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SELECTBIO Conferences Organ-on-a-Chip and Body-on-a-Chip: In Vitro Systems Mimicking In Vivo Functions "Track A"

Organ-on-a-Chip and Body-on-a-Chip: In Vitro Systems Mimicking In Vivo Functions "Track A" Agenda

Co-Located Conference Agendas

3D-Culture & Organoids | Stem Cells in Drug Discovery & Toxicity Screening 2018 | 

Other Track Agendas

3D-Bioprinting "Track B" | Organ-on-a-Chip and Body-on-a-Chip: In Vitro Systems Mimicking In Vivo Functions "Track A" | 

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Thursday, 4 October 2018


Conference Registration, Materials Pick-Up, Morning Coffee, and Breakfast Pastries

Session Title: Conference Opening Plenary Session

Plenary Session Chair: Linda Griffith, Ph.D., Professor, Massachusetts Institute of Technology (MIT)


Roger KammKeynote Presentation

Microphysiological Models for Metastatic Cancer
Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, Massachusetts Institute of Technology (MIT), United States of America

Circulating tumor cells form metastases by reaching a distant microcirculation, undergoing transendothelial migration, entering the remote tissue and proliferating.  Microfluidic assays have been developed to visualize and quantify this process within vascular networks that recapitulate aspects of the in vivo microcirculation.  Tumor cells, with or without accompanying immune cells, are streamed into a vascular network grown in a 3D matrix, some fraction of which arrest and extravasate into the surrounding matrix. These studies provide detailed information on the ability of different tumor cell types to extravasate, the adhesion molecules they use, and the effects of various other cell types in the intravascular and extravascular spaces.  While these models are largely organ-independent, work has also begun to investigate the specificity of certain cancers to metastasize to organs such as the brain.  For this purpose, a model of the blood-brain barrier has been produced, characterized in terms of its morphology and vascular permeability, and then used it to explore extravasation and tumor formation with the brain as the target organ.


Nancy AllbrittonKeynote Presentation

Intestine on a Chip for Basic Biology and Patient-Specific Medicine
Nancy Allbritton, Kenan Professor of Chemistry and Biomedical Engineering and Chair of the Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, United States of America

Technical advances are making it possible to create tissue microenvironments on platforms that are compatible with high-content screening strategies. We have developed microfabricated devices to enable culture of organized cellular structures which possess much of the complexity and function of intact intestinal tissue.  Stem-cell culture enables single stem cells or intestinal crypts isolated from primary small or large intestine from humans or mice to grow and persist indefinitely as organotypic structures containing all of the expected lineages of the intestinal epithelium.  Our microengineered arrays and fluidic devices build on this knowledge base to reconstruct millimeter-scale primary intestinal epithelium that closely mimics the polarized 3D in vivo microarchitecture of the intestine Chemical gradients of growth and differentiation factors as well as cytokines are readily applied across the tissues. These bioanalytical platforms are envisioned as next generation systems for assay of microbiome-, drug- and toxin-interactions with the intestinal epithelia. Finally intestinal biopsy samples can be used to populate the constructs with cells producing patient-specific tissues for personalized medicine.


Shoji TakeuchiKeynote Presentation

Cell Fiber Technology For 3D Tissue-on-a-Chip Application
Shoji Takeuchi, Professor, Center For International Research on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, Japan

The talk describes a 3D cell culture method using core-shell hydrogel microfibers (cell fibers). The core is filled with cells and ECM proteins, and the shell is composed of calcium alginate. Since the core diameter is about 100 microns, oxygen and nutrients can be diffused into the central area of the 3D tissue; therefore this culture system allows us to culture the tissue for a long period without central necrosis. Using this culture system, fiber-based tissues such as blood vessels, nerves, and muscles can be formed with in the core. Here, I will discuss the application of the cell fiber technology for various tissue-on-a-chip studies including cardiac tissue, neuro-muscular junctions, and vascularized skin etc.


