scholarly journals Fabrication of placental barrier structures within a microfluidic device utilizing two-photon polymerization

2018 ◽  
Vol 4 (2) ◽  
Author(s):  
Denise Mandt ◽  
Peter Gruber ◽  
Marica Markovic ◽  
Maximillian Tromayer ◽  
Mario Rothbauer ◽  
...  
Keyword(s):  
High Resolution ◽  
Microfluidic Device ◽  
Umbilical Vein ◽  
Transport Processes ◽  
The Body ◽  
Primary Amines ◽  
Placental Barrier ◽  
Two Photon ◽  
Two Photon Polymerization

The placenta is a transient organ, essential for development and survival of the unborn fetus. It interfaces the body of the pregnant woman with the unborn child and secures transport of endogenous and exogenous substances. Maternal and fetal blood are thereby separated at any time, by the so-called placental barrier. Current in vitro approaches fail to model this multifaceted structure, therefore research in the field of placental biology is particularly challenging. The present study aimed at establishing a novel model, simulating placental transport and its implications on development, in a versatile but reproducible way. The basal membrane was replicated using a gelatin-based material, closely mimicking the composition and properties of the natural extracellular matrix. The microstructure was produced by using a high-resolution 3D printing method – the two-photon polymerization (2PP). In order to structure gelatin by 2PP, its primary amines and carboxylic acids are modified with methacrylamides and methacrylates (GelMOD-AEMA), respectively. High-resolution structures in the range of a few micrometers were produced within the intersection of a customized microfluidic device, separating the x-shaped chamber into two isolated cell culture compartments. Human umbilical-vein endothelial cells (HUVEC) seeded on one side of this membrane simulate the fetal compartment while human choriocarcinoma cells, isolated from placental tissue (BeWo B30) mimic the maternal syncytium. This barrier model in combination with native flow profiles can be used to mimic the microenvironment of the placenta, investigating different pharmaceutical, clinical and biological scenarios. As proof-of-principle, this bioengineered placental barrier was used for the investigation of transcellular transport processes. While high molecular weight substances did not permeate, smaller molecules in the size of glucose were able to diffuse through the barrier in a time-depended manner. We envision to apply this bioengineered placental barrier for pathophysiological research, where altered nutrient transport is associated with health risks for the fetus.

scholarly journals Establishment of an in vitro placental barrier model cultured under physiologically relevant oxygen levels

2020 ◽  
Vol 26 (5) ◽  
pp. 353-365
Author(s):  
Michael K Wong ◽  
Edward W Li ◽  
Mohamed Adam ◽  
Ponnambalam R Selvaganapathy ◽  
Sandeep Raha
Keyword(s):  
Cell Layer ◽  
Umbilical Vein ◽  
The Body ◽  
Bewo Cell ◽  
Placental Barrier ◽  
Low Oxygen ◽  
Apparent Permeability ◽  
Oxygen Levels ◽  
Specific Permeability

Abstract The human placental barrier facilitates many key functions during pregnancy, most notably the exchange of all substances between the mother and fetus. However, preclinical models of the placental barrier often lacked the multiple cell layers, syncytialization of the trophoblast cells and the low oxygen levels that are present within the body. Therefore, we aimed to design and develop an in vitro model of the placental barrier that would reinstate these factors and enable improved investigations of barrier function. BeWo placental trophoblastic cells and human umbilical vein endothelial cells were co-cultured on contralateral sides of an extracellular matrix-coated transwell insert to establish a multilayered barrier. Epidermal growth factor and forskolin led to significantly increased multi-nucleation of the BeWo cell layer and increased biochemical markers of syncytial fusion, for example syncytin-1 and hCGβ. Our in vitro placental barrier possessed size-specific permeability, with 4000-Da molecules experiencing greater transport and a lower apparent permeability coefficient than 70 000-Da molecules. We further demonstrated that the BeWo layer had greater resistance to smaller molecules compared to the endothelial layer. Chronic, physiologically low oxygen exposure (3–8%) increased the expression of hypoxia-inducible factor 1α and syncytin-1, further increased multi-nucleation of the BeWo cell layer and decreased barrier permeability only against smaller molecules (457 Da/4000 Da). In conclusion, we built a novel in vitro co-culture model of the placental barrier that possessed size-specific permeability and could function under physiologically low oxygen levels. Importantly, this will enable future researchers to better study the maternal–fetal transport of nutrients and drugs during pregnancy.

