic tracking of nanoparticles (NPs) inside cells or tissues. To precisely investigate the uptake mechanisms and intracellular fate of NPs, transmission electron microscopy is the technique of choice; however, the detection of NPs may sometimes be problematic. In fact, while NPs containing strongly electron dense (e.

Rationally designed hyaluronic acid-based nano-complexes for pentamidine delivery.

Nanoparticles of polymeric complexes made of hyaluronic acid and polyarginine were investigated for the encapsulation of the cationic hydrophilic drug pentamidine isethionate. The interaction between the anionic hyaluronic acid and the cationic pentamidine resulting in the formation of polyelectrolyte complexes was firstly studied. Then, nanoparticles made of hyaluronic acid and polyarginine loaded with pentamidine were developed.

Uptake and intracellular distribution of different types of nanoparticles in primary human myoblasts and myotubes.

The use of nanoparticles as drug carriers in the field of skeletal muscle diseases has been poorly addressed and the interaction of nanoparticles with skeletal muscle cells has been investigated almost exclusively on C2C12 murine myoblasts. In this study we investigated the effects poly(lactide-co-glycolide) nanoparticles, mesoporous silica nanoparticles and liposomes, on the viability of primary human myoblasts and analyzed their cellular uptake and intracellular distribution in both primary human myoblasts and myotubes. Our data demonstrate that poly(lactide-co-glycolide) nanoparticles do not negatively affect myoblasts viability, contrarily to mesoporous silica nanoparticles and liposomes that induce a decrease in cell viability at the highest doses and longest incubation time.