Nynke Van Den Akker | Maastricht University, Faculty of Health Medicine and Life sciences (original) (raw)

Papers by Nynke Van Den Akker

ACS applied polymer materials, Mar 8, 2022

Hydrogels are interesting materials for application in biomedicine due to their outstanding prope... more Hydrogels are interesting materials for application in biomedicine due to their outstanding properties (e.g., water retention, drug release, and biocompatibility). This work evaluates two series of phosphorus-based hydrogels as potential wounddressing candidates. The materials were synthesized via free-radical polymerization of bis[2-(methacryloyloxy)ethyl] phosphate (B M E P , ≥ 7 5 w t %) w i t h (3-a c r y l a m i d o p r o p y l)trimethylammonium chloride solution (APTAC) or 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS). Due to optimized synthetic conditions, the materials displayed an unprecedented compressive elastic modulus (E′) reaching up to 0.19 MPa, which represents a 1000-fold increase compared to previously reported materials. Furthermore, the hydrogels displayed good hydrolytic and enzymatic stability, cytocompatibility using bovine fibroblasts (BFs), and drug loading/release in woundlike pH conditions. In summary, this work demonstrates the potential of phosphorusbased hydrogels as drug-eluting wound-dressing materials.

Chemical Science, 2022

Please note that technical editing may introduce minor changes to the text and/or graphics, which... more Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal's standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains.

Procedia Engineering, 2015

A sensor system for investigating (bio)degradation processes of polymers is presented. The system... more A sensor system for investigating (bio)degradation processes of polymers is presented. The system utilizes semiconductor fieldeffect sensors and is capable of monitoring the degradation process in-situ and in real-time. The degradation of the polymer poly(D,L-lactic acid) is exemplarily monitored in solutions with different pH value, pH-buffer solution containing the model enzyme lipase from Rhizomucor miehei and cell-culture medium containing supernatants from stimulated and non-stimulated THP-1-derived macrophages mimicking activation of the immune system.

Frontiers in Immunology, Aug 6, 2018

Extracellular vesicles (EV) mediated intercellular communication between monocytes and endothelia... more Extracellular vesicles (EV) mediated intercellular communication between monocytes and endothelial cells (EC) might play a major role in vascular inflammation and atherosclerotic plaque formation during cardiovascular diseases (CVD). While critical involvement of small (exosomes) and large EV (microvesicles) in CVD has recently been appreciated, the pro-and/or anti-inflammatory impact of a bulk EV (exosomes + microvesicles) on vascular cell function as well as their inflammatory capacity are poorly defined. This study aims to unravel the immunomodulatory content of EV bulk derived from control (uEV) and TNF-α induced inflamed endothelial cells (tEV) and to define their capacity to affect the inflammatory status of recipients monocytes (THP-1) and endothelial cells (HUVEC) in vitro. Here, we show that EV derived from inflamed vascular EC were readily taken up by THP-1 and HUVEC. Human inflammation antibody array together with ELISA revealed that tEV contain a pro-inflammatory profile with chemotactic mediators, including intercellular adhesion molecule (ICAM)-1, CCL-2, IL-6, IL-8, CXCL-10, CCL-5, and TNF-α as compared to uEV. In addition, EV may mediate a selective transfer of functional inflammatory mediators to their target cells and modulate them toward either pro-inflammatory (HUVEC) or anti/pro-inflammatory (THP-1) mode. Accordingly, the expression of pro-inflammatory markers (IL-6, IL-8, and ICAM-1) in tEV-treated HUVEC was increased. In the case of THP-1, EC-EV do induce a mixed of pro-and anti-inflammatory response as indicated by the elevated expression of ICAM-1, CCL-4, CCL-5, and CXCL-10 proteins. At the functional level, EC-EV mediated inflammation and promoted the adhesion and migration of THP-1. Taken together, our findings proved that the EV released from inflamed EC were enriched with a cocktail of inflammatory markers, chemokines, and cytokines which are able to establish a targeted cross-talk between EC and monocytes and reprogramming them toward a pro-or antiinflammatory phenotypes.

The FASEB Journal, Apr 1, 2010

Advanced Science, Dec 16, 2022

Journal of Extracellular Vesicles, 2020

ABSTRACTSubstantial research has been devoted to discovering the translational potential of extra... more ABSTRACTSubstantial research has been devoted to discovering the translational potential of extracellular vesicles (EV) as a reliable liquid biopsy in the diagnosis and monitoring of several life‐affecting diseases, including chronic inflammatory diseases (CID). So far, the role of EV in the development of CID remains largely unknown due to the lack of specific tools to separate the disease‐associated EV subtypes. Therefore, this study aims to fractionate inflammation‐associated EV (sub)populations using a two‐step separation strategy based on their size combined with a specific inflammatory marker (ICAM‐1) and to unravel their proteome signature and functional integrity at the onset of vascular inflammation.Here, we report that vascular endothelial cells upon inflammation release two heterogeneous size‐based populations of EV (EV‐10 K and EV‐110 K) sharing a cocktail of inflammatory proteins, chemokines, and cytokines (chiefly: ICAM‐1, CCL‐2, CCL‐4, CCL‐5, IL‐8 and CXCL‐10). The co...

