This paper presents pioneering results on the evaluation of noble metal film hetero-structures to improve some functional characteristics of carbon-based implant materials: carbon-composite material (CCM) and carbon-fiber-reinforced polyetheretherketone (CFR-PEEK). Metal-organic chemical vapor deposition (MOCVD) was successfully applied to the deposition of Ir, Pt, and PtIr films on these carriers. A noble metal layer as thin as 1 µm provided clear X-ray imaging of 1–2.5 mm thick CFR-PEEK samples. The coated and pristine CCM and CFR-PEEK samples were further surface-modified with Au and Ag nanoparticles (NPs) through MOCVD and physical vapor deposition (PVD) processes, respectively. The composition and microstructural features, the NPs sizes, and surface concentrations were determined. In vitro biological studies included tests for cytotoxicity and antibacterial properties. A series of samples were selected for subcutaneous implantation in rats (up to 3 months) and histological studies. The bimetallic PtIr-based heterostructures showed no cytotoxicity in vitro, but were less biocompatible due to a dense two-layered fibrous capsule. AuNP heterostructures on CFR-PEEK promoted cell proliferation in vitro and exhibited a strong inhibition of bacterial growth (p < 0.05) and high in vitro biocompatibility, especially Au/Ir structures. AgNP heterostructures showed a more pronounced antibacterial effect, while their in vivo biocompatibility was better than that of the pristine CFR-PEEK, but worse than that of AuNP heterostructures. Full article

Primary hepatocytes are a major tool in biomedical research. However, obtaining high yields of variable hepatocytes is technically challenging. Most protocols rely on the two-step collagenase perfusion protocol introduced by Per Ottar Seglen in 1976. In this procedure, the liver is perfused in situ with a recirculating, constant volume of calcium-free buffer, which is maintained at 37 °C and continuously oxygenated. In a second step, the liver is removed from the carcass and perfused with a collagenase solution in order to dissociate the extracellular matrix of the liver and liberate individual cells. Finally, the dissected hepatocytes are further purified and concentrated by density-based centrifugation. However, failure in proper cannulation, incomplete enzymatic digestion or over-digestion can result in low cell yield and viability. Here we present a novel semi-automated perfusion device, which allows gentle, rapid and efficient generation of a single-cell suspension from rodent livers. In combination with prefabricated buffers, the system allows reliable and highly reproducible isolation of primary hepatocytes. Full article

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta, which leads to the motor control deficits. Recently, cell transplantation is a cutting-edge technique for the therapy of PD. Nevertheless, one key bottleneck to realizing such potential is allogenic immune reaction of tissue grafts by recipients. Cerebral dopamine neurotrophic factor (CDNF) was shown to possess immune-modulatory properties that benefit neurodegenerative diseases. We hypothesized that co-administration of CDNF with fetal ventral mesencephalic (VM) tissue can improve the success of VM replacement therapies by attenuating immune responses. Hemiparkinsonian rats were generated by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of Sprague Dawley (SD) rats. The rats were then intrastriatally transplanted with VM tissue from rats, with/without CDNF administration. Recovery of dopaminergic function and survival of the grafts were evaluated using the apomorphine-induced rotation test and small-animal positron emission tomography (PET) coupled with [¹⁸F] DOPA or [¹⁸F] FE-PE2I, respectively. In addition, transplantation-related inflammatory response was determined by uptake of [¹⁸F] FEPPA in the grafted side of striatum. Immunohistochemistry (IHC) examination was used to determine the survival of the grated dopaminergic neurons in the striatum and to investigate immune-modulatory effects of CDNF. The modulation of inflammatory responses caused by CDNF might involve enhancing M2 subset polarization and increasing fractal dimensions of 6-OHDA-treated BV2 microglial cell line. Analysis of CDNF-induced changes to gene expressions of 6-OHDA-stimulated BV2 cells implies that these alternations of the biomarkers and microglial morphology are implicated in the upregulation of protein kinase B signaling as well as regulation of catalytic, transferase, and protein serine/threonine kinase activity. The effects of CDNF on 6-OHDA-induced alternation of the canonical pathway in BV2 microglial cells is highly associated with PI3K-mediated phagosome formation. Our results are the first to show that CDNF administration enhances the survival of the grafted dopaminergic neurons and improves functional recovery in PD animal model. Modulation of the polarization, morphological characteristics, and transcriptional profiles of 6-OHDA-stimualted microglia by CDNF may possess these properties in transplantation-based regenerative therapies. Full article

