Presence Of Biological Fluids Research Articles

Distinguishing Protein Corona from Nanoparticle Aggregate Formation in Complex Biological Media Using X-ray Photon Correlation Spectroscopy.

In biological systems, nanoparticles interact with biomolecules, which may undergo protein corona formation that can result in noncontrolled aggregation. Therefore, comprehending the behavior and evolution of nanoparticles in the presence of biological fluids is paramount in nanomedicine. However, traditional lab-based colloid methods characterize diluted suspensions in low-complexity media, which hinders in-depth studies in complex biological environments. Here, we apply X-ray photon correlation spectroscopy (XPCS) to investigate silica nanoparticles (SiO2) in various environments, ranging from low to high complex biological media. Interestingly, SiO2 revealed Brownian motion behavior, irrespective of the complexity of the chosen media. Moreover, the SiO2 surface and media composition were tailored to underline the differences between a corona-free system from protein corona and aggregates formation. Our results highlighted XPCS potential for real-time nanoparticle analysis in biological media, surpassing the limitations of conventional techniques and offering deeper insights into colloidal behavior in complex environments.

Mechanical properties and biocompatibility of multilayer systems based on amorphous SiN:H/SiCN:H layers on Ti6Al7Nb titanium alloy

Surfaces of metallic implants that replace diseased joints are bound to degrade over time under constant mechanical wear and corrosion, caused by the presence of biological fluids. Production of wear particles and toxic metal ions that follows can undermine both implant stability and patient’s health. To counteract this process multiple surface modifications have been proposed in scientific literature, ranging from simple nitriding to protective layers (e.g.: DLC, CN:H) and multilayer systems. This work presents a combined approach to outlined issue, using multi-staged plasma deposition with SiCN:H layer as a key component, realized using the MW CVD (Microwave Chemical Vapour Deposition) system. The study covers chemical characterization by EDS and FTIR analysis and measurements of relevant functional parameters, such as hardness, Young’s modulus, coefficient of friction, specific wear rate and wettability. Additionally, biocompatibility of modified surfaces are tested on MG-63 cells using Alamar Blue assay, flow cytometry and alkaline phosphatase (ALP) assay. Chemical and microscopic studies revealed amorphous cauliflower-like microstructures that have proven to be hydrogenated SiCN/SiN structures. The obtained layers are turned out to be biocompatible (>70 % of cell survival rate), additionally layers based on amorphous SiCN:H boost ALP activity due to combination of their chemistry and mechanical properties.

Synthesis and Evaluation of Boronated 4‐Arm Polyethylene Glycol for Application in Transmucosal Drug Delivery

AbstractPolyethylene glycol (PEG) exhibits poor residence on mucosal membranes in the presence of biological fluid, and the influence of PEG boronation on its properties has never been investigated. This project aimed to synthesise boronated 4‐arm PEG and evaluate their pH stability, thermal properties and mucoadhesiveness for potential transmucosal applications. Two types of boronated 4‐armed PEG (B4PEG1 & B4PEG2) and a boronated linear PEG (BLPEG) were synthesized. The degree of boronation, mucoadhesiveness, thermal and pH stability of the polymers were assessed using 1H NMR spectroscopy, viscometry, thermogravimetric analysis and UV–visible spectroscopy, respectively. Gel Permeation Chromatography was employed to confirm PEG boronation. The respective degrees of boronation for B4PEG1 and B4PEG2 were 32.8 % and 46.2 %. The molecular architecture and degree of PEG boronation had a remarkable influence on mucoadhesiveness, pH, and thermal stability. B4PEG2, with a branched architecture and the greatest degree of boronation, exhibited superior mucoadhesiveness and colloidal stability at pH 4 to 8, relative to B4PEG1 and BLPEG. Boronation improved the thermal stability of 4‐arm PEG. This study is the first to demonstrate that PEG boronation could enhance the pH‐sensitivity, thermal stability and mucoadhesiveness of 4‐arm PEG. Boronated 4‐arm PEGs could serve as mucoadhesive polymeric excipients for transmucosal drug delivery.

