scholarly journals Breaking the Third Wall: Implementing 3D-Printing Technics to Expand the Complexity and Abilities of Multi-Organ-on-a-Chip Devices

Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 627
Author(s):  
Yoel Goldstein ◽  
Sarah Spitz ◽  
Keren Turjeman ◽  
Florian Selinger ◽  
Yechezkel Barenholz ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cfd Simulation ◽  
Cost Effective ◽  
In Vitro Models ◽  
3D Print ◽  
Biological Compatibility ◽  
3D Printed ◽  
Organ On A Chip

The understanding that systemic context and tissue crosstalk are essential keys for bridging the gap between in vitro models and in vivo conditions led to a growing effort in the last decade to develop advanced multi-organ-on-a-chip devices. However, many of the proposed devices have failed to implement the means to allow for conditions tailored to each organ individually, a crucial aspect in cell functionality. Here, we present two 3D-print-based fabrication methods for a generic multi-organ-on-a-chip device: One with a PDMS microfluidic core unit and one based on 3D-printed units. The device was designed for culturing different tissues in separate compartments by integrating individual pairs of inlets and outlets, thus enabling tissue-specific perfusion rates that facilitate the generation of individual tissue-adapted perfusion profiles. The device allowed tissue crosstalk using microchannel configuration and permeable membranes used as barriers between individual cell culture compartments. Computational fluid dynamics (CFD) simulation confirmed the capability to generate significant differences in shear stress between the two individual culture compartments, each with a selective shear force. In addition, we provide preliminary findings that indicate the feasibility for biological compatibility for cell culture and long-term incubation in 3D-printed wells. Finally, we offer a cost-effective, accessible protocol enabling the design and fabrication of advanced multi-organ-on-a-chip devices.

scholarly journals Tailoring 3D cell culture templates with common hydrogels

2018 ◽  
Author(s):  
Aurélien Pasturel ◽  
Pierre-Olivier Strale ◽  
Vincent Studer
Keyword(s):  
Cell Culture ◽  
3D Cell Culture ◽  
In Vitro Models ◽  
Manufacturing Method ◽  
Biologically Relevant ◽  
Physiological Conditions ◽  
Subtractive Manufacturing ◽  
User Friendly

3D cell culture aims at reconciliating the simplicity of in vitro models with the human like properties encountered in vivo. Soft permeable hydrogels have emerged as user-friendly materials to grow cells in more physiological conditions. With the intent on turning these homogeneous substrates into biomimetic templates, we introduce a generic solution compatible with the most biologically relevant and often frail materials. Here we take control of the chemical environment driving generic radical reactions to craft common gels with patterned light. In a simple microreactor, we harness the well-known inhibition of radicals by oxygen to enable topographical photopolymerization. Strikingly, by sustaining an oxygen rich environment, we can also induce hydrogel photo-scission which turns out to be a powerful and generic subtractive manufacturing method. We finally introduce a flexible patterned functionalization protocol based on available photo-linkers. Using these common tools on the most popular hydrogels, we tailored soft templates where cells grow or self-organize into standardized structures. The platform we describe has the potential to set a standard in future 3D cell culture experiments.

scholarly journals Cortical Spheroid Model for Studying the Effects of Ischemic Brain Injury

2021 ◽  
Author(s):  
Rachel M McLaughlin ◽  
Amanda Laguna ◽  
Ilayda Top ◽  
Christien Hernadez ◽  
Liane L Livi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Cost Effective ◽  
Glucose Deprivation ◽  
In Vitro Models ◽  
3D Architecture ◽  
A Cell ◽  
Antioxidant Agent

Stroke is a devastating neurological disorder and a leading cause of death and long-term disability. Despite many decades of research, there are still very few therapeutic options for patients suffering from stroke or its consequences. This is partially due to the limitations of current research models, including traditional in vitro models which lack the three-dimensional (3D) architecture and cellular make-up of the in vivo brain. 3D spheroids derived from primary postnatal rat cortex provide an in vivo-relevant model containing a similar cellular composition to the native cortex and a cell-synthesized extracellular matrix. These spheroids are cost-effective, highly reproducible, and can be produced in a high-throughput manner, making this model an ideal candidate for screening potential therapeutics. To study the cellular and molecular mechanisms of stroke in this model, spheroids were deprived of glucose, oxygen, or both oxygen and glucose for 24 hours. Both oxygen and oxygen-glucose deprived spheroids demonstrated many of the hallmarks of stroke, including a decrease in metabolism, an increase in neural dysfunction, and an increase in reactive astrocytes. Pretreatment of spheroids with the antioxidant agent N-acetylcysteine (NAC) mitigated the decrease in ATP seen after 24 hours of oxygen-glucose deprivation. Together, these results show the utility of our 3D cortical spheroid model for studying ischemic injury and its potential for screening stroke therapeutics.

