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1.
MRS Commun ; : 1-9, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34513262

RESUMO

In vitro thrombogenicity test systems require co-cultivation of endothelial cells and platelets under blood flow-like conditions. Here, a commercially available perfusion system is explored using plasma-treated cyclic olefin copolymer (COC) as a substrate for the endothelial cell layer. COC was characterized prior to endothelialization and co-cultivation with platelets under static or flow conditions. COC exhibits a low roughness and a moderate hydrophilicity. Flow promoted endothelial cell growth and prevented platelet adherence. These findings show the suitability of COC as substrate and the importance of blood flow-like conditions for the assessment of the thrombogenic risk of drugs or cardiovascular implant materials. Supplementary Information: The online version contains supplementary material available at 10.1557/s43579-021-00072-6.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34420942

RESUMO

BACKGROUND: Type two diabetes mellitus (T2DM) patients are prone to develop atherothrombotic events due to platelet hyper-reactivity stemming from platelet miRNA-223 down-regulation and over-expression of its corresponding target, P2RY12. OBJECTIVE: The study sought to determine the effects of long-term aerobic training on the expression levels of miRNA-223 and P2RY12 mRNA, and platelet function in T2DM patients. METHODS: Twenty-four patients with T2DM (age, 60.0±2.8 yrs.) were selected and randomly divided into two groups: aerobic exercise training (AET, n = 12) and control (CON, n = 12). The AET protocol was performed with moderate intensity for 12 weeks, while patients in the CON group followed their usual routine. Weight, body mass index (BMI), peak oxygen consumption (VO2peak), lipid profile, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), platelet miRNA-223 and P2RY12 expression were measured before and after the period. RESULTS: There was a significant improvement in body weight, BMI, VO2peak, FBG, HbA1c, and HOMA-IR, after 12 weeks of AET (P <  0.01). Platelet aggregation decreased significantly after 12 weeks in the AET group compared with the CON (P <  0.001) group. Platelets' miRNA-223 and P2RY12 were significantly up- and down-regulated after AET in comparison with the CON group (P <  0.05), respectively. Moreover, the relative expression of miRNA-223 and P2RY12 significantly correlated with FBG changes following the intervention. CONCLUSIONS: It can be concluded that long-term moderate-intensity aerobic training might be effective for reducing the occurrence of atherothrombotic events leading to premature death in T2DM patients through the modulation of miRNA-223, P2RY12 receptor expression, and platelet function.

3.
Life (Basel) ; 11(6)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207508

RESUMO

Arthrospira platensis (AP) is a cyanobacterium with a high economic value and is nowadays one of the most important industrially cultivated microalgae. Knowledge of its growth is essential for the understanding of its physiology and yield. The growth of AP biomass occurs through two mechanisms: (1) propagation by fragmentation of trichomes, and (2) the trichomes are extended by binary fission until they reach their mature status. These phases are visualized by live cell light and laser scanning microscopy, demonstrating the different phases of AP growth.

4.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209789

RESUMO

Near-physiological in vitro thrombogenicity test systems for the evaluation of blood-contacting endothelialized biomaterials requires co-cultivation with platelets (PLT). However, the addition of PLT has led to unphysiological endothelial cell (EC) detachment in such in vitro systems. A possible cause for this phenomenon may be PLT activation triggered by the applied endothelial cell medium, which typically consists of basal medium (BM) and nine different supplements. To verify this hypothesis, the influence of BM and its supplements was systematically analyzed regarding PLT responses. For this, human platelet rich plasma (PRP) was mixed with BM, BM containing one of nine supplements, or with BM containing all supplements together. PLT adherence analysis was carried out in six-channel slides with plasma-treated cyclic olefin copolymer (COC) and poly(tetrafluoro ethylene) (PTFE, as a positive control) substrates as part of the six-channel slides in the absence of EC and under static conditions. PLT activation and aggregation were analyzed using light transmission aggregometry and flow cytometry (CD62P). Medium supplements had no effect on PLT activation and aggregation. In contrast, supplements differentially affected PLT adherence, however, in a polymer- and donor-dependent manner. Thus, the use of standard endothelial growth medium (BM + all supplements) maintains functionality of PLT under EC compatible conditions without masking the differences of PLT adherence on different polymeric substrates. These findings are important prerequisites for the establishment of a near-physiological in vitro thrombogenicity test system assessing polymer-based cardiovascular implant materials in contact with EC and PLT.


