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Keywords = platelet compatibility

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18 pages, 1436 KiB  
Article
Application of Platelet-Rich Fibrin and Concentrated Growth Factors as Carriers for Antifungal Drugs—In Vitro Study
by Wojciech Niemczyk, Małgorzata Kępa, Jacek Żurek, Ali Aboud, Dariusz Skaba and Rafał Wiench
J. Clin. Med. 2025, 14(14), 5111; https://doi.org/10.3390/jcm14145111 - 18 Jul 2025
Viewed by 231
Abstract
Background: Fungal infections, particularly those caused by Candida species, pose a serious threat to immunocompromised individuals, and therapeutic options are limited due to toxicity and resistance concerns. This in vitro study aimed to explore the feasibility of using liquid fractions of autologous [...] Read more.
Background: Fungal infections, particularly those caused by Candida species, pose a serious threat to immunocompromised individuals, and therapeutic options are limited due to toxicity and resistance concerns. This in vitro study aimed to explore the feasibility of using liquid fractions of autologous platelet concentrates (APCs), namely concentrated platelet-rich fibrin (c-PRF) and liquid-phase concentrated growth factor (LPCGF), as carriers for antifungal drugs. Methods: The research was conducted in two phases: first, to evaluate the inherent antifungal properties of different APCs; and second, to assess their effectiveness as drug carriers for fluconazole and voriconazole against Candida albicans, Candida glabrata, and Candida krusei. Results: Results showed that APCs alone exhibited no direct antifungal effects. However, when combined with antifungal agents, notable inhibition zones were observed—especially with voriconazole against C. krusei and fluconazole against C. glabrata using c-PRF. Both c-PRF and LPCGF were compatible with the drugs and did not hinder clot formation. Conclusions: These findings suggest that APCs can act as effective vehicles for localized antifungal drug delivery and warrant further investigation for clinical application in treating fungal-related oral diseases. Full article
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13 pages, 1716 KiB  
Case Report
An Unusual Case of Essential Thrombocythemia and Acute Kidney Injury: Case Report and Literature Review
by Celia Rodríguez Tudero, Alberto Martín Arribas, Patricia Antúnez Plaza, José C. De La Flor, Alexandra Lizarazo Suárez and María Pilar Fraile-Gómez
Diseases 2025, 13(5), 162; https://doi.org/10.3390/diseases13050162 - 21 May 2025
Viewed by 519
Abstract
Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by the uncontrolled proliferation of megakaryocytes and sustained thrombocytosis. Although its impact on renal function is not well established, a few case reports have described glomerular involvement and associated kidney impairment. Case Report: We [...] Read more.
Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by the uncontrolled proliferation of megakaryocytes and sustained thrombocytosis. Although its impact on renal function is not well established, a few case reports have described glomerular involvement and associated kidney impairment. Case Report: We present the case of a 79-year-old man with ET and stage 3b/A2 chronic kidney disease (CKD), who was admitted with severe acute kidney injury (AKI). This episode was associated with a progressive rise in platelet count, reaching 1,350,000/μL after discontinuation of anagrelide and loop diuretics. Renal biopsy (RB) revealed structural lesions compatible with a myeloproliferative neoplasm, including acute tubular necrosis (ATN), glomerulomegaly, and thrombotic microangiopathy (TMA). Cytoreductive therapy with hydroxyurea and corticosteroids was initiated, resulting in improvement of renal function and achievement of complete hematologic remission. Discussion: During follow-up, a linear correlation was observed between increasing platelet counts and declining renal function, underscoring the need for dynamic therapeutic adjustment and close monitoring to prevent progression to end-stage renal disease (ESRD). Conclusions: This case highlights the importance of nephrological evaluation in patients with ET and supports the role of cytoreductive therapy in managing ET-associated renal complications. Full article
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16 pages, 4105 KiB  
Article
Biosafety and Blood Compatibility of Graphene Oxide Particles in In Vitro Experiments
by Yuriy Prylutskyy, Patrycja Bełdzińska, Natalia Derewońko, Tetiana Halenova, Nataliia Raksha, Marcin Zakrzewski, Grzegorz Gołuński, Svitlana Prylutska, Uwe Ritter, Olexii Savchuk and Jacek Piosik
Materials 2025, 18(9), 2128; https://doi.org/10.3390/ma18092128 - 6 May 2025
Viewed by 502
Abstract
Graphene oxide (GO), owing to its extraordinary application prospects in biomedicine, is attracting growing research attention. However, the biosafety and blood compatibility of GO required for its clearance for use in clinical trials remain elusive. Therefore, we studied the mutagenic properties of GO [...] Read more.