scholarly journals 2153

2017 ◽  
Vol 1 (S1) ◽  
pp. 2-2
Author(s):  
Rahima Benhabbour ◽  
Rima Janusziewicz ◽  
Sue J. Mecham ◽  
Roopali Shrivastava ◽  
Gayane Paravyan
Keyword(s):  
Release Kinetics ◽  
Cost Effective ◽  
Unintended Pregnancies ◽  
Hiv Positive Mothers ◽  
Study Population ◽  
3D Printed ◽  
Injection Molded ◽  
In Vivo Characterization

OBJECTIVES/SPECIFIC AIMS: The long-term goal of this project is to develop a cost effective 3D printed multipurpose intravaginal ring (IVR) to prevent against unintended pregnancies and infectious diseases.Our goal is to develop a female-controlled method for prevention using innovative IVRs. METHODS/STUDY POPULATION: In vitro and in vivo characterization. RESULTS/ANTICIPATED RESULTS: Controlled and fine-tuned release kinetics 100% drug release from 3D printed IVRs compared with 10%–15% with traditional injection molded IVRs cost-effective engineering of multipurpose IVR with CLIP 3D printing technology. DISCUSSION/SIGNIFICANCE OF IMPACT: If successful, this project will revolutionize the engineering of IVRs and will have a global impact on human health. Not only we will help save millions of women around the world but also millions of children that are infected by their HIV-positive mothers through gestation or breast feeding.

scholarly journals A Simple Aspect Ratio Dependent Method of Patterning Microwells for Selective Cell Attachment

2018 ◽  
Author(s):  
Erik A. Zavrel ◽  
Michael L. Shuler ◽  
Xiling Shen
Keyword(s):  
Cell Culture ◽  
Cell Attachment ◽  
In Vitro Models ◽  
Contact Printing ◽  
Deep Well ◽  
Biomimetic Approach ◽  
Authentic Environment ◽  
And Control

3-D culture has been shown to provide cells with a more physiologically authentic environment than traditional 2-D (planar) culture [1, 2]. 3-D cues allow cells to exhibit more realistic functions and behaviors, e.g., adhesion, spreading, migration, metabolic activity, and differentiation. Knowledge of changes in cell morphology, mechanics, and mobility in response to geometrical cues and topological stimuli is important for understanding normal and pathological cell development [3]. Microfabrication provides unique in vitro approaches to recapitulating in vivo conditions due to the ability to precisely control the cellular microenvironment [4, 5]. Microwell arrays have emerged as robust alternatives to traditional 2D cell culture substrates as they are relatively simple and compatible with existing laboratory techniques and instrumentation [6, 7]. In particular, microwells have been adopted as a biomimetic approach to modeling the unique micro-architecture of the epithelial lining of the gastrointestinal (GI) tract [8–10]. The inner (lumen-facing) surface of the intestine has a convoluted topography consisting of finger-like projections (villi) with deep well-like invaginations (crypts) between them. The dimensions of villi and crypts are on the order of hundreds of microns (100–700 μm in height and 50–250 μm in diameter) [11]. While microwells have proven important in the development of physiologically realistic in vitro models of human intestine, existing methods of ensuring their surface is suitable for cell culture are lacking. Sometimes it is desirable to selectively seed cells within microwells and confine or restrict them to the microwells in which they are seeded. Existing methods of patterning microwells for cell attachment either lack selectivity, meaning cells can adhere and migrate anywhere on the microwell array, i.e., inside microwells or outside of them, or necessitate sophisticated techniques such as micro-contact printing, which requires precise alignment and control to selectively pattern the bottoms of microwells for cell attachment [12, 13].