Paul GatenholmKeynote Presentation

3D Bioprinting of Soft Tissue: Translation to Clinic
Paul Gatenholm, Professor, Director of 3D Bioprinting Center, Chalmers University of Technology, Sweden; CEO, CELLHEAL AS, Norway, Sweden

3D Bioprinting has a potential to revolutionize regenerative medicine due to unique ability to place multiple cell types in predetermined position and build bottom up the microenvironment to control cellular fate processes. Adult stem cells can be harvested in operating room and combined with biopolymeric hydrogels and 3D bioprinted into desire shape. We have focused our research onto translation of 3D bioprinting technology to clinic. Together with plastic surgeons we are studying preclinical transplantation of 3D bioprinted constructs with stem cells isolated from patient in operating room. The goal is to promote wound healing and repair soft tissue. Translation includes regulatory approved cell isolation protocols and use of regulatory compliant bioinks. We have invented cell-instructive bioinks to be able to control cellular fate processes and to grow vascularized tissue which is of great interest for bringing 3D Bioprinting technology to clinic and space applications.


Coffee Break and Networking in the Exhibit Hall


Reyk HorlandKeynote Presentation

Industrial Adoption of Integrated Multi-Organ-Chip Solutions
Reyk Horland, CEO, TissUse GmbH, Germany

Microphysiological systems have proven to be a powerful tool for recreating human tissue- and organ-like functions at research level. This provides the basis for the establishment of qualified preclinical assays with improved predictive power. Industrial adoption of microphysiological systems and respective assays is progressing slowly due to their complexity. In the first part of the presentation examples of industrial transfer of single-organ chip and two-organ chip solutions are highlighted. The underlying universal microfluidic Multi-Organ-Chip (MOC) platform of a size of a microscopic slide integrating an on-chip micro-pump and capable to interconnect different organ equivalents will be presented. The second part of the presentation focusses on the challenges to translate a MOC-based combination of four human organ equivalents into a commercially useful tool for ADME profiling and toxicity testing of drug candidates. This four-organ tissue chip combines intestine, liver and kidney equivalents for adsorption, metabolism and excretion respectively. Furthermore, it provides an additional tissue culture compartment for a fourth organ equivalent, e.g. skin or neuronal tissue for extended toxicity testing. Issues to ensure long-term performance and industrial acceptance of such complex microphysiological systems, such as design criteria, tissue supply and on chip tissue homeostasis will be discussed.


Norio NakatsujiKeynote Presentation

Human Pluripotent Stem Cell-derived Cardiomyocytes/Neurons on 3D Micro-Tissue Devices for Matured and Functional Cell Products in Drug Discovery and Screening
Norio Nakatsuji, Chief Advisor, Stem Cell & Device Laboratory, Inc. (SCAD); Professor Emeritus, Kyoto University, Japan

Human pluripotent stem (PS) cells, including ES and iPS cells, are promising sources of various model cells for drug discovery and toxicology screening.  However, there are important (but still unsatisfactory) needs of more matured and functional cells with reliable and low-cost production from human iPS or ES cells. We developed a method of robust and low-cost cytokine-free differentiation of cardiomyocytes from human ES/iPS cells by combination of small chemical compounds.  We also developed low-cost and labor-saving methods for construction of 3D multi-cellular devices with aligned nanofibers for more matured and functional cell device products. Our human iPSC-derived cardiomyocytes or neurons seeded on nanofiber scaffolds form 3D multi-layered structures (Micro-Tissues), which show matured and stable cell/tissue functions. Our Micro-Tissue devices are easy to handle and useful for drug screening and toxicology assays.


Linda GriffithKeynote Presentation

Multi-MPS Interactions for Chronic Inflammatory Disease: A Scaling Challenge
Linda Griffith, Professor, Massachusetts Institute of Technology (MIT), United States of America

The pioneering work of Shuler and colleagues over 20 year ago demonstrated the potential for using interconnected MPS for pharmacology and toxicology applications by showing metabolic conversion of a compound in one MPS and downstream effects on a second MPS.  As the role of immunological contributions to drug safety have become more appreciated, the need for more complex immunologically-competent MPS has grown.  This has driven development of more complex MPS that are also potentially valuable for modeling inflammatory diseases. This talk will address technical challenges in modeling complex diseases with  “organs on chips” approaches include the need for relatively large tissue masses and organ-organ cross talk to capture systemic effects, as well as new ways of thinking about scaling to capture multiple different functionalities from drug clearance to cytokine signaling crosstalk. An example of how gut-liver interactions can be parsed at these levels will be featured, along with new approaches for culturing complex 3D tissues with synthetic extracellular matrix and higher-order multi-organ interactions involving immunology.