Improved Methodology for Evaluating Nanomedicine Antibacterial Properties in Biological Fluids.

Accurate assessment of nanomedicines' antibacterial properties is pivotal for their effective use in both in vitro and in vivo settings. Conventional antibacterial activity assessment methods, involving bacterial coculture with compounds on agar plates, may not fully suit nanomedicines due to their susceptibility to alterations in physicochemical properties induced by biological fluids. Furthermore, these biological fluids might even enhance the bacterial growth. This study introduces a novel, rigorous, and reproducible methodology for evaluating nanomedicine antibacterial properties using cell culture media (i.e., DMEM-FBS10%). To assess the antibacterial activity of the nanoparticles in cell culture media, superparamagnetic iron oxide nanoparticles (SPIONs) were chosen as the model nanomedicine due to their clinical significance. A comparative analysis between the traditional and our proposed methods yielded contrasting outcomes, shedding light on the significant impact of biological fluids on nanoparticle antibacterial activities. While the conventional approach suggested the antibacterial effectiveness of SPIONs against Staphylococcus aureus, our innovative method unveiled a substantial increase in bacterial growth in the presence of biological fluids. More specifically, we found a significant increase in bacterial growth when exposed to bare SPIONs at various concentrations, while the formation of a protein corona on SPION surfaces could markedly reduce the observed bacterial growth compared to the control group. These findings underscore the necessity for more refined evaluation techniques that can better replicate the in vivo environment when studying the nanomedicine's antibacterial capabilities.

Microbial Exopolysaccharide Composites in Biomedicine and Healthcare: Trends and Advances

Microbial exopolysaccharides (EPSs), e.g., xanthan, dextran, gellan, curdlan, etc., have significant applications in several industries (pharma, food, textiles, petroleum, etc.) due to their biocompatibility, nontoxicity, and functional characteristics. However, biodegradability, poor cell adhesion, mineralization, and lower enzyme activity are some other factors that might hinder commercial applications in healthcare practices. Some EPSs lack biological activities that make them prone to degradation in ex vivo, as well as in vivo environments. The blending of EPSs with other natural and synthetic polymers can improve the structural, functional, and physiological characteristics, and make the composites suitable for a diverse range of applications. In comparison to EPS, composites have more mechanical strength, porosity, and stress-bearing capacity, along with a higher cell adhesion rate, and mineralization that is required for tissue engineering. Composites have a better possibility for biomedical and healthcare applications and are used for 2D and 3D scaffold fabrication, drug carrying and delivery, wound healing, tissue regeneration, and engineering. However, the commercialization of these products still needs in-depth research, considering commercial aspects such as stability within ex vivo and in vivo environments, the presence of biological fluids and enzymes, degradation profile, and interaction within living systems. The opportunities and potential applications are diverse, but more elaborative research is needed to address the challenges. In the current article, efforts have been made to summarize the recent advancements in applications of exopolysaccharide composites with natural and synthetic components, with special consideration of pharma and healthcare applications.

A Review of Extraction and Detection of Ricin from Castor Plant and the Effect of Ricin on Humans

Ricin is a ribosome inactivating protein produced within the seeds of the castor oil plant (Ricinus communis). Ricin can be extracted from the mash of crushed castor seeds using different procedures. Ricin has 2 chains, the A chain and the B chain. It is extremely potent to mammals, being able to kill 1500 cells per minute in small doses. Castor bean plants are grown as an ornamental plant and are found in most households in parks around India, eastern Africa, and the south-eastern Mediterranean Basin. Methods of detection for ricin have been found, but not one that takes into account its presence in biological fluids. Ricin has also been found to be an immunotoxin against cancer, and it could be used as a medication in the future.