Biomimicry at the nanoscale: current research and perspectives of two-photon polymerization

Nanoscale ◽  
2015 ◽  
Vol 7 (7) ◽  
pp. 2841-2850 ◽  
Author(s):  
Attilio Marino ◽  
Carlo Filippeschi ◽  
Virgilio Mattoli ◽  
Barbara Mazzolai ◽  
Gianni Ciofani
Keyword(s):  
Two Photon ◽  
Two Photon Polymerization

The most recent examples of the control of the in vitro biophysical micro/nano-environment by exploiting two-photon polymerization (2pp).

scholarly journals Electroacupuncture Reduces Oocyte Number and Maintains Vascular Barrier Against Ovarian Hyperstimulation Syndrome by Regulating CD200

2021 ◽  
Vol 9 ◽  
Author(s):  
Li Chen ◽  
Xuan Huang ◽  
Li Wang ◽  
Cencen Wang ◽  
Xu Tang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Barrier Function ◽  
Ovarian Hyperstimulation Syndrome ◽  
Umbilical Vein ◽  
Ovarian Tissue ◽  
The Body ◽  
Corpora Lutea ◽  
Ovarian Hyperstimulation ◽  
Oocyte Number

Ovarian hyperstimulation syndrome (OHSS) is a common complication caused by ovulatory stimulation therapy, which manifests as an increase in ovarian volume, an increase in the number of oocytes retrieved, and increased vascular permeability throughout the body and especially in ovarian tissue. In our previous study, we found that electroacupuncture (EA) could prevent the progression of OHSS, by mainly affecting ovary. However, the specific molecules and the mechanism of this process were still unknown. In order to explore the underlying mechanism, OHSS rat model was established and EA treatment was performed, which was followed by proteomic analysis of ovaries. Results showed a significant increase in the expression level of CD200 in the ovaries of OHSS group treated with EA than those of OHSS group. Clinical data showed that the level of CD200 in follicular fluid was negatively correlated with the number of oocytes retrieved and serum E2 level. Further in vitro experiments showed a concentration-dependent role of human chorionic gonadotropin (hCG) in reducing CD200 and CD200R levels, and increasing inflammatory cytokine levels in cultured KGN cells. In human umbilical vein endothelial cells (HUVECs), the vascular barrier function was improved by CM (cultural medium from KGN cell) which treated with CD200Fc (CD200R agonist). Meanwhile, the results of in vivo experiments indicated that EA reduced the number of ovarian corpora lutea, decreased inflammatory response, and improved the vascular barrier function by increasing the expression of CD200 and CD200R in rat ovaries. These findings suggest that EA treatment may reduce oocyte number and maintain vascular barrier against OHSS through ovarian anti-inflammatory response mediated by CD200. Therefore, this study is the first to identify CD200 as a main of EA in the ovary and elucidate the possible mechanism of EA on preventing and treating OHSS, which provide a scientific basis for CD200 as an effector and indicator in EA treatment.

scholarly journals Development of an Organ-on-a-Chip-Device for Study of Placental Pathologies

2020 ◽  
Vol 21 (22) ◽  
pp. 8755
Author(s):  
Babak Mosavati ◽  
Andrew V. Oleinikov ◽  
E. Du
Keyword(s):  
Numerical Model ◽  
Human Placenta ◽  
Umbilical Vein ◽  
Microfluidic Channels ◽  
Placental Barrier ◽  
Polycarbonate Membrane ◽  
Glucose Diffusion ◽  
Membrane Porosity ◽  
Umbilical Vein Endothelial Cells