Networking Lunch in the Exhibit Hall -- Meet the Exhibitors and View Posters

Session Title: Emerging Technologies and Approaches in Organs-on-Chips Field


Michael ShulerKeynote Presentation

Human “Body-on-a-Chip” Systems to Test Drug Efficacy and Toxicity
Michael Shuler, Samuel B. Eckert Professor of Engineering, Cornell University, President Hesperos, Inc., United States of America

Human microphysiological or “Body-on-a-Chip” systems are potentially powerful tools to assess both the potential efficacy and toxicity of drugs in pre-clinical studies.  Having a human based, multiorgan system, that emulates key aspects of human physiology can provide important insights to complement animal studies in the decision about which drugs to move into clinical trials.  Our human surrogates are constructed using a low cost, robust “pumpless” platform.  We use this platform in conjunction with “functional” measurements of electrical and mechanical activity of tissue constructs (in collaboration with J. Hickman, University of Central Florida). Using a system with four or more organs we can predict the exchange of metabolites between organ compartments in response to various drugs, combintions of drugs and various dose levels.  We will provide examples of using the system to both predict the response of a target tissue as well as off-target responses in other tissues/organs.  We believe such models will allow improved predictions of human clinical response from preclinical studies.


Organs-on-Chips Technology Enables Better Understanding of Human Pathogenesis and Development of Therapeutics
Janna Nawroth, Principal Investigator, R&D Lead, Emulate, Inc., United States of America

Organs-on-Chips are micro-engineered systems that recapitulate the tissue microenvironment. Each Organ-Chip, which is composed of a clear flexible polymer, is about the size of an AA battery and contains tiny hollow channels lined with living cells. The Chips are cultured under continuous flow within engineered 3D microenvironments that go beyond conventional 3D in vitro models by recapitulating in vivo intercellular interactions, spatiotemporal gradients, vascular perfusion, and mechanical forces — all key drivers of cell architecture, differentiated function, and gene expression. In this presentation, we discuss data from studies conducted with academic and industry collaborators that demonstrates the utility of the system as a more predictive, human-relevant alternative for preclinical disease modeling and drug discovery.  In one case, we investigated the potential for our Small Airway-Chip to demonstrate asthma exacerbation in response to viral infection. First, we induced key pathophysiological hallmarks of the asthmatic epithelium by exposing the epithelial side to clinically relevant doses of IL-13. Then, we administered a rhinoviral infection and recapulated complex clinical features of viral-induced asthma exacerbation in real time. For example, we observed increased ciliated cell sloughing, altered ciliary beating frequency, goblet cells hyperplasia, increased expression of adhesion molecules in microvascular endothelial cells and inflammatory mediator release that have been observed in asthmatics and individuals infected with rhinovirus. A novel, high resolution temporal analysis of secreted inflammatory markers revealed alteration of IL-6, IFN-?1 and CXCL10 secretory phases after rhinovirus infection in the IL-13 enriched environment. Furthermore, using real time high resolution imaging and quantitative analysis of circulating inflammatory cells, we also demonstrated the efficacy of a CXCR2 antagonist to reduce adhesion, motility and transmigration of perfused human neutrophils. These studies demonstrate how our Organs-on-Chips technology provides a platform to obtain powerful preclinical data for understanding the mechanisms that underlie disease pathologensis and enable development of new therapeutics.