Assuntos
Materiais Biocompatíveis/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Meios de Cultura/farmacologia , Adulto , Materiais Biocompatíveis/química , Plaquetas/citologia , Meios de Cultura/química , Endotélio/citologia , Feminino , Humanos , Masculino , Teste de Materiais , Pessoa de Meia-Idade , Ativação Plaquetária/efeitos dos fármacos , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Polímeros/farmacologia , Tecidos Suporte/química
5.
Life (Basel) ; 11(2)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513794

RESUMO

The application of cytostatic drugs or natural substances to inhibit cancer growth and progression is an important and evolving subject of cancer research. There has been a surge of interest in marine bioresources, particularly algae, as well as cyanobacteria and their bioactive ingredients. Dried biomass products of Arthrospira and Chlorella have been categorized as "generally recognized as safe" (GRAS) by the US Food and Drug Administration (FDA). Of particular importance is an ingredient of Arthrospira: phycocyanin, a blue-red fluorescent, water-soluble and non-toxic biliprotein pigment. It is reported to be the main active ingredient of Arthrospira and was shown to have therapeutic properties, including anti-oxidant, anti-inflammatory, immune-modulatory and anti-cancer activities. In the present review, in vitro and in vivo data on the effects of phycocyanin on various tumor cells and on cells from healthy tissues are summarized. The existing knowledge of underlying molecular mechanisms, and strategies to improve the efficiency of potential phycocyanin-based anti-cancer therapies are discussed.

6.
Int J Mol Sci ; 21(23)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33260972

RESUMO

Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. In this review, we focus on their influence on platelets, which are key elements in thrombosis and hemostasis. The function of platelets is influenced by mediators in the blood and the vascular wall. Activated platelets aggregate and release bioactive substances, thereby activating further neighbored platelets, which finally can lead to the formation of thrombi. Prostanoids regulate the function of blood platelets by both activating or inhibiting and so are involved in hemostasis. Each prostanoid has a unique activity profile and, thus, a specific profile of action. This article reviews the effects of the following prostanoids: prostaglandin-D2 (PGD2), prostaglandin-E1, -E2 and E3 (PGE1, PGE2, PGE3), prostaglandin F2α (PGF2α), prostacyclin (PGI2) and thromboxane-A2 (TXA2) on platelet activation and aggregation via their respective receptors.


Assuntos
Plaquetas/fisiologia , Prostaglandinas/farmacologia , Plaquetas/efeitos dos fármacos , Humanos , Modelos Biológicos , Agregação Plaquetária/efeitos dos fármacos , Receptores de Prostaglandina/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
Adv Healthc Mater ; 8(21): e1900527, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31612646

RESUMO

The short- and long-term thrombogenicity of implant materials is still unpredictable, which is a significant challenge for the treatment of cardiovascular diseases. A knowledge-based approach for implementing biofunctions in materials requires a detailed understanding of the medical device in the biological system. In particular, the interplay between material and blood components/cells as well as standardized and commonly acknowledged in vitro test methods allowing a reproducible categorization of the material thrombogenicity requires further attention. Here, the status of in vitro thrombogenicity testing methods for biomaterials is reviewed, particularly taking in view the preparation of test materials and references, the selection and characterization of donors and blood samples, the prerequisites for reproducible approaches and applied test systems. Recent joint approaches in finding common standards for a reproducible testing are summarized and perspectives for a more disease oriented in vitro thrombogenicity testing are discussed.


Assuntos
Anticoagulantes/química , Materiais Biocompatíveis/química , Anticoagulantes/farmacologia , Materiais Biocompatíveis/farmacologia , Plaquetas/efeitos dos fármacos , Feminino , Hemólise/efeitos dos fármacos , Humanos , Masculino , Teste de Materiais
8.
Acta Biomater ; 87: 55-60, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30660001

RESUMO

From stents and large-diameter vascular grafts, to mechanical heart valves and blood pumps, blood-contacting devices are enjoying significant clinical success owing to the application of systemic antiplatelet and anticoagulation therapies. On the contrary, research into material and device hemocompatibility aimed at alleviating the need for systemic therapies has suffered a decline. This research area is undergoing a renaissance fueled by recent fundamental insights into coagulation and inflammation that are offering new avenues of investigation, the growing recognition of the limitations facing existing therapeutic approaches, and the severity of the cardiovascular disorders epidemic. This Opinion article discusses clinical needs for hemocompatible materials and the emerging research directions for fulfilling those needs. Based on the 2017 BloodSurf conference that brought together clinicians, scientists, and engineers from academia, industry, and regulatory bodies, its purpose is to draw the attention of the wider clinical and scientific community to stimulate further growth. STATEMENT OF SIGNIFICANCE: The article highlights recent fundamental insights into coagulation, inflammation, and blood-biomaterial interactions that are fueling a renaissance in the field of material hemocompatibility. It will be useful for clinicians, scientists, engineers, representatives of industry and regulatory bodies working on the problem of developing hemocompatible materials and devices for treating cardiovascular disorders.