Graphene oxide (GO), owing to its extraordinary application prospects in biomedicine, is attracting growing research attention. However, the biosafety and blood compatibility of GO required for its clearance for use in clinical trials remain elusive. Therefore, we studied the mutagenic properties of GO as well as its cell toxicity and blood compatibility. Prior to biological experiments, we assessed the structural organization of GO using dynamic light scattering and microscopic visualization methods. The results of both the Ames mutagenicity test performed on Salmonella enterica serovar Typhimurium TA98 and TA102 strains and the cytotoxicity test on noncancerous, immortalized human keratinocytes revealed no mutagenic or toxic effects of GO. Simultaneously, GO reduced the viability of the MelJuSo human melanoma cell line. A blood compatibility assay revealed that a concentration of 10 μg/mL was critical for GO biosafety, as greater concentrations induced diverse side effects. Specifically, GO disrupts erythrocytes’ membranes in the dose-dependent manner. Moreover, GO at higher concentrations both inhibited the process of ADP (a physiological platelet agonist)-induced cell aggregation and affected their disaggregation process in platelet-rich plasma. However, in the blood clotting assessment, GO showed no effects on the activated partial thromboplastin time, prothrombin time, or thrombin time of the platelet-poor plasma. The obtained results clearly indicate that the relationship between the GO preparation method, its size, and concentration and biosafety must be cautiously monitored in the context of further possible biomedical applications. Full article
(This article belongs to the Section Carbon Materials)
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25 pages, 7466 KiB  
Article
Analysis of the Expression and Activity of Cyclooxygenases COX-1 and COX-2 in THP-1 Monocytes and Macrophages Cultured with Xenogenic Collagen Matrices Biofunctionalized with the Injectable Platelet-Rich Fibrin
by Agnieszka Droździk, Katarzyna Barczak, Mateusz Bosiacki, Patrycja Kupnicka, Diana Cenariu, Willi Andrei Uriciuc, Dariusz Chlubek, Mariusz Lipski, Marek Droździk and Irena Baranowska-Bosiacka
Int. J. Mol. Sci. 2025, 26(9), 4386; https://doi.org/10.3390/ijms26094386 - 5 May 2025
Viewed by 1082
Abstract
Xenogenic collagen matrices are used in clinical practice for soft tissue augmentation around teeth and implants, either alone or biofunctionalized with injectable platelet-rich fibrin (iPRF). Their direct interaction with inflammatory cells may influence both healing and destructive inflammation processes. Therefore, expression of cyclooxygenases [...] Read more.