Circulating microRNAs as novel non-invasive biomarkers of paediatric celiac disease and adherence to gluten-free diet.

SummaryBackgroundCeliac Disease (CD) is a multifactorial autoimmune enteropathy (with a prevalence of approximately 1% worldwide) that exhibits a wide spectrum of clinical, serological and histological manifestations. For the diagnosis of paediatric CD, the gold standard is the combination of serological tests (with high TGA-IgA values greater than 10 times the upper limit of normal) and duodenal biopsy (with a positive TGA-IgA but low titer). Therefore, a diagnostic test that totally excludes an invasive approach has not been discovered so far and the discovery of novel biological markers would represent an undoubted advantage for the diagnosis of CD and prognostic evaluation. MicroRNAs (miRNAs), small non-coding RNAs (18–22 nucleotides) that regulate gene expression at post-transcriptional level and play important roles in many biological processes, represent a novel class of potential disease biomarkers. Their presence in biological fluids (i.e., serum, plasma, saliva, urine) provides the opportunity to employ circulating miRNAs as novel non-invasive biomarkers.MethodsIn our prospective observational study, we examined the expression of circulating miRNAs in a cohort of CD patients (both at diagnosis and on gluten-free diet, respectively referred as CD and GFD) compared to healthy controls. By small RNA-Seq we discovered a set of circulating miRNAs that were further validated by qPCR with specific assays.FindingsWe found that out of the 13 miRNAs able to discriminate the three groups (i.e., CD, GFD and controls), three of them, namely miR-192-5p, miR-215-5p and miR-125b-5p (alone or in combination), were able to discriminate these three groups with high accuracy and specificity.InterpretationOur conclusions emphasize that these circulating miRNAs can be employed not only for the diagnosis of CD patients with a low TGA-IgA titer but also to monitor the adherence to a gluten-free diet by CD patients. In conclusion, we suggest the use of the circulating miRNAs identified in this work as a novel diagnostic and follow-up tool for paediatric CD.FundingThis work was supported by Fondazione Celiachia Onlus (FC) Grant n° 018/FC/2013 and by Italian Ministry of Health (Ricerca Corrente).

Odorant-binding proteins of mammals.

Odorant-binding proteins (OBPs) of vertebrates belong to the lipocalin superfamily and perform a dual function: solubilizing and ferrying volatile pheromones to the olfactory receptors, and complexing the same molecules in specialized glands and assisting their release into the environment. Within vertebrates, to date they have been reported only in mammals, apart from two studies on amphibians. Based on the small number of OBPs expressed in each species, on their sites of production outside the olfactory area and their presence in biological fluids known to be pheromone carriers, such as urine, saliva and sexual secretions, we conclude that OBPs of mammals are specifically dedicated to pheromonal communication. This assumption is further supported by the observation that some OBPs present in biological secretions are endowed with their own pheromonal activity, adding renewed interest to these proteins. Another novel piece of evidence is the recent discovery that glycosylation and phosphorylation can modulate the binding activity of these proteins, improving their affinity to pheromones and narrowing their specificity. A comparison with insects and other arthropods shows a completely different scenario. While mammalian OBPs are specifically tuned to pheromones, those of insects, which are completely different in sequence and structure, include carriers for general odorants in addition to those dedicated to pheromones. Additionally, whereas mammals adopted a single family of carrier proteins for chemical communication, insects and other arthropods are endowed with several families of semiochemical-binding proteins. Here, we review the literature on the structural and functional properties of vertebrate OBPs, summarize the most interesting new findings and suggest possible exciting future developments.