Assuntos
Coagulação Sanguínea , Prótese Vascular , Próteses Valvulares Cardíacas , Teste de Materiais , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Humanos , Stents
9.
Clin Hemorheol Microcirc ; 71(2): 183-191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30584128

RESUMO

Circulating blood cells are prone to varying flow conditions when contacting cardiovascular devices. For a profound understanding of the complex interplay between the blood components/cells and cardiovascular implant surfaces, testing under varying shear conditions is required. Here, we study the influence of arterial and venous shear conditions on the in vitro evaluation of the thrombogenicity of polymer-based implant materials.Medical grade poly(dimethyl siloxane) (PDMS), polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) films were included as reference materials. The polymers were exposed to whole blood from healthy humans. Blood was agitated orbitally at low (venous shear stress: 2.8 dyne · cm-2) and high (arterial shear stress: 22.2 dyne · cm-2) agitation speeds in a well-plate based test system. Numbers of non-adherent platelets, platelet activation (P-Selectin positive platelets), platelet function (PFA100 closure times) and platelet adhesion (laser scanning microscopy (LSM)) were determined.Microscopic data and counting of the circulating cells revealed increasing numbers of material-surface adherent platelets with increasing agitation speed. Also, activation of the platelets was substantially increased when tested under the high shear conditions (P-Selectin levels, PFA-100 closure times). At low agitation speed, the platelet densities did not differ between the three materials. Tested at the high agitation speed, lowest platelet densities were observed on PDMS, intermediate levels on PET and highest on PTFE. While activation of the circulating platelets was affected by the implant surfaces in a similar manner, PFA closure times did not reflect this trend.Differences in the thrombogenicity of the studied polymers were more pronounced when tested at high agitation speed due to the induced shear stresses. Testing under varying shear stresses, thus, led to a different evaluation of the implant thrombogenicity, which emphasizes the need for testing under various flow conditions. Our data further confirmed earlier findings where the same reference implants were tested under static (and not dynamic) conditions and with fresh human platelet rich plasma instead of whole blood. This supports that the application of common reference materials may improve inter-study comparisons, even under varying test conditions.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Ativação Plaquetária/fisiologia , Adesividade Plaquetária/fisiologia , Humanos , Estresse Mecânico
12.
Blood Rev ; 31(1): 11-21, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27478147

RESUMO

There is a widely recognized need to improve the performance of vascular implants and external medical devices that come into contact with blood by reducing adverse reactions they cause, such as thrombosis and inflammation. These reactions lead to major adverse cardiovascular events such as heart attacks and strokes. Currently, they are managed therapeutically. This need remains unmet by the biomaterials research community. Recognized stagnation of the blood-biomaterial interface research translates into waning interest from clinicians, funding agencies, and practitioners of adjacent fields. The purpose of this contribution is to stir things up. It follows the 2014 BloodSurf meeting (74th International IUVSTA Workshop on Blood-Biomaterial Interactions), offers reflections on the situation in the field, and a three-pronged strategy integrating different perspectives on the biological mechanisms underlying blood-biomaterial interactions. The success of this strategy depends on reengaging clinicians and on the renewed cooperation of the funding agencies to support long-term efforts.


Assuntos
Materiais Biocompatíveis , Coagulação Sanguínea , Próteses e Implantes , Animais , Materiais Biocompatíveis/normas , Materiais Biocompatíveis/uso terapêutico , Materiais Biomiméticos/normas , Materiais Biomiméticos/uso terapêutico , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/cirurgia , Testes Hematológicos , Humanos , Próteses e Implantes/efeitos adversos , Próteses e Implantes/normas
14.
Biointerphases ; 11(2): 029702, 2016 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-27277200

RESUMO

In view of the rare presence of studies concerning platelet function as risk factor in atherosclerotic patients, processes underlying thromboembolic events are reviewed in this paper. The morphology and the structural organization-membrane receptors, the open canalicular and dense tubular systems, the cytoskeleton, mitochondria, granules, lysosomes, and peroxisomes-of platelets are described. Platelet function under physiological conditions in atherosclerosis and after implantation of cardiovascular devices is summarized.


Assuntos
Plaquetas/fisiologia , Vasos Sanguíneos/patologia , Adesão Celular , Doença da Artéria Coronariana/patologia , Equipamentos e Provisões/efeitos adversos , Tromboembolia/fisiopatologia , Humanos
16.
J Mater Chem B ; 2(23): 3626-3635, 2014 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32263799

RESUMO

Hemocompatible materials are needed for internal and extracorporeal biomedical applications, which should be realizable by reducing protein and thrombocyte adhesion to such materials. Polyethers have been demonstrated to be highly efficient in this respect on smooth surfaces. Here, we investigate the grafting of oligo- and polyglycerols to rough poly(ether imide) membranes as a polymer relevant to biomedical applications and show the reduction of protein and thrombocyte adhesion as well as thrombocyte activation. It could be demonstrated that, by performing surface grafting with oligo- and polyglycerols of relatively high polydispersity (>1.5) and several reactive groups for surface anchoring, full surface shielding can be reached, which leads to reduced protein adsorption of albumin and fibrinogen. In addition, adherent thrombocytes were not activated. This could be clearly shown by immunostaining adherent proteins and analyzing the thrombocyte covered area. The presented work provides an important strategy for the development of application relevant hemocompatible 3D structured materials.