Xenogenic collagen matrices are used in clinical practice for soft tissue augmentation around teeth and implants, either alone or biofunctionalized with injectable platelet-rich fibrin (iPRF). Their direct interaction with inflammatory cells may influence both healing and destructive inflammation processes. Therefore, expression of cyclooxygenases (COX-1 and COX-2) and prostanoids (PGE2 and TXB2) was studied in THP-1 monocyte/macrophage cultures exposed to porcine collagen matrices (a non-cross-linked monolayer scaffold composed of collagen type I, collagen type III, and elastin (MLCM), a bilayer scaffold made of collagen types I and III (BLCM), and a volume-stable cross-linked monolayer scaffold (VSCM)). The study showed that VSCM and MLCM significantly reduced PGE2 concentrations in THP-1 monocyte cultures. iPRF further reduced PGE2 concentrations when exposed to MLCM. In contrast, incubation of THP-1 monocytes with VSCM and BLCM resulted in a significant increase in TXB2 concentrations compared with control conditions. Incubation of macrophages with MLCM, VSCM, and BLCM increased PGE2 concentrations, with VSCM and BLCM additionally increasing TXB2 concentrations. iPRF in macrophage cultures with VSCM and BLCM also resulted in increased PGE2 and TXB2 concentrations compared with control conditions. Confocal microscopy revealed no visible differences in COX-1 immunoexpression in monocytes and macrophages cultured with collagen matrices, either with or without iPFR. Weak positive COX-2 immunofluorescence was observed in monocytes, while moderate positive immunofluorescence was detected in macrophages. In conclusion, it can be suggested that the studied collagen matrices interact with monocytes/macrophages, with MLCM exhibiting the highest compatibility. Full article
(This article belongs to the Special Issue Targeting Collagen-Related Therapy)
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16 pages, 4962 KiB  
Article
Design and Numerical Simulation of a Standing Surface Acoustic Wave-Based Microdevice for Whole Blood Cell Separation
by Maryam Hajimoradi, Moein Talebian Gevari, Keith Robert Pullen and Mohammad Mojaddam
Computation 2025, 13(2), 42; https://doi.org/10.3390/computation13020042 - 6 Feb 2025
Viewed by 1156
Abstract
Standing surface acoustic wave (SSAW)-based acoustofluidics is widely used due to its compatibility with soft materials and polymer structures. In the presence of an acoustic field, particles move either toward pressure nodes or anti-nodes according to their contrast factor. Using this technique, blood [...] Read more.
Standing surface acoustic wave (SSAW)-based acoustofluidics is widely used due to its compatibility with soft materials and polymer structures. In the presence of an acoustic field, particles move either toward pressure nodes or anti-nodes according to their contrast factor. Using this technique, blood cells with a certain characteristic can be oriented in different streamlines in a microchannel. The cumulative effect of parameters, such as the inlet velocity ratio of the buffer solution to the blood sample, acoustic frequency, voltage, and channel geometry, is key to effective separation in these microfluidic chips. In this study, simultaneous separation of white blood cells, red blood cells, and platelets in one stage is simulated by means of numerical calculations. The linear constitutive equation for the piezoelectric substrate, the Helmholtz equation for the acoustic field, and the Navier–Stokes equations for fluid mechanics are solved simultaneously to precisely capture the blood cell behavior in the SSAW-based device. The results show that whole blood cell separation can be achieved using a velocity ratio of 6.25, a resonance frequency of 8.28 MHz, and a voltage of 8.5 V in the proposed five-outlet microfluidic chip. Full article
(This article belongs to the Section Computational Engineering)
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12 pages, 1750 KiB  
Article
Mineral Filler Hybridization in Recycled Polyethylene Terephthalate
by Marcel Droß, Max Ehleben and Klaus Dröder
Polymers 2025, 17(3), 259; https://doi.org/10.3390/polym17030259 - 21 Jan 2025
Viewed by 1039
Abstract
This study focused on evaluating the mechanical, thermal, and morphological properties of recycled polyethylene terephthalate (RPET) hybrid mineral-filled composites containing fine acicular wollastonite, mica phlogopite, and talc platelets. Depending on the filler content, both single mineral-filled composites as well as hybrid mineral–filler composites [...] Read more.