Veryst Engineering, LLCModeling and Simulation of Microfluidic Organ-on-a-Chip Devices
Matthew Hancock, Managing Engineer, Veryst Engineering, LLC

Modeling and simulation are key components of the engineering development process, providing a rational, systematic method to engineer and optimize products and dramatically accelerate the development cycle over a pure intuition-driven, empirical testing approach. Modeling and simulation help to identify key parameters related to product performance (“what to try”) as well as insignificant parameters or conditions related to poor outcomes (“what not to try”). For microfluidic organ-on-chip devices, modeling and simulation can inform the design and integration of common components such as mixers, micropumps, manifolds, and channel networks. Modeling and simulation may also be used to estimate a range of processes occurring within the fluid bulk and near cells, including shear stresses, transport of nutrients and waste, chemical reactions, heat transfer, and surface tension & wetting effects. I will discuss how an array of modeling tools such as scaling arguments, analytical formulas, and finite element simulations may be leveraged to address these microfluidic organ-on-a-chip device development issues. I will also work through a few examples in detail.


Afternoon Coffee Break and Networking in the Exhibit Hall


Microfluidic ChipShop GmbHChallenges and Solutions for Industrial Manufacturing of Organ-on-a-Chip Devices
Holger Becker, Chief Scientific Officer, Microfluidic ChipShop GmbH

While organ-on-a-chip is an academically thriving field in recent years, the successful commercialization of such devices will depend on the ability for industrial manufacturing. The presentation will highlight a variety of organ-on-a-chip devices which have been developed with methods paving the way towards commercial use and the associated challenges for volume manufacturing.


CorSolutionsEssential Tools for Ensuring Successful Outcomes in 3D Cell Culture and Other Microfluidic Experiments
Thomas Corso, Chief Technical Officer, CorSolutions

The subtleties that arise in microfluidic experiments are frequently overlooked which can negatively impact the robustness, reproducibility and reliability of the outcome.  However if the microfluidic researcher has the correct tools in their toolbox, these subtleties and nuances can be understood and often circumvented.  These essential tools for troubleshooting problematic microfluidic experiments will be discussed including flow meters and pressure meters.  Additionally, common pitfalls and ways to avoid them will be examined, such as leaky connections, pulsatile flows, and presence of bubbles.  Finally ways of designing microfluidic experiments to minimize the possibility of issues developing will be considered.


ALine, Inc.Integrated Fluid Distribution Manifolds as a Tool for Controlling Cell Culture and Organ-on-chip Platforms
Leanna Levine, Founder & CEO, ALine, Inc.

In this presentation we will provide an overview of integrated fluid distribution manifolds that enable delivery of reagents and culture media to organ on chip and cell culture platforms. These manifolds allow, automated control of culture conditions with no user intervention, for single chamber and multi-plex conditions, and can be used as a standalone component or as part of an integrated microfluidic cartridges.


Danilo TagleKeynote Presentation

3-D Bioprinting and Organ on Chips for Drug Discovery and Development
Danilo Tagle, Director, Office of Special Initiatives, National Center for Advancing Translational Sciences at the NIH (NCATS), United States of America

About 90 percent of potential new drugs fail in clinical trials because they are found to be ineffective or due to adverse events. This failure happens in large part because 2D in vitro assays, and animal models used during the drug discovery and development process do not accurately predict human physiological response. To address this critical for better predictive tools, NCATS is supporting programs for 3-D bioprinting of human cells in microplate format for drug screening and discovery, and organs on chips that can be used for safety and efficacy assessments of the candidate drugs.


Dan HuhKeynote Presentation

Microengineered Physiological Biomimicry: Human Organs-on-Chips
Dan Huh, Associate Professor of Bioengineering and Wilf Family Term Endowed Chair, University of Pennsylvania, United States of America

Human organs are complex living systems in which specialized cells and tissues are assembled in various patterns to carry out integrated functions essential to the survival of the entire organism. A paucity of predictive models that recapitulate the complexity of human organs and physiological systems poses major technical challenges in virtually all areas of life science and technology. This talk will present interdisciplinary research efforts to develop microengineered biomimetic models that reconstitute complex structure, dynamic microenvironment, and physiological function of living human organs. Specifically, I will talk about i) bioinspired microsystems that mimic the structural and functional complexity of the living human lung in health and disease, ii) an organ-on-chip microdevice that emulates the ocular surface of the human eye, and iii) microengineered physiological models of human reproductive organs.