17.
Macromol Biosci ; 13(12): 1720-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24167100

RESUMO

The chain length and end groups of linear PEG grafted on smooth surfaces is known to influence protein adsorption and thrombocyte adhesion. Here, it is explored whether established structure function relationships can be transferred to application relevant, rough surfaces. Functionalization of poly(ether imide) (PEI) membranes by grafting with monoamino PEG of different chain lengths (Mn =1 kDa or 10 kDa) and end groups (methoxy or hydroxyl) is proven by spectroscopy, changes of surface hydrophilicity, and surface shielding effects. The surface functionalization does lead to reduction of adsorption of BSA, but not of fibrinogen. The thrombocyte adhesion is increased compared to untreated PEI surfaces. Conclusively, rough instead of smooth polymer or gold surfaces should be investigated as relevant models.


Assuntos
Plaquetas/efeitos dos fármacos , Fibrinogênio/química , Adesividade Plaquetária/efeitos dos fármacos , Polietilenoglicóis/química , Polímeros/química , Soroalbumina Bovina/química , Adsorção , Plaquetas/citologia , Células Cultivadas , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Microscopia Eletrônica de Varredura , Polímeros/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
18.
Clin Hemorheol Microcirc ; 54(3): 235-48, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23603330

RESUMO

Linear, side-chain methylated oligoglycerols (OGMe) were recently reported as potential surface passivating molecules for improving the protein resistance of cardiovascular application relevant poly(ether imide) (PEI) membranes. A previously reported in vitro screening under static test conditions allowed an end-point evaluation of the adhesion and activation of adherent thrombocytes performed on the material surfaces and revealed similar levels of thrombogenicity on PEI membranes, functionalized with OGMe and oligo(ethylene glycol) (OEG) of similar molecular weight (Mn = 1,300 g·mol-1 - 1,800 g·mol-1). In the present study, we investigated the hemocompatibility of these materials in a dynamic closed loop system, in order to study time-dependent thrombocyte material interactions also of the circulating thrombocytes by mimicking in vivo relevant flow conditions in a dynamic test system with multiple material contacts. Activation and aggregation of circulating thrombocytes as well as complement activation and plasmatic coagulation were evaluated after 40 circulations of thrombocyte rich plasma in the closed loop system. The results of the dynamic tests revealed no differences between the OGMe and OEG functionalized PEI membranes. Furthermore, no differences were observed between the latter and a PEI membrane treated under the conditions of functionalization at pH 11 (PEI-pH11) without an oligoether being present. Blood plasma protein adsorption, as well as activation, and adherence of circulating thrombocytes occurred in a comparable, but minor manner on all investigated PEI membranes. From this we conclude that the OGMe and OEG surface functionalization did not lead to an improvement of the already good hemocompatibility of the PEI-pH11 membrane.


Assuntos
Materiais Biocompatíveis/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Glicerol/metabolismo , Membranas Artificiais , Polietilenoglicóis/metabolismo , Polímeros/metabolismo , Materiais Biocompatíveis/química , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Ativação do Complemento/efeitos dos fármacos , Glicerol/química , Humanos , Teste de Materiais , Metilação , Ativação Plaquetária/efeitos dos fármacos , Polietilenoglicóis/química , Polímeros/química , Propriedades de Superfície
20.
Macromol Rapid Commun ; 33(17): 1487-92, 2012 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-22821898

RESUMO

Materials for biomedical applications are often chosen for their bulk properties. Other requirements such as a hemocompatible surface shall be fulfilled by suitable chemical functionalization. Here we show, that linear, side-chain methylated oligoglycerols (OGMe) are more stable to oxidation than oligo(ethylene glycol) (OEG). Poly(ether imide) (PEI) membranes functionalized with OGMes perform at least as good as, and partially better than, OEG functionalized PEI membranes in view of protein resistance as well as thrombocyte adhesion and activation. Therefore, OGMes are highly potent surface functionalizing molecules for improving the hemocompatibility of polymers.


Assuntos
Plaquetas/metabolismo , Glicerol/química , Membranas Artificiais , Polímeros/química , Adsorção , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Plaquetas/citologia , Adesão Celular , Oxirredução , Proteínas/química , Proteínas/metabolismo , Propriedades de Superfície
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