This study focused on evaluating the mechanical, thermal, and morphological properties of recycled polyethylene terephthalate (RPET) hybrid mineral-filled composites containing fine acicular wollastonite, mica phlogopite, and talc platelets. Depending on the filler content, both single mineral-filled composites as well as hybrid mineral–filler composites were investigated. The maximum nominal filler content was set to 20% by weight with varying ratios for combinations of the wollastonite–mica and wollastonite–talc composites, respectively. Aside from the tensile, compression, and flexural properties, the heat distortion temperature and degree of crystallinity were carried out. Moreover, the dynamical response of the hybrid mineral-filled composites on different frequencies (1 Hz, 2 Hz, 5 Hz, and 10 Hz) was considered. By using scanning electron microscope photography, the fracture surface and the morphology of the composite material were observed. The results demonstrated enhanced stiffness, strengths, and thermal stability for all hybrid mineral-filled composites. In particular, the wollastonite–talc-filled RPET composites revealed a good compatibility and showed the most beneficial results. Full article
(This article belongs to the Section Polymer Composites and Nanocomposites)
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22 pages, 5777 KiB  
Article
Advancing Adult-Acquired Flatfoot Deformity Treatment: Enhanced Biomechanical Support Through Graphene Oxide-Integrated Bioengineered Grafts Tested In Silico
by Sebastián Nieto, Mónica Gantiva-Díaz, María A. Hoyos, Yuliet Montoya, Juan C. Cruz and Christian Cifuentes-De la Portilla
J. Funct. Biomater. 2024, 15(11), 335; https://doi.org/10.3390/jfb15110335 - 9 Nov 2024
Cited by 1 | Viewed by 1437
Abstract
Adult-Acquired Flatfoot Deformity (AAFD) is a progressive orthopedic condition causing the collapse of the foot’s medial longitudinal arch, often linked with injuries to the plantar arch’s passive stabilizers, such as the spring ligament (SL) and plantar fascia. Conventional treatment typically involves replacing the [...] Read more.
Adult-Acquired Flatfoot Deformity (AAFD) is a progressive orthopedic condition causing the collapse of the foot’s medial longitudinal arch, often linked with injuries to the plantar arch’s passive stabilizers, such as the spring ligament (SL) and plantar fascia. Conventional treatment typically involves replacing the SL with synthetic material grafts, which, while providing mechanical support, lack the biological compatibility of native ligaments. In response to this shortcoming, our study developed an electrospun, twisted polymeric graft made of polycaprolactone (PCL) and type B gelatin (GT), enhanced with graphene oxide (GO), a two-dimensional nanomaterial, to bolster biomechanical attributes. The addition of GO aimed to match the native ligamentous tissue’s mechanical strength, with the PCL-GT-GO 2.0% blend demonstrating an optimal Young’s modulus of 240.75 MPa. Furthermore, the graft showcased excellent biocompatibility, evidenced by non-hemolytic reactions, suitable wettability and favorable platelet aggregation—essential features for promoting cell adhesion and proliferation. An MTT assay revealed cell viability exceeding 80% after 48 h of exposure, highlighting the potential of the graft as a regenerative scaffold for affected ligaments. Computational modeling of the human foot across various AAFD stages assessed the graft’s in situ performance, with the PCL-GT-OG 2.0% graft efficiently preventing plantar arch collapse and offering hindfoot pronator support. Our study, based on in silico simulations, suggests that this bioengineered graft holds significant promise as an alternative treatment in AAFD surgery, marking a leap forward in the integration of advanced materials science for enhanced patient care. Full article
(This article belongs to the Special Issue Medical Application of Functional Biomaterials (2nd Edition))
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16 pages, 2544 KiB  
Article
Monitoring Cell Activation and Extracellular Vesicle Generation in Platelet Concentrates for Transfusion
by Ana Kolenc, Maja Grundner, Irma Hostnik and Elvira Maličev
Int. J. Mol. Sci. 2024, 25(21), 11577; https://doi.org/10.3390/ijms252111577 - 28 Oct 2024
Viewed by 1239
Abstract
Platelets play a crucial role in blood transfusions, and understanding the changes that occur during their storage is important for maintaining the quality of preparations. In this study, we examined key alternating factors, with a particular focus on platelet activation and the release [...] Read more.
