A new application of avocado oil to enrich the biological activities of polycaprolactone membranes for tissue engineering.

The metabolites synthesized by plants to protect themselves serves as natural antimicrobial agents used in biomaterials. In this study, avocado oil (AO), was incorporated as a plant source and natural antimicrobial agent into polycaprolactone (PCL) membranes. The effects of varying AO ratios (25, 50, and 100 wt%.-PCL@25AO, PCL@50AO, PCL@100AO) on PCL membrane morphology, chemical structure, wettability, antimicrobial activity, and cell viabilities were investigated. It was demonstrated that the AO acts as a pore-forming agent in solvent-casted membranes. Young's modulus of the membranes varied between 602.68 and 31.92 MPa and more flexible membranes were obtained with increasing AO content. Inhibition zones of AO were recorded between 7.86 and 13.97 mm against clinically relevant microbial strains including bacteria, yeast, and fungi. Antimicrobial activity of AO was retained in PCL membranes at all ratios. Resazurin assay indicated that PCL@25AO membranes were cytocompatible with mouse fibroblast cells (L929 cell line) on day 6 showing 72.4% cell viability with respect to neat PCL membranes. Viability results were supported by scanning electron microscopy images and DAPI staining. The overall results of this study highlight the potential of PCL@25AO membranes as a biomaterial with antimicrobial properties, cytocompatibility, and mechanical strength suitable for various biomedical applications.

Peek dental implants coated with boron-doped nano-hydroxyapatites: Investigation of in-vitro osteogenic activity.

BACKGROUND: PEEK is a high-performance thermoplastic that has many potential uses in orthopaedics and dentistry, and it has been shown to be a substitute for titanium (Ti) implants. However, PEEK is an inherently inert material, and that characteristic limits its cellular adhesion and bone integration. The aim of this study is to determine a suitable surface modification method for increasing the osteogenic potential of polyetheretherketone (PEEK) implants used in periodontal applications. METHODS: In this work, a nanostructured porous surface is created on PEEK material by sulfonation, in sulfuric acid at room temperature for 20 min, and thus SPEEK samples were obtained. Then, PEEK and SPEEK samples were coated with boron (B) doped hydroxyapatite (HAp) nanoparticles (B-nHAp) precipitated from concentrated synthetic body fluid (10xSBF) by a microwave-assisted method conducted at 600 W. In vitro cell culture studies were carried out with periodontal ligament cells (PDL) on the samples. Osteogenic differentiation of PDL cells on PEEK, SPEEK and SPEEK-B-nHAp was evaluated using ALP activity assay, hydroxyproline assay, and RT-qPCR. RESULTS: In vitro cell culture studies disclosed improved adhesion and proliferation of PDL cells on the SPEEK and B-nHAp coated SPEEK surfaces (SPEEK-B-nHAp). Results of these assays confirmed that treated PEEK surfaces, especially SPEEK-B-nHAp, significantly enhanced osteogenic differentiation of PDL cells in vitro compared with untreated PEEK surfaces. CONCLUSION: Here a simple, easy to-use, and efficient modification method based on the properties of boron is proposed for increasing osteogenic potential of PEEK implants.

Forecasting Gastric Cancer Diagnosis, Prognosis, and Drug Repurposing with Novel Gene Expression Signatures.

Gastric cancer (GC) is a prevalent disease worldwide with high mortality and poor treatment success. Early diagnosis of GC and forecasting of its prognosis with the use of biomarkers are directly relevant to achieve both personalized/precision medicine and innovation in cancer therapeutics. Gene expression signatures offer one of the promising avenues of research in this regard, as well as guiding drug repurposing analyses in cancers. Using publicly accessible gene expression datasets from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA), we report here original findings on co-expressed gene modules that are differentially expressed between 133 GC samples and 46 normal tissues, and thus hold potential for novel diagnostic candidates for GC. Furthermore, we found two co-expressed gene modules were significantly associated with poor survival outcomes revealed by survival analysis of the RNA-Seq TCGA datasets. We identified STAT6 (signal transducer and activator of transcription 6) as a key regulator of the identified gene modules. Finally, potential therapeutic drugs that may target and reverse the expression of the identified altered gene modules examined for drug repurposing analyses and the unraveled compounds were further investigated in the literature by the text mining method. Accordingly, we found several repurposed drug candidates, including Trichostatin A, Vorinostat, Parthenolide, Panobinostat, Brefeldin A, Belinostat, and Danusertib. Through text mining analysis and literature search validation, Belinostat and Danusertib were suggested as possible novel drug candidates for GC treatment. These findings collectively inform multiple aspects of GC medical management, including its precision diagnosis, forecasting of possible outcomes, and drug repurposing for innovation in GC medicines in the future.

Dopaminergic induction of human dental pulp stem cells by photobiomodulation: comparison of 660nm laser light and polychromatic light in the nir.