Networking Reception in the Exhibit Hall with Beer and Wine. Meet the Exhibitors and Network with Your Colleagues


Close of Day 1 of the Conference.

Friday, 5 October 2018


Morning Coffee and Breakfast Pastries in the Exhibit Hall


Increasing Complexity of a Brain-on-a-Chip Device and Associated Neuronal Cultures
David Soscia, Biotechnology Engineer, Lawrence Livermore National Laboratory, United States of America

An in vitro brain-on-a-chip platform utilizing multi-electrode arrays (MEA) holds promise as a noninvasive experimental approach for evaluating toxicity of chemicals, validating new pharmaceutical drugs, and understanding neurological disease in humans.  Often, these devices contain a monolayer of a single purified primary neuronal cell type.  While these primary cultures can provide key insights into neuronal response and function, they fail to recapitulate in vivo cellular and molecular complexity as they lack representation and organization from multiple brain regions, as well as supporting glia.  Here, we present developments toward a more intricate in vitro system through advanced engineering and increased biological complexity.  A novel, removable cell seeding insert was developed to deposit neurons from different brain regions into separate regions of a substrate without the use of permanent physical barriers or chemical surface modifications.  Using the insert, we deposited primary rat cortical and hippocampal neurons into distinct regions of a custom 60-channel MEA.  Electrophysiology measurements were compared between the two systems over several weeks in vitro.  For the regionalized cell cultures, electrophysiology measurements demonstrated that while key firing characteristics were preserved for each neuronal type, some burst features were altered when the cells were co-cultured and able to form direct connections.  Separately, we evaluated the cellular activity of primary rat neuronal cultures cultured on the MEA containing additional supporting glial cell types (e.g., astrocytes and oligodendrocytes). For cultures containing glial cells, significant differences in electrophysiology responses were observed as cell culture complexity increased, including an earlier firing response and increased burst rate. Immunocytochemistry was used to identify each cell type, evaluate cell morphology, and assess the phenotypic state of supporting oligodendrocytes and astrocytes. These results suggest that a more complex brain-on-a-chip platform may provide additional insight and relevance to the in vitro brain model and will be validated using chemical challenges. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344 through LDRD award 17-SI-002.


AlveoliX AGA Breathing Human Lung-on-Chip Array For Drug Transport and Safety Studies
Janick Stucki, CEO and Technical Director, AlveoliX AG

Organs-on-chip (OOC) are widely seen as the next generation of in-vitro models. In contrast to standard cell culture systems, based on static 2D and 3D tissue systems, they additionally allow to better model the dynamic biomechanical microenvironment of specific organs. However, for the successful implementation of OOC in drug safety assessment and preclinical decision making, it is also important to develop easy to handle OOC systems. The breathing lung-on-chip array is based on a two-part design and equipped with a passive medium exchange mechanism. This allows ease of use and the precise control of the ultra-thin, elastic and porous PDMS membrane. The 96-well plate footprint of the chip and the array of 12 independent lung-on-chips increases experimental throughput and allows compatibility with standard laboratory equipment that highly facilitates its adoption in commercial use. By modelling a healthy alveolus-on-chip, we could show that primary alveolar epithelial cells from patients cultured at the air-liquid-interface and exposed to a physiological cyclic mechanical stress preserves their typical alveolar epithelial phenotype and their barrier function. Long-term co-culturing of epithelial and endothelial cells lead to an increased barrier functionality. Together with our cooperation partners we are working on different lung disease models such as acute lung injury, lung fibrosis and COPD. Additionally, we are constantly adapting our system for new applications such as exposure set-ups or automated stiffness and surfactant measurements.