Clinical significance of STEAP1 extracellular vesicles in prostate cancer

BackgroundExtracellular vesicles (EVs) are cell-derived lipid bilayer enclosed structures shed from the plasma membrane by all cell types. Evidence of EV presence in biological fluids has led to considerable efforts focused on identifying their cargo and determining their utility as a non-invasive diagnostic platform for cancer. In this study, we identify circulating STEAP1 (six-transmembrane epithelial antigen of the prostate 1)-positive EVs in the plasma of healthy males and prostate cancer patients and evaluate its diagnostic and prognostic significance.MethodsSTEAP1 was identified on EVs in prostate cancer patient plasma. EVs were validated using electron microscopy, Western blot, nanoparticle tracking analysis, and nanoscale flow cytometry. STEAP1-positive EVs were quantified for 121 males with prostate cancer and 55 healthy age-matched control males. An evaluation of STEAP1 in prostate cancer tissue was also performed using established prostate cancer cohort data (TCGA, MSKCC, and SU2C/PCF Dream Team).ResultsEvaluation of STEAP1-positive EVs by nanoscale flow cytometry identified a significant increase in prostate cancer patient plasma compared to healthy males. However, no association was found between total STEAP1 EV levels and disease recurrence or overall survival. Cohort data from prostate cancer tissue also found STEAP1 to be elevated in prostate cancer while no significant association with recurrence or overall survival was identified.ConclusionsSTEAP1 is known to be enriched on the cells of the prostate with potential clinical significance in prostate cancer. Our results identify and quantitate STEAP1-positive EVs in plasma and provide rationale for a STEAP1 EV-based liquid biopsy as a diagnostic strategy in prostate cancer.

The Use of circRNAs as Biomarkers of Cancer.

CircRNAs are a subclass of lncRNAs that have been found to be abundantly present in a wide range of species, including humans. CircRNAs are generally produced by a noncanonical splicing event called backsplicing that is dependent on the canonical splicing machinery, giving rise to circRNAs classified into three main categories: exonic circRNA, circular intronic RNA, and exon-intron circular RNA. Notably, circRNAs possess functional importance and display their functions through different mechanisms of action including sponging miRNAs, or even being translated into functional proteins. In addition, circRNAs also have great potential as biomarkers, particularly in cancer, thanks to their high stability, tissue type and developmental stage specificity, and their presence in biological fluids, which make them promising candidates as noninvasive biomarkers. In this chapter, we describe the most commonly used techniques for the study of circRNAs as cancer biomarkers, including high-throughput techniques such as RNA-Seq and microarrays, and other methods to analyze the presence of specific circRNAs in patient samples.

A Modified Chemiluminescent Method for Determination of the Antioxidant Capacity of Biological Fluids and Tissues

Abstract—In this study we present a modified method for determination of the antioxidant capacity of biological fluids and tissues based on the use of a chemiluminescent model system in which oxidation of luminol was induced by 2,2'-azobis(2-amidinopropane) dihydrochloride. It was shown that the addition of EDTA as an extra component gives the system a number of advantages. The intensity of chemiluminescence at the stationary stage was increased substantially (by 6–7 times) and stationarity remained unchanged for a long period of time (more than 1 h). As well, it should be noted that no significant increase in the intensity of chemiluminescence occurred in the presence of biological fluids or individual antioxidants (human serum albumin and ascorbic acid) after the end of the latent period but it was observed in the absence of EDTA. Taking the fact into account that the values of the latent periods that were determined while introducing some low-molecular-weight antioxidants (trolox and uric acid) into our system, as well as human biological fluids (blood serum and tear fluid), were not significantly different from those obtained in the system without EDTA, we suppose that EDTA had no impact on luminol oxidation reactions. The proposed system can also be used to evaluate antioxidant capacity of various tissues. The obtained data are discussed in terms of prospects for the use of the proposed modified method for determination of the antioxidant capacity of biological material in clinical practice.

