Biocompatibility and antibacterial properties of medical stainless steel and titanium modified by alumina and hafnia films prepared by atomic layer deposition.

New methods for producing surfaces with suitable biocompatible properties are desirable due to increasing demands for biomedical devices. Stainless steel 316 L and cp- titanium specimens were coated with thin films of alumina and hafnia deposited using the atomic layer deposition method at two temperatures, 180 and 260 °C. The morphology of the films was analysed using scanning electron microscopy, and their surface energies were determined based on drop contact angle measurements.

Brain-derived neurotrophic factor modulation in response to oxidative stress and corticosterone: role of scopolamine and mirtazapine.

Unlabelled: Major Depressive Disorder (MDD) is a very complex disease, challenging to study and manage. The complexities of MDD require extensive research of its mechanisms to develop more effective therapeutic approaches. Crucial in the context of this disease is the role of brain-derived neurotrophic factor (BDNF) signaling pathway.

Functionalized retinoic acid lipid nanocapsules promotes a two-front attack on inflammation and lack of demyelination on neurodegenerative disorders.

Demyelinating disorders, with a particular focus on multiple sclerosis (MS), have a multitude of detrimental cognitive and physical effects on the patients. Current treatment options that involve substances promoting remyelination fail in the clinics due to difficulties in reaching the central nervous system (CNS). Here, the dual encapsulation of retinoic acid (RA) into lipid nanocapsules with a nominal size of 70 nm, and a low PdI of 0.

Eumelanin decorated poly(lactic acid) electrospun substrates as a new strategy for spinal cord injury treatment.

Spinal cord injury (SCI) is characterized by neuroinflammatory processes that are marked by an uncontrolled activation of microglia, which directly damages neurons. Natural and synthetic melanins represent an effective tool to treat neuroinflammation because they possess immunomodulatory properties. Here, the main objective was to evaluate the effect of eumelanin-coated poly(lactic acid) (EU@PLA) aligned microfibers on in vitro model of neuroinflammation related to spinal cord injury in terms of inflammatory mediators' modulation.

Unravelling the interactions of biodegradable dendritic nucleic acid carriers and neural cells.

Nanomedicines based on nanoparticles as carriers of therapeutics are expected to drastically influence the future of healthcare. However, clinical translation of these technologies can be very challenging. The development process of nanoparticles for biological applications encompasses the analysis and understanding of several steps , before , and subsequent clinical applications, namely, the in-depth study of biosafety, cellular interaction, and intracellular trafficking.

Mechanotransduction: Exploring New Therapeutic Avenues in Central Nervous System Pathology.

Cells are continuously exposed to physical forces and the central nervous system (CNS) is no exception. Cells dynamically adapt their behavior and remodel the surrounding environment in response to forces. The importance of mechanotransduction in the CNS is illustrated by exploring its role in CNS pathology development and progression.

Versatile fully biodegradable dendritic nanotherapeutics.

The repeated administration of non-degradable dendrimers can lead to toxicity due to their bioaccumulation. Furthermore, in drug delivery applications, carrier stability can result in low biological performance due to insufficient intracellular cargo release. A novel family of versatile, biosafe, water-soluble, and fully biodegradable PEG-dendritic nanosystems is proposed, which overcomes the limitations of the most used dendrimers.

Biocompatibility of Platinum Nanoparticles in Brain Models in Physiological and Pathological Conditions.

Platinum nanoparticles (PtNPs) have unique physico-chemical properties that led to their use in many branches of medicine. Recently, PtNPs gathered growing interest as delivery vectors for drugs, biosensors and as surface coating on chronically implanted biomedical devices for improving electrochemical properties. However, there are contradictory statements about their biocompatibility and impact on target organs such as the brain tissue, where these NPs are finding many applications.

Characterization of the Striatal Extracellular Matrix in a Mouse Model of Parkinson's Disease.

Parkinson's disease's etiology is unknown, although evidence suggests the involvement of oxidative modifications of intracellular components in disease pathobiology. Despite the known involvement of the extracellular matrix in physiology and disease, the influence of oxidative stress on the matrix has been neglected. The chemical modifications that might accumulate in matrix components due to their long half-live and the low amount of extracellular antioxidants could also contribute to the disease and explain ineffective cellular therapies.

Lipid nanocapsules to enhance drug bioavailability to the central nervous system.