The human placenta plays a key role in reproduction and serves as a major interface for maternofetal exchange of nutrients. Study of human placenta pathology presents a great experimental challenge because it is not easily accessible. In this paper, a 3D placenta-on-a-chip model is developed by bioengineering techniques to simulate the placental interface between maternal and fetal blood in vitro. In this model, trophoblasts cells and human umbilical vein endothelial cells are cultured on the opposite sides of a porous polycarbonate membrane, which is sandwiched between two microfluidic channels. Glucose diffusion across this barrier is analyzed under shear flow conditions. Meanwhile, a numerical model of the 3D placenta-on-a-chip model is developed. Numerical results of concentration distributions and the convection–diffusion mass transport is compared to the results obtained from the experiments for validation. Finally, effects of flow rate and membrane porosity on glucose diffusion across the placental barrier are studied using the validated numerical model. The placental model developed here provides a potentially helpful tool to study a variety of other processes at the maternal–fetal interface, for example, effects of drugs or infections like malaria on transport of various substances across the placental barrier.

3D hydrogels with high resolution fabricated by two-photon polymerization with sensitive water soluble initiators

2015 ◽  
Vol 3 (43) ◽  
pp. 8486-8491 ◽  
Author(s):  
Jinfeng Xing ◽  
Ling Liu ◽  
Xiaoyan Song ◽  
Yuanyuan Zhao ◽  
Ling Zhang ◽  
...  
Keyword(s):  
High Resolution ◽  
Spatial Resolution ◽  
Biomedical Applications ◽  
Water Soluble ◽  
Two Photon ◽  
Two Photon Polymerization

Hydrogels with precise 3D configuration are crucial for biomedical applications, which demand for the improvement of the spatial resolution on both the microscopic and the nanometric scale.

scholarly journals In-vivo vascular application via ultra-fast bioprinting for future 5D personalised nanomedicine

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ruben Foresti ◽  
Stefano Rossi ◽  
Silvana Pinelli ◽  
Rossella Alinovi ◽  
Corrado Sciancalepore ◽  
...  
Keyword(s):  
Additive Manufacturing ◽  
High Resolution ◽  
Computer Tomography ◽  
Umbilical Vein ◽  
Personalised Medicine ◽  
Vena Cava ◽  
Fluorescent Nanoparticles ◽  
Computer Tomography Scan

Abstract The design of 3D complex structures enables new correlation studies between the engineering parameters and the biological activity. Moreover, additive manufacturing technology could revolutionise the personalised medical pre-operative management due to its possibility to interplay with computer tomography. Here we present a method based on rapid freeze prototyping (RFP) 3D printer, reconstruction cutting, nano dry formulation, fast freeze gelation, disinfection and partial processes for the 5D digital models functionalisation. We elaborated the high-resolution computer tomography scan derived from a complex human peripheral artery and we reconstructed the 3D model of the vessel in order to obtain and verify the additive manufacturing processes. Then, based on the drug-eluting balloon selected for the percutaneous intervention, we reconstructed the biocompatible eluting-freeform coating containing 40 nm fluorescent nanoparticles (NPs) by means of RFP printer and we tested the in-vivo feasibility. We introduced the NPs-loaded 5D device in a rat’s vena cava. The coating dissolved in a few minutes releasing NPs which were rapidly absorbed in vascular smooth muscle cell (VSMC) and human umbilical vein endothelial cell (HUVEC) in-vitro. We developed 5D high-resolution self-dissolving devices incorporating NPs with the perspective to apply this method to the personalised medicine.

scholarly journals In vitro degradation and mechanical properties of PLA-PCL copolymer unit cell scaffolds generated by two-photon polymerization

2016 ◽  
Vol 11 (1) ◽  
pp. 015011 ◽  
Author(s):  
R M Felfel ◽  
Leander Poocza ◽  
Miquel Gimeno-Fabra ◽  
Tobias Milde ◽  
Gerhard Hildebrand ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Unit Cell ◽  
In Vitro Degradation ◽  
Two Photon ◽  
Cell Scaffolds ◽  
Two Photon Polymerization

scholarly journals 3D in vitro platform produced by two-photon polymerization for the analysis of neural network formation and function

2016 ◽  
Vol 2 (3) ◽  
pp. 035001 ◽  
Author(s):  
P S Timashev ◽  
M V Vedunova ◽  
D Guseva ◽  
E Ponimaskin ◽  
A Deiwick ◽  
...  
Keyword(s):  
Neural Network ◽  
Network Formation ◽  
Two Photon ◽  
And Function ◽  
Two Photon Polymerization
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