Effect of some organic binders on the mechanical strength of hydroxyapatite-based biocements

AbstractIn the present study, aiming to control the setting reaction and to increase the strength of hydroxyapatite-based biocements, gelatin, citric acid and malonic acid, and combinations of them, were used as binders. The mechanical strength of the developed biocements was evaluated after 1 to 15 days of exposure (aging) to air with 100% relative humidity at 37-40 °C. Especially for the case of gelatin, the mechanical properties of the biocements increased as a function of aging time in the humid environment. In this case, the standard compressive strength increased from ∼19 to ∼40 MPa, while the diametral compressive strength increased from ∼2 to ∼12 MPa, between day 1 and day 15 of aging. These values are similar to those reported in the past for HAp-containing biocements added with a variety of organic or inorganic binders. However, the resulting setting times were too long. Thus, it was proposed that crosslinking of gelatin by a suitable chemical agent during the application of the prepared HAp-based biocements could be a potential way to control their handling and setting characteristics, while preserving their good mechanical properties, good biocompatibility, and good solubilization characteristics in the presence of biological fluids.

Aptamer-displaying peptide amphiphile micelles as a cell-targeted delivery vehicle of peptide cargoes

Peptide amphiphile micelles (PAMs) are attractive vehicles for the delivery of a variety of therapeutic and prophylactic peptides. However, a key limitation of PAMs is their lack of preferential targeting ability. In this paper, we describe our design of a PAM system that incorporates a DNA oligonucleotide amphiphile (antitail amphiphile—AA) to form A/PAMs. A cell-targeting DNA aptamer with a 3′ extension sequence (tail) complementary to the AA is annealed to the surface to form aptamer-displaying PAMs (Aptamer~A/PAMs). Aptamer~A/PAMs are small, anionic, stable nanoparticles capable of delivering a large mass percentage peptide amphiphile (PA) compared to targeting DNA components. Aptamer~A/PAMs are stable for over 4 h in the presence of biological fluids. Additionally, the aptamer retains its cell-targeting properties when annealed to the A/PAM, thus leading to enhanced delivery to a specifically-targeted B-cell leukemia cell line. This exciting modular technology can be readily used with a library of different targeting aptamers and PAs, capable of improving the bioavailability and potency of the peptide cargo.

Surface Modifications of Nanoparticles for Stability in Biological Fluids.

Due to the high surface: volume ratio and the extraordinary properties arising from the nanoscale (optical, electric, magnetic, etc.), nanoparticles (NPs) are excellent candidates for multiple applications. In this context, nanoscience is opening a wide range of modern technologies in biological and biomedical fields, among others. However, one of the main drawbacks that still delays its fast evolution and effectiveness is related to the behavior of nanomaterials in the presence of biological fluids. Unfortunately, biological fluids are characterized by high ionic strengths which usually induce NP aggregation. Besides this problem, the high content in biomacromolecules—such as lipids, sugars, nucleic acids and, especially, proteins—also affects NP stability and its viability for some applications due to, for example, the formation of the protein corona around the NPs. Here, we will review the most common strategies to achieve stable NPs dispersions in high ionic strength fluids and, also, antifouling strategies to avoid the protein adsorption.

Persistence of Polydimethylsiloxane Condom Lubricants.

Polydimethylsiloxane (PDMS) is commonly used to lubricate condoms. The detection of PDMS on swabs from complainants can be used to support an allegation of sexual assault. Previous research has focused on establishing analytical techniques for detecting PDMS. This research examined the persistence of PDMS on the penis, in the vagina, in the mouth, and on skin. The longest PDMS detection times were 20h on the penis, 35h in the vagina, and 52h on skin. PDMS was detected up to 4h in the mouth if the participant did not eat or drink and up to 9h if the participant slept. PDMS was not detected in the mouth after eating or drinking. The presence of biological fluids had no detrimental effect on the analysis. Aqueous extraction of swabs for DNA did not remove any significant amount of PDMS; hence, swab remains could be subsequently analyzed for PDMS.