Platelets play a crucial role in blood transfusions, and understanding the changes that occur during their storage is important for maintaining the quality of preparations. In this study, we examined key alternating factors, with a particular focus on platelet activation and the release of extracellular vesicles. Additionally, we compared two detection methods—imaging flow cytometry (IFC) and nanoparticle tracking analysis (NTA)—for their effectiveness in detecting particles. Platelet concentrates were prepared by pooling buffy coats from five blood group-compatible donors in an additive solution. Samples were analysed after one, three, and seven days of storage for residual white blood cells (WBCs), glucose levels, platelet activation, and extracellular vesicle concentrations. Over the storage period, the total platelet concentration decreased slightly, while the residual WBC count remained stable. Glucose levels declined, whereas platelet activation and extracellular vesicle concentration increased, with a positive correlation between the two. The particle size remained relatively unchanged throughout the storage period. Ultimately, despite controlled processing and storage conditions, platelet activation, and the release of extracellular vesicles still occurred, which may have implications for transfusion recipients. Although an optimised method is still needed, IFC has proved to be specific and potentially appropriate for detecting extracellular vesicles in transfusion preparations. Full article
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22 pages, 6808 KiB  
Article
Characterization and Hemocompatibility of α, β, and γ Cyclodextrin-Modified Magnetic Nano-Adsorbents
by Mehdi Ghaffari Sharaf, Shuhui Li, Elyn M. Rowe, Dana V. Devine and Larry D. Unsworth
Int. J. Mol. Sci. 2024, 25(19), 10710; https://doi.org/10.3390/ijms251910710 - 4 Oct 2024
Cited by 4 | Viewed by 1657
Abstract
Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can [...] Read more.
Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can be chemically modified to enhance toxin capture and the ability to be easily collected from the blood using an external magnetic field. Cyclodextrins (CDs) present a chemical structure that facilitates the binding of small molecules. However, the hemocompatibility of MNPs modified with films composed of different native types of CDs (α, β, or γ) has not yet been investigated, which is information crucial to the potential clinical application of MNPs to supplement hemodialysis. To this end, films of α-, β-, or γ-CDs were formed on MNPs and characterized. The impact of these films on the adsorbed protein structure, composition of key adsorbed proteins, and clotting kinetics were evaluated. It was found that modified MNPs did not significantly affect the secondary structure of some proteins (albumin, lysozyme, α-lactalbumin). The adsorbed proteome from platelet-poor human plasma was evaluated as a function of film properties. Compared to non-modified nanoparticles, CD-modified MNPs exhibited a significant decrease in the adsorbed protein per surface area of MNPs. The immunoblot results showed variations in the adsorption levels of C3, fibrinogen, antithrombin, Factor XI, and plasminogen across CD-modified MNPs. The hemocompatibility experiments showed that CD-modified MNPs are compatible with human whole blood, with no significant impact on platelet activation, hemolysis, or hemostasis. Full article
(This article belongs to the Special Issue Molecular Research on Nanotoxicology)
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19 pages, 59613 KiB  
Article
Tailoring Zinc Oxide Nanoparticles via Microwave-Assisted Hydrothermal Synthesis for Enhanced Antibacterial Properties
by Irina Elena Doicin, Manuela Daniela Preda, Ionela Andreea Neacsu, Vladimir Lucian Ene, Alexandra Catalina Birca, Bogdan Stefan Vasile and Ecaterina Andronescu
Appl. Sci. 2024, 14(17), 7854; https://doi.org/10.3390/app14177854 - 4 Sep 2024
Cited by 2 | Viewed by 2630
Abstract
In recent years, significant advancements in nanotechnology have facilitated the synthesis of zinc oxide (ZnO) nanoparticles with tailored sizes and shapes, offering versatile applications across various fields, particularly in biomedicine. ZnO’s multifunctional properties, such as semiconductor behavior, luminescence, photocatalytic activity, and antibacterial efficacy, [...] Read more.