Human dental pulp stem cells (hDPSCs) are able to differentiate into dopaminergic neurons and help the maintenance of partially degenerated neurons, which makes them as an alternative cell source for treatment of Parkinsons' disease (PD) patients. Here, the effect of photobiomodulation with polychromatic light source in the near infrared (NIR) range (600-1200 nm) or low level 660 nm diode laser light on hDPSCs during dopaminergic induction was investigated. Real time RT-qPCR analysis indicated that expressions of brain derived neurotrophic factor (BDNF), glial cell line derived neurotropic factor (GNDF), matrix associated protein 2 (MAP2), nuclear receptor related 1 protein (NURR1) and dopamine transporter (DAT) were increased, especially in the first 7 days of dopaminergic induction when 660 nm laser light was applied with a total energy density of 1.6 J/cm2. The activity of polychromatic light on hDPSCs depended on the differentiation media and protein type. BDNF, GDNF, NURR-1 and MAP2 expressions were increased in the presence of pre-induction factors, and decreased when the post-induction factors were added into the culture medium. In contrast with all these promising results, the dopaminergically induced hDPSCs did not show any functional characteristics of dopaminergic neurons and died after they were transferred to a new laminin coated culture plates. In conclusion, the expression of dopaminergic neuron protective protein mRNAs in hDPSCs was increased by photobiomodulation in defined conditions. However, the cells were not able to differentiate into functional dopaminergic neurons either in control or in photobiomodulated groups that are prone to cell death and exhibit immature dopaminergic neuron characteristics.

NaOH-etched/boron-doped nanohydroxyapatite-coated PEEK implants enhance the proliferation and differentiation of osteogenic cells.

The aim of the present study is to eliminate the bioinertness of polyetheretherketone (PEEK) material and to increase its osteogenic activity by applying a number of surface modifications in order to discover the most effective method. First, the surface of the bare PEEK (B-PEEK) was mechanically modified by sandblasting (S-PEEK). As a second method, physical modification was provided by etching of B-PEEK in 10 M sodium hydroxide (NaOH) solution at 60 °C for 48 h (N-PEEK). Following the sandblasting, S-PEEK samples were also etched with NaOH to obtain SN-PEEK samples. In order to increase osteogenic activity of the mechanically and/or physically modified PEEK samples, they were coated with boron-doped nanohydroxyapatite (B-nHAp) in the presence of microwave energy. Thus, B-PEEK/B-nHAp, S-PEEK/B-nHAp, N-PEEK/B-nHAp and SN-PEEK/B-nHAp samples were obtained. While water contact angles and surface roughness of the B-PEEK samples increased after modification, hydrophilicity increased with B-nHAp coating. Cell culture results demonstrated that high proliferation and differentiation capacities of MC3T3-E1 cells were obtained on the B-nHAP-coated surfaces compared to uncoated specimens. However, channeled texture of both the N-PEEK and N-PEEK/B-nHAp samples enhanced Col1a1 mRNA expression and collagen secretion in addition to increased alkaline phosphatase (ALP) activity when compared to other groups. As a result, it was determined that the bioactivity increased on the modified PEEK surfaces, but the most effective osteogenic activity was provided with B-nHAp coatings. The synergetic effect of NaOH etching and B-nHAp coatings might be used as a promising surface modification method to use PEEK material in orthopedic and dental applications with increased osteogenic activity.

Impact of selective fibronectin nanoconfinement on human dental pulp stem cells.

In this study, it was aimed to investigate the combinatory effect of biophysical and biochemical factors on human dental pulp stem cells' (hDPSCs) behavior. For this purpose, well-defined nanotopography of nanowells with two different pitch size of 109 nm and 341 nm were prepared on polyhydroxymethylsiloxane (PHMS) by using colloidal particles nanofabrication. The nanopatterned PHMS surfaces (PHMS/109 and PHMS/341) were subsequently used for fibronectin (Fn) adsorption. With this approach, nanotopographical details were combined with biochemical signals from Fn. Depending upon the size of cavities created by the nanowells, Fn molecules followed a site-selective adsorption. While they adsorbed both inside and outside the nanowells of PHMS/341, they preferred to adsorb outside the cavities of PHMS/109 surfaces. Human dental pulp stem cells were cultured on nanopatterned PHMS with or without Fn adsorption in the presence and absence of serum. Scanning electron microscopy and fluorescence microscopy analyses showed the interaction of cells was dependent on nanotopography size especially in serum-free medium. Furthermore, hDPSCs' morphology and cytoskeletal organization changed in correlation with preferential Fn adsorption. On Fn adsorbed PHMS/109 surfaces, cells displayed stretched bundles whereas, they showed extensive spreading and followed the Fn adsorbed sites inside the cavities of PHMS/341 surfaces. The observed effects are interpreted in terms of the preferential exposure of different Fn epitopes occurring on PHMS/109 and PHMS/341 as a consequence of the different hydrophilic/hydrophobic adsorbing surface.