Estudio de selección de microRNA como posibles biomarcadores de aneurisma de aorta abdominal

IntroductionMicroRNAs (miRs) are small RNA molecules that are involved in several biological processes. Due to their stability and their presence in biological fluids, several studies over the last few years have focused on the use of miRs as biomarkers of different pathologies. ObjectiveSelection of a group of miRs candidates to be validated as potential biomarkers of abdominal aortic aneurysm (AAA). Material and methodsA total of 179 miRs were quantified in 7 patients with AAA and in 7 healthy donors, using predesigned panels based on RT-qPCR technology. ResultsA total of 10 miRs, dysregulated in patients, were selected as good candidates for studying them as biomarkers. It has been observed that most of these miRs participate in several biological processes related to the formation and development of AAAs. ConclusionAdditional, as well as validation, studies are needed, but some of these miRs could be non-invasive AAA biomarkers.

Transfer of Multidrug Resistance Among Acute Myeloid Leukemia Cells Via Extracellular Vesicles and Their Micrornas Cargo

Resistance of cancer cells to chemotherapy is a major issue in acute myeloid leukemia (AML) and is usually due to a clonal selection of resistant leukemic cells. Recently, a horizontal transfer of chemoresistance among tumor cells has been reported via extracellular vesicles (EVs). EVs are vesicles ranging from 0.03 to 1µm generated by almost all cell types. They carry cellular components such as nucleic acids, membrane and cytosolic proteins. By interacting with cells and by transferring their content, these vesicles could modify target cells’ phenotype. Because of their presence in biological fluids, a lot of studies have tried to use EVs as biomarkers.The aim of this research is to investigate the role of EVs in chemoresistance in AML. For this purpose, the sensitive strain of the promyelocytic leukemia HL60 cell line was compared to its multiresistant strain: HL60/AR. The latter overexpresses multidrug resistance-associated protein 1 (MRP1), an efflux pump conferring resistance to anthracyclines. The transfer of this resistance between the two strains is obtained by treating HL60 with EVs generated by HL60/AR.The production of EVs by HL60/AR was confirmed by transmission electron microscopy. EVs from around 100 to 800 nm were highlighted. EVs from HL60/AR were then isolated by ultracentrifugation and their interaction with HL60 was investigated by labeling EVs with a fluorescent lipid membrane linker. The transmission of this fluorescence to HL60 was monitored by flow cytometry and demonstrated a binding or an incorporation of EVs.In order to check if this interaction has an impact on HL60 resistance to daunorubicin, HL60 were treated with EVs, once for 20 hours or four consecutive times for 48 hours each. The resistance to daunorubicin of EVs-treated HL60 was then assessed by a MTT cytotoxicity assay and revealed that EVs increase survival of cells to daunorubicin. The resistant profile between the cells treated once or four times with EVs were somewhat different and highlighted a potential implication of nucleic acids cargo in this resistance transfer. Indeed, nucleic acids transferred by EVs would need more than 20 hours to impact target cells.Afterwards, we investigated the changes in phenotype that could be responsible for this increased resistance of EVs-treated cells. First, the expression of MRP1 was evaluated by a flow cytometry drug retention assay based on the fluorescence exhibited by daunorubicin and consisting in analysis by flow cytometry of the daunorubicin retention of cells with or without the presence of a specific MRP1 inhibitor. This experiment emphasized an expression of MRP1 after EVs treatment. Oxidative stress also plays an important role in daunorubicin cytotoxicity. Thus reactive oxygen species (ROS) generation assays were performed on EVs-treated cells. These cells showed a decreased production of daunorubicin-induced ROS.We finally analyzed the microRNAs content of isolated EVs. This was performed by TaqMan® Human MicroRNA Array on EVs from HL60/AR but also on EVs generated by HL60. This experiment aimed at highlighting the microRNAs cargo potentially involved in this chemoresistance transfer but also at identifying microRNAs differentially expressed between the two strains to serve as biomarker of chemoresistance in vivo. Out of the 380 microRNAs tested, 32 presented a differential expression between HL60 and HL60/AR. Among them, 5 microRNAs presented a more than 8-fold change between the two strains: miR-19b, miR-20a, miR-488, miR-519a and miR-523. miR-519a was the only microRNA more expressed in EVs produced by HL60, compared to EVs from HL60/AR.In conclusion, this study demonstrates the ability of resistant leukemic cells to transfer, at least partially, their chemoresistance via EVs. This could be due to a direct transfer of MRP1 transported by EVs but also to a nucleic acid transfer. In this context, some microRNAs have been highlighted for their high differential expression in EVs between sensitive and chemoresistant cells. These results bring out a potential clinical use of these circulating microRNAs as chemoresistance biomarkers in AML. DisclosuresNo relevant conflicts of interest to declare.