Indwelling urinary catheters are employed widely to relieve urinary retention in patients. A common side effect of the use of these catheters is the formation of urinary tract infections (UTIs), which can lead not only to severe medical complications, but even to death. A number of approaches have been used to attempt reduction in the rate of UTI development in catheterized patients, which include the application of antibiotics and modification of the device surface by coatings. Many of these coatings have not seen use on catheters in medical settings due to either the high cost of their implementation, their long-term stability, or their safety. In previous work, it has been established that the simple, stable, and easily applicable sterilization surface coating 2-(3-trichlorosilylpropyloxy)-ethyl hydroxide (MEG-OH) can be applied to polyurethane plastic, where it greatly reduces microbial fouling from a variety of species for a 1-day time period. In the present work, we establish that this coating is able to remain stable and provide a similarly large reduction in fouling against Escherichia coli and Staphylococcus aureus for time periods in an excess of 30 days. This non-specific coating functioned against both Gram-positive and Gram-negative bacteria, providing a log 1.1 to log 1.9 reduction, depending on the species and day. This stability and continued efficacy greatly suggest that MEG-OH may be capable of providing a solution to the UTI issue which occurs with urinary catheters. Full article

The purpose of this in vitro study was to investigate whether different types of experimental and commercial restorative dental materials can protect dentin against acid-induced softening. Experimental composites were prepared with a photocurable mixture of methacrylates and two types of bioactive glass (45S5 and a customized low-Na F-containing formulation). Human dentin samples were prepared from mid-coronal tooth slices and immersed in lactic acid solution (pH = 4.0) at 5 mm from set specimens of restorative material. After 4, 8, 12, 16, 20, 24, 28, and 32 days, surface microhardness of dentin samples and pH of the immersion solution were measured, followed by replenishing of the immersion medium. Microstructural analysis was performed using scanning electron microscopy. The protective effect of restorative materials was determined as dentin microhardness remaining statistically similar to initial values for a certain number of acid additions. Scanning electron microscopy showed a gradual widening of dentinal tubules and proved less discriminatory than microhardness measurements. To produce a protective effect on dentin, 20 wt% of low-Na F-containing bioactive glass was needed, whereas 10 wt% of bioactive glass 45S5 was sufficient to protect dentin against acid-induced demineralization. The anti-demineralizing protective effect of experimental and commercial restoratives on dentin was of shorter duration than measured for enamel in a previous study using the same experimental approach. Full article

The development of bioactive coatings for orthopedic implants has been of great interest in recent years in order to achieve both early- and long-term osseointegration. Numerous bioactive materials have been investigated for this purpose, along with loading coatings with therapeutic agents (active compounds) that are released into the surrounding media in a controlled manner after surgery. This review initially focuses on the importance and usefulness of characterization techniques for bioactive coatings, allowing the detailed evaluation of coating properties and further improvements. Various advanced analytical techniques that have been used to characterize the structure, interactions, and morphology of the designed bioactive coatings are comprehensively described by means of time-of-flight secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), 3D tomography, quartz crystal microbalance (QCM), coating adhesion, and contact angle (CA) measurements. Secondly, the design of controlled-release systems, the determination of drug release kinetics, and recent advances in drug release from bioactive coatings are addressed as the evaluation thereof is crucial for improving the synthesis parameters in designing optimal bioactive coatings. Full article