University of California San DiegoApplications of Brain-Model Technology to Study Neurodevelopmental Disorders
Cleber Trujillo, Project Scientist, University of California San Diego

The complexity of the human brain permits the development of sophisticated behavioral repertoires, such as language, tool use, self-awareness, and consciousness. Understanding what produces neuronal diversification during brain development has been a longstanding challenge for neuroscientists and may bring insights into the evolution of human cognition. We have been using stem cell-derived brain model technology to gain insights into several biological processes, such as human neurodevelopment and autism spectrum disorders. The reconstruction of human synchronized network activity in a dish can help to understand how neural network oscillations might contribute to the social brain. Furthermore, we found that the Methyl-CpG-binding protein 2 (MECP2) is essential for the emergence of network oscillations, suggesting that functional maturation might be compromised at early stages of neurodevelopment in MECP2-related disorders, such as Rett syndrome, autism, and schizophrenia. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography. Our model provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex.


Integrated Surface TechnologiesTailored Chemistry of Nano-Materials for Creating Stable and Robust Platform Environments
Jeff Chinn, Chief Technical Officer, Integrated Surface Technologies

Surface engineering techniques through to use of specialized molecular chemistries can be used to develop or mitigate a wide range of functional properties, including physical, chemical, fluid flow, electrical, and corrosion-resistant properties. Almost all types of materials including metals, semiconductors, ceramics, polymers, and composites can be coated with molecular films to alter their surface states. Common surface engineered properties of interest often include: control of surface energies (hydrophobicity, hydrophilicity, anti-fouling), chemical grafting (functional groups –NH2, -OH, -COOH, -SH2, etc.), molecular level cleaning, surface activation, adhesion promotions (chemical activation for bonding, immobilizing DNA) and preservation (corrosion inhibitors, moisture barriers). These nano-scaled films can be engineered into many unique bio-compatible coatings. In this talk, we will review the basics of molecular coatings that are commonly used and a technique to applied and to control of surface properties for applications like micro-fluidics, genomics, PCR and others.


Coffee Break and Networking in the Exhibit Hall


John WikswoKeynote Presentation

Scientific, Engineering, and Translational Intersections and Trajectories: Organs-on-Chips, Organoids, Stem Cells, Microfluidics, Well Plates, Acoustics, and Multi-Omics
John Wikswo, Gordon A. Cain University Professor, A.B. Learned Professor of Living State Physics; Founding Director, Vanderbilt Institute for Integrative Biosystems, Vanderbilt University, United States of America

As organs-on-chips, organoids, induced pluripotent stem cells, and multi-omics become more widely integrated into the breadth of biology, pharmacology, and toxicology, it is important to understand the intrinsic capabilities and limitations of each approach and their supporting technologies, how they compete with or complement each other, what questions each is best suited to answer, and the associated challenges and opportunities. A comparison should consider issues of spatial scale, cost, sensitivity, ease of use, and assay speed. Economically significant choices, for example between high and low throughput approaches, single versus multiple organs or tissues, and targeted versus untargeted multi-omic analyses, depend upon the questions being asked, the budget, and the anticipated value of the answers. Ultimately, the greatest return on the substantial investment in these technologies may be amplified by a better understanding of technological and scientific intersections and trajectories and how to optimize the translation of each approach to address pressing scientific and medical questions.


George TruskeyKeynote Presentation

Human Microphysiological Systems for Disease Modeling
George Truskey, R. Eugene and Susie E. Goodson Professor of Biomedical Engineering, Duke University, United States of America

Human microphysiological systems that use cells from individuals with a range of disease can address limitations of existing animal models that incompletely replicate the disease phenotype.  We have cultured primary and induced pluripotent stem (iPS) cells to model features of a genetic disease, Hutchison-Gilford Progeria Syndrome (HGPS), a rare, accelerated aging disorder caused by an altered form of the lamin A (LMNA) gene termed progerin, exhibited expression of progerin.  Smooth muscle cells and endothelial cells differentiated from iPS cells maintained key features of the mature phenotype for a number of passages. Cells derived from patients with HGPS showed reduced growth rate and increased cell death.  Since the major cause of death in HGPS arises from accelerated atherosclerosis, we developed an arteriole-scale endothelialized  tissue engineered blood vessel (TEBV) with inner diameter of 800 µm.  eTEBVs fabricated with smooth muscle cells from individuals with HGPS show reduced vasoactivity, increased medial wall thickness, increased calcification and apoptosis in comparison to eTEBVs fabricated with smooth muscle cells from normal individuals or primary MSCs.  Both the endothelium and smooth muscle cells contributed to disease pathology.  Treatment with a number of compounds being considered for clinical trials reversed the disease progression and improved  the cellular content and function of the eTEBVs.  These results indicate that iPS cells can  be differentiated   to a functional vascular cells and that human eTEBVs can be used to model diseases in vitro.  This approach has been applied to other disease models.