The effectiveness of the RSID confirmatory test kit for human alpha amylase: the effects of environmental factors and substrate materials

The investment in time and money that DNA analyses involves, provides a justification for forensic laboratories to carry out prior tests to ensure the presence of biological fluid in samples. The RSID kit has already been evaluated for forensic use, but its effectiveness on forensic casework samples is almost impossible to predict. Moreover, forensic reports presented before a court of law must justify the methods used to generate their findings. Consequently, trials to know how factors – such as the characteristics of the donor, the substrate and environmental conditions – can affect the kit’s efficacy are essential. This study evaluates some of these factors. For this aim, samples were made using lyophilized human salivary alpha amylase, with known concentrations, on different materials. Then were distributed in two groups, A (not protected) and B (stored and protected) to evaluate possible differences in the effectiveness of the test. The results show how those factors affect the kit’s performance, and, moreover, demonstrate that, contrary to the results that the literature provides for samples in solutions, the kit is more effective on saliva than on alpha amylase. Once again, this highlights the different behaviour of forensic casework samples compared with those that were used in the kit’s evaluation.

Titanium: a review on exposure, release, penetration, allergy, epidemiology, and clinical reactivity.

Exposure to titanium (Ti) from implants and from personal care products as nanoparticles (NPs) is common. This article reviews exposure sources, ion release, skin penetration, allergenic effects, and diagnostic possibilities. We conclude that human exposure to Ti mainly derives from dental and medical implants, personal care products, and foods. Despite being considered to be highly biocompatible relative to other metals, Ti is released in the presence of biological fluids and tissue, especially under certain circumstances, which seem to be more likely with regard to dental implants. Although most of the studies reviewed have important limitations, Ti seems not to penetrate a competent skin barrier, either as pure Ti, alloy, or as Ti oxide NPs. However, there are some indications of Ti penetration through the oral mucosa. We conclude that patch testing with the available Ti preparations for detection of type IV hypersensitivity is currently inadequate for Ti. Although several other methods for contact allergy detection have been suggested, including lymphocyte stimulation tests, none has yet been generally accepted, and the diagnosis of Ti allergy is therefore still based primarily on clinical evaluation. Reports on clinical allergy and adverse events have rarely been published. Whether this is because of unawareness of possible adverse reactions to this specific metal, difficulties in detection methods, or the metal actually being relatively safe to use, is still unresolved.

Development of an Injectable Dopamine‐conjugated Poly(organophophazene) Hydrogel for Hemostasis

Hemostatic agents are important for minimizing blood loss to improve the patient status during surgery. Most currently used hemostatic agents have limitations such as poor adhesion in the presence of biological fluids, allergic response, and inflammation. We developed a dopamine‐conjugated injectable thermosensitive hydrogel to overcome these limitations through the application of a relatively safe hydrogel for biocompatibility, thermosensitivity to induce tight interactions, and mussel‐induced adhesion. Dopamine as a mussel inspired material was conjugated to an injectable thermosensitive poly(organophosphazene) hydrogel, which showed the potential for application as a hemostatic agent because of its high biocompatibility, injectability, slow mass loss, easy preparation, and hemostatic effect.