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3. Compartmentalized Culture of Perivascular Stroma and Endothelial Cells in a Microfluidic Model of the Human Endometrium.

Author

Gnecco, Juan S, Pensabene, Virginia, Li, David J, Ding, Tianbing, Hui, Elliot E, Bruner-Tran, Kaylon L, and Osteen, Kevin G

Subjects
Cell Culture Techniques, Endometrium: blood supply, cytology, metabolism, Female, Human Umbilical Vein Endothelial Cells: cytology, metabolism, Humans, Membranes, Artificial, Models, Cardiovascular, Porosity, Tissue Engineering: methods
Abstract

The endometrium is the inner lining of the uterus. Following specific cyclic hormonal stimulation, endometrial stromal fibroblasts (stroma) and vascular endothelial cells exhibit morphological and biochemical changes to support embryo implantation and regulate vascular function, respectively. Herein, we integrated a resin-based porous membrane in a dual chamber microfluidic device in polydimethylsiloxane that allows long term in vitro co-culture of human endometrial stromal and endothelial cells. This transparent, 2-μm porous membrane separates the two chambers, allows for the diffusion of small molecules and enables high resolution bright field and fluorescent imaging. Within our primary human co-culture model of stromal and endothelial cells, we simulated the temporal hormone changes occurring during an idealized 28-day menstrual cycle. We observed the successful differentiation of stroma into functional decidual cells, determined by morphology as well as biochemically as measured by increased production of prolactin. By controlling the microfluidic properties of the device, we additionally found that shear stress forces promoted cytoskeleton alignment and tight junction formation in the endothelial layer. Finally, we demonstrated that the endometrial perivascular stroma model was sustainable for up to 4 weeks, remained sensitive to steroids and is suitable for quantitative biochemical analysis. Future utilization of this device will allow the direct evaluation of paracrine and endocrine crosstalk between these two cell types as well as studies of immunological events associated with normal vs. disease-related endometrial microenvironments.

Published
2017

5. Electromagnetic Property Characterization and Sensing of Endothelial Cells Growth Medium and Dulbecco's Phosphate Buffered Saline Solution for in vitro Cell Culture

Author

Viratikul, Rungrat, primary, Boonlom, Kamol, additional, Mancinelli, Elena, additional, Amsdon, Tim, additional, Chudpooti, Nonchanutt, additional, Hartley, Unalome Wetwatana, additional, Robertson, Ian, additional, Pensabene, Virginia, additional, Oberhammer, Joachim, additional, and Somjit, Nutapong, additional

Published
2022
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13. Leveraging bioengineering to assess cellular functions and communication within human fetal membranes.

Author

Eastman, Alison J., Noble, Kristen N., Pensabene, Virginia, and Aronoff, David M.

Abstract

The fetal membranes enclose the growing fetus and amniotic fluid. Preterm prelabor rupture of fetal membranes is a leading cause of preterm birth. Fetal membranes are composed of many different cell types, both structural and immune. These cells must coordinate functions for tensile strength and membrane integrity to contain the growing fetus and amniotic fluid. They must also balance immune responses to pathogens with maintaining maternal-fetal tolerance. Perturbation of this equilibrium can lead to preterm premature rupture of membranes without labor. In this review, we describe the formation of the fetal membranes to orient the reader, discuss some of the common forms of communication between the cell types of the fetal membranes, and delve into the methods used to tease apart this paracrine signaling within the membranes, including emerging technologies such as organ-on-chip models of membrane immunobiology. [ABSTRACT FROM AUTHOR]

Published
2022
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19. Polylactic is a Sustainable, Low Absorption, Low Autofluorescence Alternative to Other Plastics for Microfluidic and Organ-on-Chip Applications

Author

Ongaro, Alfredo E., primary, Di Giuseppe, Davide, additional, Kermanizadeh, Ali, additional, Miguelez Crespo, Allende, additional, Mencattini, Arianna, additional, Ghibelli, Lina, additional, Mancini, Vanessa, additional, Wlodarczyk, Krystian L., additional, Hand, Duncan P., additional, Martinelli, Eugenio, additional, Stone, Vicki, additional, Howarth, Nicola, additional, La Carrubba, Vincenzo, additional, Pensabene, Virginia, additional, and Kersaudy-Kerhoas, Maïwenn, additional

Published
2020
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24. Polylactic acid, a sustainable, biocompatible, transparent substrate material for Organ-On-Chip, and Microfluidic applications