In recent years, significant advancements in nanotechnology have facilitated the synthesis of zinc oxide (ZnO) nanoparticles with tailored sizes and shapes, offering versatile applications across various fields, particularly in biomedicine. ZnO’s multifunctional properties, such as semiconductor behavior, luminescence, photocatalytic activity, and antibacterial efficacy, make it highly attractive for biomedical applications. This study focuses on synthesizing ZnO nanoparticles via the microwave-assisted hydrothermal method, varying the precursor concentrations (0.3488 mol/L, 0.1744 mol/L, 0.0872 mol/L, 0.0436 mol/L, and 0.0218 mol/L) and reaction times (15, 30, and 60 min). Characterization techniques, including X-ray diffraction, scanning electron microscopy, transmission electron microscopy, BET surface area analysis, and Fourier transform infrared spectroscopy were employed to assess the structural, morphological, and chemical properties. The predominant morphology is observed to be platelets, which exhibit a polygonal shape with beveled corners and occasionally include short rod-like inserts. The thickness of the platelets varies between 10 nm and 50 nm, increasing with the concentration of Zn2+ in the precursor solution. Preliminary antimicrobial studies indicated that all strains (S. aureus, E. coli, and C. albicans) were sensitive to interaction with ZnO, exhibiting inhibition zone diameters greater than 10 mm, particularly for samples with lower precursor concentrations. Cell viability studies on human osteoblast cells demonstrated good compatibility, affirming the potential biomedical applicability of synthesized ZnO nanoparticles. This research underscores the influence of synthesis parameters on the properties of ZnO nanoparticles, offering insights for optimizing their design for biomedical applications. Full article
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15 pages, 1573 KiB  
Review
Quantum Dot Imaging Agents: Haematopoietic Cell Interactions and Biocompatibility
by Leigh Naylor-Adamson, Thomas W. Price, Zoe Booth, Graeme J. Stasiuk and Simon D. J. Calaminus
Cells 2024, 13(4), 354; https://doi.org/10.3390/cells13040354 - 18 Feb 2024
Cited by 6 | Viewed by 2781
Abstract
Quantum dots (QDs) are semi-conducting nanoparticles that have been developed for a range of biological and non-biological functions. They can be tuned to multiple different emission wavelengths and can have significant benefits over other fluorescent systems. Many studies have utilised QDs with a [...] Read more.
Quantum dots (QDs) are semi-conducting nanoparticles that have been developed for a range of biological and non-biological functions. They can be tuned to multiple different emission wavelengths and can have significant benefits over other fluorescent systems. Many studies have utilised QDs with a cadmium-based core; however, these QDs have since been shown to have poor biological compatibility. Therefore, other QDs, such as indium phosphide QDs, have been developed. These QDs retain excellent fluorescent intensity and tunability but are thought to have elevated biological compatibility. Herein we discuss the applicability of a range of QDs to the cardiovascular system. Key disease states such as myocardial infarction and stroke are associated with cardiovascular disease (CVD), and there is an opportunity to improve clinical imaging to aide clinical outcomes for these disease states. QDs offer potential clinical benefits given their ability to perform multiple functions, such as carry an imaging agent, a therapy, and a targeting motif. Two key cell types associated with CVD are platelets and immune cells. Both cell types play key roles in establishing an inflammatory environment within CVD, and as such aid the formation of pathological thrombi. However, it is unclear at present how and with which cell types QDs interact, and if they potentially drive unwanted changes or activation of these cell types. Therefore, although QDs show great promise for boosting imaging capability, further work needs to be completed to fully understand their biological compatibility. Full article
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14 pages, 8151 KiB  
Article
The Effect of Plasma Treatment on the Mechanical and Biological Properties of Polyurethane Artificial Blood Vessel
by Cheng Ding, Jing Ma, Yingxue Teng and Shanshan Chen
Materials 2023, 16(22), 7231; https://doi.org/10.3390/ma16227231 - 19 Nov 2023
Cited by 6 | Viewed by 2051
Abstract
In recent years, the incidence of cardiovascular disease has increased annually, and the demand for artificial blood vessels has been increasing. Due to the formation of thrombosis and stenosis after implantation, the application of many materials in the human body has been inhibited. [...] Read more.