The central nervous system (CNS), namely the brain, still remains as the hardest area of the human body to achieve adequate concentration levels of most drugs, mainly due to the limiting behavior of its physical and biological defenses. Lipid nanocapsules emerge as a versatile platform to tackle those barriers, and efficiently delivery different drug payloads due to their numerous advantages. They can be produced in a fast, solvent-free and scalable-up process, and their properties can be fine-tuned for to make an optimal brain drug delivery vehicle.

Exploring Poly(Ethylene Glycol)-Poly(Trimethylene Carbonate) Nanoparticles as Carriers of Hydrophobic Drugs to Modulate Osteoblastic Activity.

Current treatment options for bone-related disorders rely on a systemic administration of therapeutic agents that possess low solubility and intracellular bioavailability, as well as a high pharmacokinetic variability, which in turn lead to major off-target side effects. Hence, there is an unmet need of developing drug delivery systems that can improve the clinical efficacy of such therapeutic agents. Nanoparticle delivery systems might serve as promising carriers of hydrophobic molecules.

Tissue Response to Neural Implants: The Use of Model Systems Toward New Design Solutions of Implantable Microelectrodes.

The development of implantable neuroelectrodes is advancing rapidly as these tools are becoming increasingly ubiquitous in clinical practice, especially for the treatment of traumatic and neurodegenerative disorders. Electrodes have been exploited in a wide number of neural interface devices, such as deep brain stimulation, which is one of the most successful therapies with proven efficacy in the treatment of diseases like Parkinson or epilepsy. However, one of the main caveats related to the clinical application of electrodes is the nervous tissue response at the injury site, characterized by a cascade of inflammatory events, which culminate in chronic inflammation, and, in turn, result in the failure of the implant over extended periods of time.

An affinity-based approach to engineer laminin-presenting cell instructive microenvironments.

Laminin immobilization into diverse biological and synthetic matrices has been explored to replicate the microenvironment of stem cell niches and gain insight into the role of extracellular matrix (ECM) on stem cell behavior. However, the site-specific immobilization of this heterotrimeric glycoprotein and, consequently, control over its orientation and bioactivity has been a challenge that has limited many of the explored strategies to date. In this work, we established an affinity-based approach that takes advantage of the native high affinity interaction between laminin and the human N-terminal agrin (hNtA) domain.

Synthetic matrix enhances transplanted satellite cell engraftment in dystrophic and aged skeletal muscle with comorbid trauma.

Muscle satellite cells (MuSCs) play a central role in muscle regeneration, but their quantity and function decline with comorbidity of trauma, aging, and muscle diseases. Although transplantation of MuSCs in traumatically injured muscle in the comorbid context of aging or pathology is a strategy to boost muscle regeneration, an effective cell delivery strategy in these contexts has not been developed. We engineered a synthetic hydrogel-based matrix with optimal mechanical, cell-adhesive, and protease-degradable properties that promotes MuSC survival, proliferation, and differentiation.

Fine tuning neuronal targeting of nanoparticles by adjusting the ligand grafting density and combining PEG spacers of different length.

Unlabelled: Poly(ethylene glycol) (PEG) has been extensively used to coat the surface of nanocarriers to improve their physicochemical properties and allow the grafting of targeting moieties. Still, to date there is no common agreement on the ideal PEG coverage-density or length to be used for optimum vector performance. In this study, we aimed to investigate the impact of both PEG density and length on the vectoring capacity of neuron-targeted gene-carrying trimethyl chitosan nanoparticles.

Ibuprofen-loaded fibrous patches-taming inhibition at the spinal cord injury site.

It is now widely accepted that a therapeutic strategy for spinal cord injury (SCI) demands a multi-target approach. Here we propose the use of an easily implantable bilayer polymeric patch based on poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) that combines physical guidance cues provided by electrospun aligned fibres and the delivery of ibuprofen, as a mean to reduce the inhibitory environment at the lesion site by taming RhoA activation. Bilayer patches comprised a solvent cast film onto which electrospun aligned fibres have been deposited.

Biodegradable PEG-dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA.

One important drawback of most of the currently used dendrimers for biomedical applications is their high stability under physiological conditions that can result in cytotoxicity or complications induced by the accumulation of non-degradable synthetic materials in the organism. Particularly in the gene therapy field, vector stability can further hinder the intracellular release of the nucleic acid from the dendriplex, consequently leading to low transfection efficiencies. Therefore, biodegradable cationic dendritic structures have been eagerly awaited.