Author

Ongaro, Alfredo E., primary, Giuseppe, Davide Di, additional, Kermanizadeh, Ali, additional, Crespo, Allende Miguelez, additional, Mencatti, Arianna, additional, Ghibelli, Lina, additional, Mancini, Vanessa, additional, Wlodarczyk, Krystian L., additional, Hand, Duncan P., additional, Martinelli, Eugenio, additional, Stone, Vicki, additional, Howarth, Nicola, additional, Carrubba, Vincenzo La, additional, Pensabene, Virginia, additional, and Kersaudy-Kerhoas, Maïwenn, additional

Published
2019
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29. Organs-on-Chips as Bridges for Predictive Toxicology

Author

Hutson, M. Shane, primary, Alexander, Peter G., additional, Allwardt, Vanessa, additional, Aronoff, David M., additional, Bruner-Tran, Kaylon L., additional, Cliffel, David E., additional, Davidson, Jeffrey M., additional, Gough, Albert, additional, Markov, Dmitry A., additional, McCawley, Lisa J., additional, McKenzie, Jennifer R., additional, McLean, John A., additional, Osteen, Kevin G., additional, Pensabene, Virginia, additional, Samson, Philip C., additional, Senutovitch, Nina K., additional, Sherrod, Stacy D., additional, Shotwell, Matthew S., additional, Taylor, D. Lansing, additional, Tetz, Lauren M., additional, Tuan, Rocky S., additional, Vernetti, Lawrence A., additional, and Wikswo, John P., additional

Published
2016
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31. Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor

Author

Brown, Jacquelyn A., primary, Pensabene, Virginia, additional, Markov, Dmitry A., additional, Allwardt, Vanessa, additional, Neely, M. Diana, additional, Shi, Mingjian, additional, Britt, Clayton M., additional, Hoilett, Orlando S., additional, Yang, Qing, additional, Brewer, Bryson M., additional, Samson, Philip C., additional, McCawley, Lisa J., additional, May, James M., additional, Webb, Donna J., additional, Li, Deyu, additional, Bowman, Aaron B., additional, Reiserer, Ronald S., additional, and Wikswo, John P., additional

Published
2015
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35. Instrumenting a Fetal Membrane on a Chip as Emerging Technology for Preterm Birth Research

Author

Gnecco, Juan S., Anders, Anjali P., Cliffel, David, Pensabene, Virginia, Rogers, Lisa M., Osteen, Kevin, and Aronoff, David M.

Abstract

Preterm birth (PTB) is clinically defined as process of giving birth before 37 weeks of gestation and is a leading cause of death among neonates and children under the age of five. Prematurity remains a critical issue in developed countries, yet our understanding of the pathophysiology of PTB remains largely unknown. Among pregnancy complications, subclinical infections such as chorioamnionitis (CAM) are implicated in up to 70% of PTB cases. Specifically, CAM is characterized by the infection of the fetal membranes that surround the developing fetus and extend from the placenta, and is often associated with preterm, premature rupture of the fetal membranes (PPROM). The fetal membrane plays a key structural role in maintaining the fetal and maternal compartments of the gravid uterus. However, our understanding of the mechanisms of PPROM and the spatio-temporal progress of CAM remains vastly unknown. A lack of human-derived models have hindered our understanding of the mechanism that govern spontaneous PTB. Thus, in this short review, we discuss the emerging microfabrication technologies, specifically, organ-on-chip (OoCs) models, that seek to recapitulate the cellular and molecular context of the gestational membranes in vitro. These models show promise to facilitate the investigation of pathologic mechanisms that drive these disease conditions by mimicking the interactive contribution of the major cell types that make up the microenvironment of the fetal membrane and enable high throughput screening. Herein, we histologically characterize the microenvironment of the fetal membrane as a metric for scaling to recapitulate the functional components of the human fetal membrane. We review the current OoC models of the gravid uterus and conceptualize an “Instrumented Fetal Membrane on a Chip” (IFMOC) design as a prototype for PPROM and CAM research. Lastly, we discuss further applications of these OoC models for toxicological or pharmacological screening and personalized medicine. Fetal membrane OoCs offer an innovative and valuable platform to explore complex interactions between multiple drug types, toxic substances, and/or pathogenic microbes and their potential impacts on pregnancy outcomes. Further work will be required by integrating technological and analytical capabilities in order to characterize the fetal membrane microenvironment for preterm birth research.