In recent years, the incidence of cardiovascular disease has increased annually, and the demand for artificial blood vessels has been increasing. Due to the formation of thrombosis and stenosis after implantation, the application of many materials in the human body has been inhibited. Therefore, the choice of surface modification process is very important. In this paper, small-diameter polyurethane artificial blood vessels were prepared through electrospinning, and their surfaces were treated with plasma to improve their biological properties. The samples before and after plasma treatment were characterized by SEM, contact angle, XPS, and tensile testing; meanwhile, the cell compatibility and blood compatibility were evaluated. The results show that there are no significant changes to the fiber morphology or diameter distribution on the surface of the sample before and after plasma treatment. Plasma treatment can increase the proportion of oxygen-containing functional groups on the surface of the sample and improve its wettability, thereby increasing the infiltration ability of cells and promoting cell proliferation. Plasma treatment can reduce the risk of hemolysis, and does not cause platelet adhesion. Due to the etching effect of plasma, the mechanical properties of the samples decreased with the extension of plasma treatment time, which should be used as a basis to balance the mechanical property and biological property of artificial blood vessels. But on the whole, plasma treatment has positive significance for improving the comprehensive performance of samples. Full article
(This article belongs to the Special Issue Feature Paper in the Section 'Polymeric Materials' (2nd Edition))
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15 pages, 4994 KiB  
Article
Clinical Trial on the Safety and Tolerability of Personalized Cancer Vaccines Using Human Platelet Lysate-Induced Antigen-Presenting Cells
by Terutsugu Koya, Kenichi Yoshida, Misa Togi, Yo Niida, Sumihito Togi, Hiroki Ura, Shuichi Mizuta, Tomohisa Kato, Sohsuke Yamada, Takeo Shibata, Yi-Chang Liu, Shyng-Shiou Yuan, Deng-Chyang Wu, Hirohito Kobayashi, Taiju Utsugisawa, Hitoshi Kanno and Shigetaka Shimodaira
Cancers 2023, 15(14), 3627; https://doi.org/10.3390/cancers15143627 - 14 Jul 2023
Viewed by 2609
Abstract
Research and development of personalized cancer vaccines as precision medicine are ongoing. We predicted human leukocyte antigen (HLA)-compatible cancer antigen candidate peptides based on patient-specific cancer genomic profiles and performed a Phase I clinical trial for the safety and tolerability of cancer vaccines [...] Read more.
Research and development of personalized cancer vaccines as precision medicine are ongoing. We predicted human leukocyte antigen (HLA)-compatible cancer antigen candidate peptides based on patient-specific cancer genomic profiles and performed a Phase I clinical trial for the safety and tolerability of cancer vaccines with human platelet lysate-induced antigen-presenting cells (HPL-APCs) from peripheral monocytes. Among the five enrolled patients, two patients completed six doses per course (2–3 × 107 cells per dose), and an interim analysis was performed based on the immune response. An immune response was detected by enzyme-linked immunosorbent spot (ELISpot) assays to HLA-A*33:03-matched KRASWT, HLA-DRB1*09:01-compliant KRASWT or G12D, or HLA-A*31:01-matched SMAD4WT, and HLA-DRB1*04:01-matched SMAD4G365D peptides in two completed cases, respectively. Moreover, SMAD4WT-specific CD8+ effector memory T cells were amplified. However, an attenuation of the acquired immune response was observed 6 months after one course of cancer vaccination as the disease progressed. This study confirmed the safety and tolerability of HPL-APCs in advanced and recurrent cancers refractory to standard therapy and is the first clinical report to demonstrate the immunoinducibility of personalized cancer vaccines using HPL-APCs. Phase II clinical trials to determine immune responses with optimized adjuvant drugs and continued administration are expected to demonstrate efficacy. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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21 pages, 8807 KiB  
Article
Preparation of Hyflon AD/Polypropylene Blend Membrane for Artificial Lung
by Jie Li, Ting He, Hongyu Chen, Yangming Cheng, Enrico Drioli, Zhaohui Wang and Zhaoliang Cui
Membranes 2023, 13(7), 665; https://doi.org/10.3390/membranes13070665 - 14 Jul 2023
Cited by 6 | Viewed by 2148
Abstract
A high-performance polypropylene hollow fiber membrane (PP-HFM) was prepared by using a binary environmentally friendly solvent of polypropylene as the raw material, adopting the thermally induced phase separation (TIPS) method, and adjusting the raw material ratio. The binary diluents were soybean oil (SO) [...] Read more.