Delivering siRNA with Dendrimers: In Vivo Applications.

Over the last decades, gene therapy has emerged as a pioneering therapeutic approach to treat or prevent several diseases. Among the explored strategies, the short-term silencing of protein coding genes mediated by siRNAs has a good therapeutic potential in a clinical setting. However, the widespread use of siRNA will require the development of clinically suitable, safe and effective vehicles with the ability to complex and deliver siRNA into target cells with minimal toxicity.

Antisense Oligonucleotides Modulating Activation of a Nonsense-Mediated RNA Decay Switch Exon in the ATM Gene.

ATM (ataxia-telangiectasia, mutated) is an important cancer susceptibility gene that encodes a key apical kinase in the DNA damage response pathway. ATM mutations in the germ line result in ataxia-telangiectasia (A-T), a rare genetic syndrome associated with hypersensitivity to double-strand DNA breaks and predisposition to lymphoid malignancies. ATM expression is limited by a tightly regulated nonsense-mediated RNA decay (NMD) switch exon (termed NSE) located in intron 28.

In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles.

A major challenge in neuronal gene therapy is to achieve safe, efficient, and minimally invasive transgene delivery to neurons. In this study, we report the use of a nonviral neurotropic poly(ethylene imine)-based nanoparticle that is capable of mediating neuron-specific transfection upon a subcutaneous injection. Nanoparticles were targeted to peripheral neurons by using the nontoxic carboxylic fragment of tetanus toxin (HC), which, besides being neurotropic, is capable of being retrogradely transported from neuron terminals to the cell bodies.

High-throughput platforms for the screening of new therapeutic targets for neurodegenerative diseases.

Despite the recent progress in the understanding of neurodegenerative disorders, a lack of solid fundamental knowledge on the etiology of many of the major neurodegenerative diseases has made it difficult to obtain effective therapies to treat these conditions. Scientists have been looking to carry out more-human-relevant studies, with strong statistical power, to overcome the limitations of preclinical animal models that have contributed to the failure of numerous therapeutics in clinical trials. Here, we identify currently existing platforms to mimic central nervous system tissues, healthy and diseased, mainly focusing on cell-based platforms and discussing their strengths and limitations in the context of the high-throughput screening of new therapeutic targets and drugs.

Functionalized chitosan derivatives as nonviral vectors: physicochemical properties of acylated N,N,N-trimethyl chitosan/oligonucleotide nanopolyplexes.

Cationic polymers have recently attracted attention due to their proven potential for nonviral gene delivery. In this study, we report novel biocompatible nanocomplexes produced using chemically functionalized N,N,N-trimethyl chitosan (TMC) with different N-acyl chain lengths (C5-C18) associated with single-stranded oligonucleotides. The TMC derivatives were synthesized by covalent coupling reactions of quaternized chitosan with n-pentanoic (C5), n-decanoic (C10), and n-octadecanoic (C18) fatty acids, which were extensively characterized by Fourier transform-infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance ((1)H NMR).

Biomimetic synthetic self-assembled hydrogels for cell transplantation.

The development of three-dimensional matrices capable of recapitulating the main features of native extracellular matrix and contribute for the establishment of a favorable microenvironment for cell behavior and fate is expected to circumvent some of the main limitations of cell-based therapies. In this context, self-assembly has emerged as a promising strategy to engineer cell-compatible hydrogels. A wide number of synthetically-derived biopolymers, such as proteins, peptides and DNA/RNA, with intrinsic ability to self-assemble into well-defined nanofibrous structures, are being explored.

The Present and the Future of Degradable Dendrimers and Derivatives in Theranostics.

Interest in dendrimer-based nanomedicines has been growing recently, as it is possible to precisely manipulate the molecular weight, chemical composition, and surface functionality of dendrimers, tuning their properties according to the desired biomedical application. However, one important concern about dendrimer-based therapeutics remains-the nondegradability under physiological conditions of the most commonly used dendrimers. Therefore, biodegradable dendrimers represent an attractive class of nanomaterials, since they present advantages over conventional nondegradable dendrimers regarding the release of the loaded molecules and the prevention of bioaccumulation of synthetic materials and subsequent cytotoxicity.