Published
2017
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36. Neurovascular unit on a chip: implications for translational applications

Author

Alcendor, Donald J, primary, Block III, Frank E, additional, Cliffel, David E, additional, Daniels, John Scott, additional, Ellacott, Kate LJ, additional, Goodwin, Cody R, additional, Hofmeister, Lucas H, additional, Li, Deyu, additional, Markov, Dmitry A, additional, May, Jody C, additional, McCawley, Lisa J, additional, McLaughlin, BethAnn, additional, McLean, John A, additional, Niswender, Kevin D, additional, Pensabene, Virginia, additional, Seale, Kevin T, additional, Sherrod, Stacy D, additional, Sung, Hak-Joon, additional, Tabb, David L, additional, Webb, Donna J, additional, and Wikswo, John P, additional

Published
2013
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48. A pilot study on a new anchoring mechanism for surgical applications based on mucoadhesives.

Author

Tognarelli, Selene, Pensabene, Virginia, Condino, Sara, Valdastri, Pietro, Menciassi, Arianna, Arezzo, Alberto, and Dario, Paolo

Subjects
*BIOPHYSICS, *ENDOSCOPIC surgery, *LAPAROSCOPY, *RESEARCH methodology, *RESEARCH funding, *TISSUES, *PILOT projects
Abstract

In order to minimize the invasiveness of laparoscopic surgery, different techniques are emerging from research to clinical practice. Whether the incision is performed on the outside - as in Single Port Laparoscopy (SPL) - or on the inside - as in Natural Orifice Transluminal Endoscopic Surgery (NOTES) - of the patient's body, inserting and operating all the instruments from a single access site seems to be the next challenge in surgery. Magnetic guidance has been recently proposed for controlling surgical tools deployed from a single access. However, the exponential drop of magnetic field with distance makes this solution suitable only for the upper side of the abdominal cavity in nonobese patients. In the present paper we introduce a polymeric anchoring mechanism to lock surgical assistive tools inside the gastric cavity, based on the use of mucoadhesive films. Mucoadhesive properties of four formulations, with different chemical components and concentration, are evaluated by using both in vitro and ex vivo test benches on porcine stomach samples. Hydration of mucoadhesive films by contact with the aqueous mucous layer is analyzed by means of in vitro swelling tests, whereas optimal preloading conditions and adhesion performances, in terms of detachment force, supported weight and size are investigated ex vivo. Mucoadhesion is observed with all the four formulations. For a contact area of 113 mm2, the maximum normal and shear detachment forces withstood by the adhesive film are 2,6 N and 1 N respectively. These values grow up to 12,14 N and 4,5 N when the contact area increases to 706 mm2. Lifetime of the bonding on the inner side of the stomach wall was around two hours. Mucoadhesive anchoring represents a fully biocompatible and safe approach to deploy multiple assistive surgical tools on mucosal tissues by minimizing the number of access ports. This technique has been quantitatively assessed ex vivo for anchoring on the inner wall of the gastric cavity or in gastroscopic surgery. By properly varying the chemical formulation, this approach can be extended to other cavities of the human body. [ABSTRACT FROM AUTHOR]

Published
2011
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49. Dispersion of Multi-walled Carbon Nanotubes in Aqueous Pluronic F127 Solutions for Biological Applications.

Author

Ciofani, Gianni, Raffa, Vittoria, Pensabene, Virginia, Menciassi, Arianna, and Dario, Paolo

Subjects
CARBON nanotubes, NANOTUBES, SURFACE active agents, FULLERENES, SUSPENSIONS (Chemistry), SURFACE chemistry
Abstract

Because mass-produced carbon nanotubes (CNTs) are strongly aggregated and highly hydrophobic, processes to make them water soluble are required for biological applications. Suspensions in surfactant solutions are often employed. Among these, Pluronic F127 appear to be highly biocompatible if used at low concentrations. Starting from these results, this work involves a systematic study to clarify the dispersion behaviour of CNTs in Pluronic F127. The results suggest a two-step process: first, the bundles disaggregate, kinetically driven by the energy supplied to the system; second, they disperse (surfactant adsorption), thermodynamically driven by the surfactant concentration. The dispersion reaction data are well fitted by a first-order kinetics reaction. By performing a pretreatment step, consisting of stirring at 70°C, the achieved concentration of CNTs in solution is twice that of the traditional process. The proposed procedure provides an optimal compromise between a low Pluronic concentration and a high CNT concentration. [ABSTRACT FROM AUTHOR]

Published
2009
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