A high-performance polypropylene hollow fiber membrane (PP-HFM) was prepared by using a binary environmentally friendly solvent of polypropylene as the raw material, adopting the thermally induced phase separation (TIPS) method, and adjusting the raw material ratio. The binary diluents were soybean oil (SO) and acetyl tributyl citrate (ATBC). The suitable SO/ATBC ratio of 7/3 was based on the size change of the L-L phase separation region in PP-SO/ATBC thermodynamic phase diagram. Through the characterization and comparison of the basic performance of PP-HFMs, it was found that with the increase of the diluent content in the raw materials, the micropores of outer surface of the PP-HFM became larger, and the cross section showed a sponge-like pore structure. The fluoropolymer, Hyflon ADx, was deposited on the outer surface of the hollow fiber membrane using a physical modification method of solution dipping. After modification, the surface pore size of the Hyflon AD40L modified membranes decreased; the contact angle increased to around 107°; the surface energy decreased to 17 mN·m−1; and the surface roughness decreased to 17 nm. Hyflon AD40L/PP-HFMs also had more water resistance properties from the variation of wetting curve. For biocompatibility of the membrane, the adsorption capacity of the modified PP membrane for albumin decreased from approximately 1.2 mg·cm−2 to 1.0 mg·cm−2, and the adsorption of platelets decreased under fluorescence microscopy. The decrease in blood cells and protein adsorption in the blood prolonged the clotting time. In addition, the hemolysis rate of modified PP membrane was reduced to within the standard of 5%, and the cell survival rate of its precipitate was above 100%, which also indicated the excellent biocompatibility of fluoropolymer modified membrane. The improvement of hydrophobicity and blood compatibility makes Hyflon AD/PP-HFMs have the potential for application in membrane oxygenators. Full article
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8 pages, 1132 KiB  
Communication
Role of Nitric Oxide in the Altered Calcium Homeostasis of Platelets from Rats with Biliary Cirrhosis
by Masoud Akbari Aghdam, Paola Romecín, Joaquín García-Estañ and Noemí M. Atucha
Int. J. Mol. Sci. 2023, 24(13), 10948; https://doi.org/10.3390/ijms241310948 - 30 Jun 2023
Cited by 1 | Viewed by 1364
Abstract
Introduction: Previously, we found that intracellular calcium (Ca2+) homeostasis is altered in platelets from an experimental model of liver cirrhosis, namely the bile-duct-ligated (BDL) rat. These alterations are compatible with the existence of a hypercoagulable state. Objective: In the present study, [...] Read more.
Introduction: Previously, we found that intracellular calcium (Ca2+) homeostasis is altered in platelets from an experimental model of liver cirrhosis, namely the bile-duct-ligated (BDL) rat. These alterations are compatible with the existence of a hypercoagulable state. Objective: In the present study, we analyzed the role of nitric oxide in the abnormal calcium signaling responses of an experimental cirrhosis model, the bile duct-ligated rat. Methods: Chronic treatment with L-NAME was used to inhibit NO production in a group of control and BDL animals, and the responses compared to those obtained in a control and BDL untreated group (n = 6 each). The experiments were conducted on isolated platelets loaded with fura-2, using fluorescence spectrometry. Results: Chronic treatment with L-NAME increased thrombin-induced Ca2+ release from internal stores in both control and BDL rats. However, the effect was significantly greater in the BDL rats (p < 0.05). Thrombin-induced calcium entry from the extracellular space was also elevated but at lower doses and, similarly in both control and BDL platelets, treated with the NO synthesis inhibitor. Capacitative calcium entry was also enhanced in the control platelets but not in platelets from BDL rats treated with L-NAME. Total calcium in intracellular stores was elevated in untreated platelets from BDL rats, and L-NAME pretreatment significantly (p < 0.05) elevated these values both in controls and in BDL but significantly more in the BDL rats (p < 0.05). Conclusions: Our results suggest that nitric oxide plays a role in the abnormal calcium signaling responses observed in platelets from BDL rats by interfering with the mechanism that releases calcium from the internal stores. Full article
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