Ali KhademhosseiniKeynote Presentation

Emerging Organ Models and Organ Printing for Regenerative Medicine
Ali Khademhosseini, Professor, Department of Bioengineering, Department of Radiology, Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, United States of America

Engineered materials that integrate advances in polymer chemistry, nanotechnology, and biological sciences have the potential to create powerful medical therapies. Our group aims to engineer tissue regenerative therapeutics using water-containing polymer networks called hydrogels that can regulate cell behavior. Specifically, we have developed photo-crosslinkable hybrid hydrogels that combine natural biomolecules with nanoparticles to regulate the chemical, biological, mechanical and electrical properties of gels. These functional scaffolds induce the differentiation of stem cells to desired cell types and direct the formation of vascularized heart or bone tissues. Since tissue function is highly dependent on architecture, we have also used microfabrication methods, such as microfluidics, photolithography, bioprinting, and molding, to regulate the architecture of these materials. We have employed these strategies to generate miniaturized tissues. To create tissue complexity, we have also developed directed assembly techniques to compile small tissue modules into larger constructs. It is anticipated that such approaches will lead to the development of next-generation regenerative therapeutics and biomedical devices.


Networking Lunch in the Exhibit Hall -- Meet the Exhibitors and View Posters


Abraham LeeKeynote Presentation

Vascularized Microphysiological Systems
Abraham Lee, Chancellor’s Professor, Biomedical Engineering & Director, Center for Advanced Design & Manufacturing of Integrated Microfluidics, University of California-Irvine, United States of America

Introduction to the microfluidic engineering of vascularized microphyiological systems that mimic the in vivo circulatory system at the microscale.  This in vitro model system can be used to screen cancer drugs with vascularized micro organs (VMO) and vascularized micro tumors (VMT).


Organs-on-a-Chip Mimicking Physiological Parameters For Pharmacokinetic Studies
Hiroshi Kimura, Professor, Micro/Nano Technology Center, Tokai University, Japan

Maintenance and replication of physiological functions of cells cultured in vitro are extremely difficult in conventional cell-based assay methods during life science and medical applications. Microfluidics is an emerging technology with the potential to provide integrated environments for maintenance, control, and monitoring the environment around cells. We work mainly in fundamental technologies of a microfluidic device and system, and their applications to biological sciences including Organ(s)-on-chips. In this presentation, we introduce integrated microfluidic platforms, which allow precise control of the cell culture environment on Organ(s)-on-chips. A physiological environment in vitro can be replicated by fabrication of microstructures and control of microfluidics in these devices. Moreover, functional components, such as sensors, valves and pump, can be integrated into the devices by microfabrication methods. We performed cell-based assays to evaluate the function of these devices. Because cells cultured in vitro could be maintained and measured, these devices may be applied to medical, pharmaceutical and biological sciences.


Striated Muscle Disease Modeling on a Chip
Megan L McCain, Assistant Professor of Biomedical Engineering and Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, United States of America

Cardiac and skeletal muscle research has traditionally been limited to model systems that lack throughput and/or relevance to native human tissues, such as animal models or simplified cell cultures with minimal functional outputs. The reliance on these platforms has limited our ability to establish human disease mechanisms, identify effective therapeutic targets, and efficiently screen drugs for functional efficacy. In this talk, I will describe our efforts in integrating tunable biomaterials, microfabrication techniques, and human cells (including stem cell derivatives) to engineer scalable models of human cardiac and skeletal muscle tissues with quantitative functional outputs. I will also describe how we are leveraging these platforms to model acquired and inherited forms of striated muscle diseases.