scholarly journals Janus 3D printed dynamic scaffolds for nanodeflection-driven bone regeneration

2020 ◽  
Author(s):  
Sandra Camarero-Espinosa ◽  
Lorenzo Moroni
Keyword(s):  
Phase Segregation ◽  
In Vitro Models ◽  
Ultrasound Transducers ◽  
Cellular Functions ◽  
External Application ◽  
Matrix Deposition ◽  
Physical Stimuli ◽  
3D Printed

Abstract The application of physical stimuli to cell cultures has shown potential to modulate multiple cellular functions including migration, differentiation and survival. However, the relevance of these in-vitro models to future potential extrapolation in-vivo depends on whether stimuli can be applied “externally”, without invasive procedures. Here, we report on the fabrication and exploitation of dynamic additive-manufactured Janus scaffolds that are activated “on-command” via external application of ultrasounds, resulting in a mechanical nanodeflection that is transmitted to the surrounding cells. Janus scaffolds were spontaneously formed via phase-segregation of biodegradable polycapolactone (PCL) and polylactide (PLA) blends during the manufacturing process and behave as ultrasound transducers (acoustic to mechanical) where the PLA and PCL phases represent the active and backing materials, respectively. Remote stimulation of Janus scaffolds led to enhanced cell proliferation, matrix deposition and osteogenic differentiation of seeded bone marrow derived stromal cells (BMSCs) via formation and activation of voltage-gated calcium ion channels.

scholarly journals Review of Design Considerations for Brain-on-a-Chip Models

Micromachines ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 441
Author(s):  
Tiffany Cameron ◽  
Tanya Bennet ◽  
Elyn Rowe ◽  
Mehwish Anwer ◽  
Cheryl Wellington ◽  
...  
Keyword(s):  
Brain Research ◽  
Neurovascular Unit ◽  
Cell Monolayer ◽  
Cell Types ◽  
In Vitro Models ◽  
Research Field ◽  
Design Development ◽  
Organ On A Chip

In recent years, the need for sophisticated human in vitro models for integrative biology has motivated the development of organ-on-a-chip platforms. Organ-on-a-chip devices are engineered to mimic the mechanical, biochemical and physiological properties of human organs; however, there are many important considerations when selecting or designing an appropriate device for investigating a specific scientific question. Building microfluidic Brain-on-a-Chip (BoC) models from the ground-up will allow for research questions to be answered more thoroughly in the brain research field, but the design of these devices requires several choices to be made throughout the design development phase. These considerations include the cell types, extracellular matrix (ECM) material(s), and perfusion/flow considerations. Choices made early in the design cycle will dictate the limitations of the device and influence the end-point results such as the permeability of the endothelial cell monolayer, and the expression of cell type-specific markers. To better understand why the engineering aspects of a microfluidic BoC need to be influenced by the desired biological environment, recent progress in microfluidic BoC technology is compared. This review focuses on perfusable blood–brain barrier (BBB) and neurovascular unit (NVU) models with discussions about the chip architecture, the ECM used, and how they relate to the in vivo human brain. With increased knowledge on how to make informed choices when selecting or designing BoC models, the scientific community will benefit from shorter development phases and platforms curated for their application.

scholarly journals Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 737 ◽  
Author(s):  
Fahriye Duzagac ◽  
Gloria Saorin ◽  
Lorenzo Memeo ◽  
Vincenzo Canzonieri ◽  
Flavio Rizzolio
Keyword(s):  
Ex Vivo ◽  
Fluid Flows ◽  
Cost Effective ◽  
In Vitro Models ◽  
Organoid Culture ◽  
Self Organized ◽  
Quantum Leap ◽  
High Degree

Organ-like cell clusters, so-called organoids, which exhibit self-organized and similar organ functionality as the tissue of origin, have provided a whole new level of bioinspiration for ex vivo systems. Microfluidic organoid or organs-on-a-chip platforms are a new group of micro-engineered promising models that recapitulate 3D tissue structure and physiology and combines several advantages of current in vivo and in vitro models. Microfluidics technology is used in numerous applications since it allows us to control and manipulate fluid flows with a high degree of accuracy. This system is an emerging tool for understanding disease development and progression, especially for personalized therapeutic strategies for cancer treatment, which provide well-grounded, cost-effective, powerful, fast, and reproducible results. In this review, we highlight how the organoid-on-a-chip models have improved the potential of efficiency and reproducibility of organoid cultures. More widely, we discuss current challenges and development on organoid culture systems together with microfluidic approaches and their limitations. Finally, we describe the recent progress and potential utilization in the organs-on-a-chip practice.