Reproductive Sciences, 2008

Increased nuchal translucency (NT), morphologically known as nuchal edema, is an ultrasound marke... more Increased nuchal translucency (NT), morphologically known as nuchal edema, is an ultrasound marker for aneuploidy. Turner syndrome presents with massive NT, called cystic hygroma. Conflicting data exist as to whether cystic hygroma and increased NT are different entities. Both are associated with jugular lymphatic distension. The authors investigated jugular lymphatics of trisomy 21, Turner syndrome, and normal karyotype fetuses. Fetuses were investigated using immunohistochemistry for blood vascular, lymphatic, and smooth muscle cell markers. Trisomy 21 fetuses showed nuchal cavities within the mesenchymal edema negative for endothelial markers. These were extremely large in Turner fetuses, showing similar characteristics. The skin showed numerous dilated lymphatics in the case of trisomy 21 and scanty small lymphatics in Turner fetuses. A jugular lymphatic sac was present in control and trisomy 21 fetuses and was enlarged in trisomy 21 cases. In Turner fetuses, no jugular lymphatic sac was observed. Nuchal edema in trisomy 21 and Turner syndrome appears to be a similar entity caused by different lymphatic abnormalities.

Circulation Research, Mar 18, 2005

The proepicardial organ provides differentiated cell types to the myocardial wall and facilitates... more The proepicardial organ provides differentiated cell types to the myocardial wall and facilitates coronary development. Ingrowth of the coronary arteries into the aorta has recently been linked to apoptosis. This study was set up to examine the effect of an inhibition of epicardial outgrowth on apoptotic patterning and coronary development. Epicardial outgrowth was blocked at HH15-17 in quail embryos, which survived until HH25-35 (nϭ33). Embryos with complete inhibition of outgrowth did not survive after HH29. These embryos presented with thin compact myocardium, devoid of vessels. In embryos with delayed epicardial outgrowth the phenotype was less severe, and surviving embryos were studied up to HH35. In these embryos, myocardial vascularization was poor and apoptosis in the peritruncal region at HH30 was diminished. Embryos at HH35 displayed an abnormal coronary network and absent coronary orifices. In a further set of experiments (nϭ10), outgrowth was inhibited in chicken embryos at HH15, followed by transplantation of a quail proepicardial organ into the pericardial cavity to rescue cardiac phenotype. These chimeras were studied at HH29 and HH35. Myocardial development was restored; however, in 3 of 4 embryos (HH35), the coronary orifices were absent. Examination of double stainings of quail-chicken chimeras revealed that EPDCs produce Fas ligand as an apoptotic inductor at sites of coronary ingrowth. In the absence of proper timing of epicardial outgrowth, myocardial development and vascularization are disturbed. Also apoptosis in the peritruncal region is diminished. During later development, this leads to defective or absent connections of the coronary system to the systemic circulation.

Macromolecular Bioscience, 2019

Hydrogel Given the major structural role phosphodiesters play in the organism it is surprising th... more Hydrogel Given the major structural role phosphodiesters play in the organism it is surprising they have not been more widely adopted as a building block in sophisticated biomimetic hydrogels and other biomaterials. The potential benefits are substantial: phosphoester-based materials show excellent compatibility with blood, cells, and a remarkable resistance to protein adsorption that may trigger a foreign-body response. In this work, a novel class of phosphodiester-based ionic hydrogels is presented which are crosslinked via a phosphodiester moiety. The material shows good compatibility with blood, supports the growth and proliferation of tissue and presents opportunities for use as a drug release matrix as shown with fluorescent model compounds. The final gel is produced via base-induced elimination from a phosphotriester precursor, which is made by the free-radical polymerization of a phosphotriester crosslinker. This crosslinker is easily synthesized via multigram one-pot procedures out of common laboratory chemicals. Via the addition of various comonomers the properties of the final gel may be tuned leading to a wide range of novel applications for this exciting class of materials.

The FASEB Journal, 2007

Notch signaling plays an important role in arterial-venous specification during embryogenesis. Ho... more Notch signaling plays an important role in arterial-venous specification during embryogenesis. However, the role of Notch signaling in lymphatic development is poorly understood. Here, we show that...

Atherosclerosis Supplements, 2011

Scientific reports, May 8, 2017

An expansive collateral artery network is correlated with improved survival in case of adverse ca... more An expansive collateral artery network is correlated with improved survival in case of adverse cardiac episodes. We aimed to identify cellular microRNAs (miRNA; miR) important for collateral artery growth. Chronic total occlusion (CTO) patients (n = 26) were dichotomized using pressure-derived collateral flow index (CFIp) measurements; high collateral capacity (CFIp > 0.39; n = 14) and low collateral (CFIp < 0.39; n = 12) capacity. MiRNA profiling via next generation sequencing from various monocyte phenotypes (freshly isolated monocytes, monocytes cultured without stimulant, or stimulation with lipopolysaccharide, interleukin 4, transforming growth factor beta-1, or interferon gamma) revealed significantly different miRNA expression patterns between high versus low collateral capacity patients. Validation by real-time polymerase chain reaction demonstrated significantly decreased expression of miR339-5p in all stimulated monocyte phenotypes of low collateral capacity patients...

