Womb-on-a-chip biomimetic system for improved embryo culture and development

Chang, Kuo Wei; Chang, Pei Yu; Huang, Hsiao‐Ping; Li, Chin Jung; Tien, Chang Hung; Yao, Da; Fan, Shih-Kang; Hsu, Wensyang; Liu, Cheng-Hsien

doi:10.1016/j.snb.2015.11.004

Cited by 24 publications

(17 citation statements)

References 40 publications

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“…This model enhanced the quality of embryo culture by utilizing microfluidic technologies. A more recent, but similar approach was taken by Chang et al to develop a comprehensive stand-alone microfluidic platform, "Womb-on-a Chip", that mimics the microenvironment and incorporates key parameters of embryo implantation, including mild biomechanical forces (29). This model used PDMS based microfluidic chambers to directly co-culture primary endometrial stromal fibroblasts with murine embryos with the ability to visualize the implantation process in real time.…”

Section: Ooc Models Of Embryo Implantationmentioning

confidence: 99%

Instrumenting a Fetal Membrane on a Chip as Emerging Technology for Preterm Birth Research

Gnecco

Anders

Cliffel

et al. 2018

CPD

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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.

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Section: Ooc Models Of Embryo Implantationmentioning

confidence: 99%

Instrumenting a Fetal Membrane on a Chip as Emerging Technology for Preterm Birth Research

Gnecco

Anders

Cliffel

et al. 2018

CPD

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“…Microfluidic chips have been used to study the developments of embryos and the growth of cells (e.g., [35,36,37]). Based on the above experiences and by incorporating the concepts of Lego, we developed an approach of building versatile microfluidic chips to study the developments of fish embryos (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

Workshop, Cost-Effective and Streamlined Fabrications of Re-Usable World-To-Chip Connectors for Handling Sample of Limited Volume and for Assembling Chip Array

Lue

Kuo

2018

Sensors

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The world-to-chip interface is an essential yet intriguing part of making and employing microfluidic devices. A user-friendly connector could be expensive or difficult to make. We fabricated two ports of microfluidic chips with easily available materials including Teflon blocks, double adhesive films, coverslips, and transparency films. By using a mini grinder, coverslips were drilled to form small holes for the fluid passages between port and chip. Except for the double adhesive films, the resultant ports are durable and re-useable. The DK1 port, contains a mini three-way switch which allows users to handle fluid by a tube-connected pump, or by a manual pipette for the sample of trace amount. The other port, the DK2 port, provides secured tube-connections. Importantly, we invented a bridge made of craft cutter-treated transparency films and double adhesive films to mediate liquid flow between DK2 port and chip. With the use of a bridge, users do not need to design new ports for new chips. Also, individual chips could be linked by a bridge to form a chip array. We successfully applied DK1 port on a microfluidic chip where green fluorescent protein was immobilized. We used DK2 port on an array of fish chips where the embryos of zebra fish developed.

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“…The reproduction of a total uterine system on a microfluidic chip might be of great impact for in vitro fertilization-embryo transplantation (IVF-ET) (43) and for testing the efficacy and toxicity of new drugs (42). After various attempts to mimic the physiological function of the reproductive system (43,44) recently an advanced and extremely attractive and promising system has been realized by Xiao et al (42), the so called EVATAR ("avatar", digital representation of an individual, plus the name "Eve"). This powerful tool phenocopies the human menstrual cycle and pregnancy by reproducing the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues.…”

Section: Uterus-on-a-chipmentioning

confidence: 99%