scholarly journals Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip

Micromachines ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 599 ◽  
Author(s):  
Neda Azizipour ◽  
Rahi Avazpour ◽  
Derek H. Rosenzweig ◽  
Mohamad Sawan ◽  
Abdellah Ajji
Keyword(s):  
Disease Modeling ◽  
Biomedical Application ◽  
Lab On A Chip ◽  
In Vitro Models ◽  
Future Perspectives ◽  
Versatile Tool ◽  
Organ On A Chip ◽  
Review Current

Following the advancements in microfluidics and lab-on-a-chip (LOC) technologies, a novel biomedical application for microfluidic based devices has emerged in recent years and microengineered cell culture platforms have been created. These micro-devices, known as organ-on-a-chip (OOC) platforms mimic the in vivo like microenvironment of living organs and offer more physiologically relevant in vitro models of human organs. Consequently, the concept of OOC has gained great attention from researchers in the field worldwide to offer powerful tools for biomedical researches including disease modeling, drug development, etc. This review highlights the background of biochip development. Herein, we focus on applications of LOC devices as a versatile tool for POC applications. We also review current progress in OOC platforms towards body-on-a-chip, and we provide concluding remarks and future perspectives for OOC platforms for POC applications.

scholarly journals Engineering Microfluidic Organoid-on-a-Chip Platforms

Micromachines ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 165 ◽  
Author(s):  
Fang Yu ◽  
Walter Hunziker ◽  
Deepak Choudhury
Keyword(s):  
Cost Effective ◽  
In Vitro Models ◽  
Multipotent Stem Cells ◽  
Self Organized ◽  
Complex Organization ◽  
Culture Models ◽  
And Function ◽  
Cell Culture Models

In vitro cell culture models are emerging as promising tools to understand human development, disease progression, and provide reliable, rapid and cost-effective results for drug discovery and screening. In recent years, an increasing number of in vitro models with complex organization and controlled microenvironment have been developed to mimic the in vivo organ structure and function. The invention of organoids, self-organized organ-like cell aggregates that originate from multipotent stem cells, has allowed a whole new level of biomimicry to be achieved. Microfluidic organoid-on-a-chip platforms can facilitate better nutrient and gas exchange and recapitulate 3D tissue architecture and physiology. They have the potential to transform the landscape of drug development and testing. In this review, we discuss the challenges in the current organoid models and describe the recent progress in the field of organoid-on-a-chip.

scholarly journals Pre-Clinical In Vitro Models Used in Cancer Research: Results of a Worldwide Survey

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6033
Author(s):  
Sarai Martinez-Pacheco ◽  
Lorraine O’Driscoll
Keyword(s):  
Cancer Research ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Cost Effective ◽  
Cell Types ◽  
3D Models ◽  
In Vitro Models ◽  
3D Cultures

To develop and subsequently get cancer researchers to use organotypic three-dimensional (3D) models that can recapitulate the complexity of human in vivo tumors in an in vitro setting, it is important to establish what in vitro model(s) researchers are currently using and the reasons why. Thus, we developed a survey on this topic, obtained ethics approval, and circulated it throughout the world. The survey was completed by 101 researchers, across all career stages, in academia, clinical or industry settings. It included 40 questions, many with multiple options. Respondents reported on their field of cancer research; type of cancers studied; use of two-dimensional (2D)/monolayer, 2.5D and/or 3D cultures; if using co-cultures, the cell types(s) they co-culture; if using 3D cultures, whether these involve culturing the cells in a particular way to generate spheroids, or if they use additional supports/scaffolds; techniques used to analyze the 2D/2.5D/3D; and their downstream applications. Most researchers (>66%) only use 2D cultures, mainly due to lack of experience and costs. Despite most cancer researchers currently not using the 3D format, >80% recognize their importance and would like to progress to using 3D models. This suggests an urgent need to standardize reliable, robust, reproducible methods for establishing cost-effective 3D cell culture models and their subsequent characterization.

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