Nanomedicine : nanotechnology, biology, and medicine, Jan 30, 2017

A major conceptual breakthrough in cell signaling has been the finding of EV as new biomarker shu... more A major conceptual breakthrough in cell signaling has been the finding of EV as new biomarker shuttles in body fluids. Now, one of the major challenges in using these nanometer-sized biological entities as diagnostic marker is the development of translational methodologies to profile them. SPR offers a promising label-free and real time platform with a high potential for biomarker detection. Therefore, we aimed to develop a uniform SPR methodology to detect specific surface markers on EV derived from patient with CHD. EVs having an approximate size range between 30 and 100 nm (~48.5%) and 100-300 nm (~51.5%) were successfully isolated. The biomarker profile of EV was verified using immunogold labeling, ELISA and SPR. Using SPR, we demonstrated an increased binding of EV derived from patients with CHD to anti-ICAM-1 antibodies as compared to EV from healthy donors. Our current findings open up novel opportunities for in-depth and label-free investigation of EV.

International journal of pharmaceutics, Jan 30, 2016

Poly(d,l-lactic acid) biodegradable microspheres, loaded with the drugs cisplatin and/or sorafeni... more Poly(d,l-lactic acid) biodegradable microspheres, loaded with the drugs cisplatin and/or sorafenib tosylate, were prepared, characterized and studied. Degradation of the microspheres, and release of cisplatin and/or sorafenib tosylate from them, were investigated in detail. Incubation of the drug-carrying microspheres in phosphate buffered saline (pH=7.4) revealed slow degradation. Nevertheless, significant release of cisplatin and sorafenib tosylate from microspheres loaded with both drugs was apparent in vitro; this can be attributed to their porous structure. Supernatants from microspheres loaded with both drugs showed strong toxic effects on cells (i.e. endothelial cells, fibroblast cells and Renca tumor cells) and potent anti-angiogenic effect in the matrigel endothelial tube assay. In vivo anti-tumor effects of the microspheres were also observed, in a Renca tumor mouse model. The poly(d,l-lactic acid) microspheres containing both cisplatin and sorafenib tosylate revealed high...

Journal of Vascular Research

Introduction Imaging and visualization of Nitric Oxide (NO), an important messenger that regulate... more Introduction Imaging and visualization of Nitric Oxide (NO), an important messenger that regulates a multitude of function within the vascular system, is essential to better define its role in (patho)physiology. We study a novel NO-sensitive copper-fluorescein complex (CuFL) with two-photon laser scanning microscopy (TPLSM). Methods To study cellular NO production both in vitro and ex vivo CuFL fluorescence was determined using TPLSM. CuFL was characterized and compared with DAF-2-DA. In endothelial cell (EC) cultures, hydrogen peroxide (H2O2 ), acetylcholine and shear stress were used as stimulant. Isolated murine carotid arteries were incubated ex vivo with H2O2 and acetylcholine to stimulate NO production. Isolated arteries were mounted in a home-built perfusion chamber and transmural pressure was applied to mimic physiological condition. Endothelium functional capacity of artery, that depends on the amount of NO produced and the vasodilatation effect was evaluated by measuring l...

Wiener klinische Wochenschrift, 2007

Pediatric Cardiology, 2014

The degree of right ventricular outflow tract obstruction, pulmonary stenosis (PS) and the develo... more The degree of right ventricular outflow tract obstruction, pulmonary stenosis (PS) and the development of major aorto-pulmonary collateral arteries (MAPCAs) in patients with tetralogy of Fallot (TOF) is related to clinical outcome. Vegf120/120 mutant mouse embryos develop TOF with various degrees of PS, comparable to humans. We aimed to study the ontogeny of the development of MAPCAs in this mouse model. The development of the right ventricular outflow tract, pulmonary arteries, and ductus arteriosus (DA) and formation of MAPCAs were studied in both wild type as well as Vegf120/120 mice from embryonic day 10.5 until day 19.5. Of the 49 Vegf120/120 embryos, 35 embryos (71 %) had ventral displacement of the outflow tract and a subaortic ventricular septal defect. A time-related development in severity of PS to pulmonary atresia (PA) was observed. From embryonic day 12.5, hypoplasia of the DA was seen in 13 (37 %) and absent DA in 12 (37 %) of these embryos. The 3 (6 %) embryos with PA and absent DA developed MAPCAs, after day 15.5. In all, the MAPCAs arose from both subclavian arteries, running posterior in the thoracic cavity, along the vagal nerve. The MAPCAs connected the pulmonary arteries at the site of the hilus. A time-related development of PS to PA can lead, in combination with absent DA, to the development of MAPCAs later in embryonic life as an alternative route for pulmonary perfusion in this mouse model. This finding contributes to a better understanding of the consecutive morphological changes in the development toward MAPCAs in humans.