Construction of Organ-on-a-Chip Models For Pathological/Pharmacological Research
Shengli Mi, Associate Professor, Biomanufacturing Engineering Laboratory, Tsinghua University-Shenzhen, China

Organ-on-chips refer to the cell culture devices based on microfluidic technology to simulate the physiological functions and behaviors of tissues and organs through arranging living cells in a micrometer-sized chamber and the continuous supply of cell culture media. Organ-on-chips haves two main application directions: one is to study physiological or pathological mechanisms, and the other is to perform drug research and development based on the functions of organs. Here we mainly introduce our work from three aspects: the construction of a liver model based on a microfluidic chip, the microfluidic devices for tumor migration research, and the construction of a multi-organ system for liver metabolism anticancer drug testing.


Afternoon Coffee Break and Networking in the Exhibit Hall


Engineering Control for Endothelial Permeability in Microfluidic Vessel Bifurcation System
Shaurya Prakash, Associate Professor, Department of Mechanical and Aerospace Engineering, The Ohio State University, United States of America

Endothelial barrier function is known to be regulated by a number of molecular mechanisms; however, the role of biomechanical signals associated with blood flow is comparatively less explored. Biomimetic microfluidic models comprised of vessel analogues that are lined with endothelial cells (ECs) have been developed to help answer several fundamental questions in endothelial mechanobiology. However, previously described microfluidic models have been primarily restricted to single straight or two parallel vessel analogues, which do not model the bifurcating vessel networks typically present in physiology. Therefore, the effects of hemodynamic stresses that arise due to bifurcating vessel geometries on ECs are not well understood. Here, we introduce and characterize a microfluidic model that mimics both the flow conditions and the endothelial/extracellular matrix (ECM) architecture of bifurcating blood vessels to systematically monitor changes in endothelial permeability mediated by the local flow dynamics at specific locations along the bifurcating vessel structure. We show that bifurcated fluid flow (BFF) that arises only at the base of a vessel bifurcation with a stagnation pressure of ~38 dyn/ cm2 and approximately zero shear stress induces significant decrease in EC permeability compared to the static control condition in a nitric oxide (NO)-dependent manner. Similarly, intravascular laminar shear stress (LSS) (3 dyn cm-2) oriented tangential to ECs located downstream of the vessel bifurcation also causes a significant decrease in permeability compared to the static control condition via the NO pathway. In contrast, co-application of transvascular flow (TVF) (~1 µm s-1) with BFF and LSS rescues vessel permeability to the level of the static control condition, which suggests that TVF has a competing role against the stabilization effects of BFF and LSS. Recent investigations have also shown use of external electrical stimulation modulates endothelium permeability. These findings introduce BFF at the base of vessel bifurcations as an important regulator of vessel permeability and suggest a mechanism by which local flow dynamics and engineering controls can potentially assist in manipulation of vascular function in vivo.


Leaf-Inspired Microvascular Patterns
Kara McCloskey, Associate Professor, University of California-Merced, United States of America

The vascularization of tissue grafts is critical for maintaining viability of the cells within a transplanted graft.  A number of strategies are currently being investigated including very promising microfluidics systems. We explored the potential for generating a vasculature-patterned endothelial cells (EC) that could be integrated into distinct layers between sheets of primary cells.  Bioinspired from the leaf veins, we generated a reverse mold with a fractal vascular-branching pattern that models the unique spatial arrangement over multiple length scales that precisely mimic branching vasculature. By coating the reverse mold with 50µg/ml of fibronectin and stamping enabled selective adhesion of the human umbilical vein endothelial cells (HUVECS) to the patterned adhesive matrix, we show that a vascular-branching pattern can be transferred by microcontact printing.  Moreover, this pattern can be maintained transferred to a 3D hydrogel matrix and remains stable for up to 4 days. After 4 days, HUVECs can be observed migrating and sprouting into Matrigel. These printed vascular branching patterns, especially after transfer to 3D hydrogels, provide a viable alternative strategy to the prevascularization of complex tissues.


Close of Conference

Add to Calendar ▼2018-10-04 00:00:002018-10-05 00:00:00Europe/LondonOrgan-on-a-Chip and Body-on-a-Chip: In Vitro Systems Mimicking In Vivo Functions "Track A"