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Functional 3D models have quickly captured the attention of the pharmaceutical industry. All agree these 3D models offer high content, high impact and high value. However, for wider implementation in R&D drug testing and screening labs, compatible higher-throughput 3D model platforms must be engineered to carry out research on the scale appropriate for drug discovery. Creating these more biologically relevant models requires a multidisciplinary approach and multidisciplinary expertise. Cambridge Healthtech Institute’s Third Annual Engineering Functional 3D Models meeting weaves together engineers, biologists, screening managers and pharmacologists. As with any model, each specialty provides insights into the complete system advancing drug discovery and development.
Sunday, November 16
5:00 pm Short Course Registration and Main Conference Pre-Registration
Monday, November 17
7:30 am Conference Registration and Morning Coffee
8:15 Welcome and Chairperson’s Opening Remarks (Sponsorship Opportunity Available)
KICKOFF KEYNOTE PRESENTATION
8:25 Personalized Reading and Writing of Organs
George Church, Ph.D., Professor, Genetics, Harvard Medical School; Professor, Health Sciences and Technology, Harvard and MIT; Founding Core Faculty Member, Platform Lead, Synthetic Biology, Wyss Institute for Biologically Inspired Engineering, Harvard University
We need better systems for testing small molecule, protein and nucleic acid therapeutics—ideally personalized organs, as can be achieved via iPSC, ePSC or SCNT-ESCs. One or more variants of unknown significance can be tested for a causal role by using CRISPR genome editing and a variety of simple cell types and complex organs and systems derived by epigenomic reprogramming. This engineering system is especially useful in leveraging the world’s only open-access (with very well-characterized -omic and medical data) human subjects (personalgenomes.org). The faithfulness of the organ system models, as well as their drug responses, can be checked using fluorescent in situ sequencing (FISSEQ).
9:05 Models of Complex Human Disease in 3D Skin-Like Tissues
Jonathan Garlick, D.D.S, Ph.D., Professor, Oral Pathology, School of Dental Medicine, Tufts University; Director, Center for Integrated Tissue Engineering and Professor, Tufts School of Medicine, School of Engineering and Sackler School of Graduate Biomedical Sciences
Chronic diseases like diabetes are characterized by complex microenvironments in which disease complications arise. The screening of novel treatments, like chronic wounds, must use 3D tissue platforms that better mimic in vivo conditions. We describe the development of 3D tissues that mimic non-healing wounds by incorporating cells derived from chronic wounds and iPSCs. This provides “disease in a tissue” platforms that can more efficiently translate in vitro findings into clinical applications.
9:35 Toward a 3D Model of Human Brain Development for Studying Gene/Environment Interactions
Helena Hogberg, Ph.D., Research Associate, Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University
Microphysiological systems (MPS) could generate more complex in vitro human models that better simulate organ biology and function. iPSCs allow cellular studies of individuals with different genetic backgrounds. Application of iPSCs from different donors in MPS improves understanding of disease mechanisms, drug development, toxicology and medicine. For a brain-on-a-chip, we established a 3D model from healthy and Down Syndrome donors’ iPSCs with mRNA and microRNA levels evaluated during eight weeks of neural differentiation.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:30 “Body-on-a-Chip”: A Multi-Organ Microdevice for Drug Development
Michael L. Shuler, Ph.D., Professor, Chemical Engineering and Chair, Biomedical Engineering, School of Chemical and Biomolecular Engineering, Cornell University
Our goal is the development of a human-based in vitro system that reduces dependency on animal testing and makes more effective predictions of human response to drugs. By combining microfabrication and cell culture, we have constructed devices known as “Body-on-a-Chip” systems. These devices are physical replicas of a physiologically based pharmacokinetic (PBPK) model where tissue-engineered constructs replace the differential equations for each organ in the PBPK.
11:00 Organs-on-a-Chip: The Future of Personalized Medicine?
Kevin E. Healy, Ph.D., Jan Fandrianto Distinguished Chair in Engineering; Professor and Chair, Bioengineering; Professor, Materials Science and Engineering, University of California, Berkeley
Drug safety and efficacy testing are hampered by high failure rates attributed to reliance on non-human animal models. We have developed integrated in vitro models of human cardiac and liver tissue based on normal and patient-specific hiPS cell populations differentiated into cardiomyocytes or hepatocytes, respectively. Our in vitro integrated physiological system has the potential to significantly reduce both the cost and duration of bringing a new drug candidate to market.
11:30 Sponsored Presentation (Opportunity Available)
12:00 pm Close of Session
12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:30 Chairperson’s Remarks
Rosemarie Hunziker, Ph.D., Director, Tissue Engineering and Regenerative Medicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health
1:35 2D Versus 3D: When to Make the Switch
Christopher S. Chen, M.D., Ph.D., Professor, Biomedical Engineering, Boston University and Wyss Institute for Biologically Inspired Engineering, Harvard University
The structure, mechanics and dimensionality of an extracellular matrix have fundamental effects on the phenotype of mammalian cells. This presentation examines how these physical cues can drive cell signaling and function, and how we can use these insights to develop in vitro cultures that better mimic in vivo biology for both discovery and development applications.
2:05 Customized 3D Cell Cultures and Assays Showcase (Sponsorship Opportunities Available)
All agree that 3D cell models that are morphologically and functionally similar to native tissue hold the potential to improve in vitro cell-based assays. However, it is important to note that there is no one-size-fits-all solution; each cell type requires a different environment and different assays to screen them. This session showcases companies that are driving cell culture and screening assays into the new dimension of studying health vs. disease and drug response.
2:05 Talk Title to be Announced
David Mann, Ph.D., Product Manager, Cellular Dynamics International
2:25 Showcase #2
2:45 Showcase #3
3:05 Refreshment Break in the Exhibit Hall with Poster Viewing
3:45 Organs-on-Chips to Screen for Drug Efficacy and Toxicity
Kristin Fabre, Ph.D., Scientific Program Manager, NCATS, National Institutes of Health
The Microphysiological Systems Program, comprised of an MPS Consortium of academic and government entities, aims to bioengineer platforms (or chips) that mimic human organ systems. These platforms help predict efficacy and toxicity of candidate compounds faster, cheaper and with fewer animal models than current methods. The project’s goal is to incorporate human iPSC-derived cell sources (inducible pluripotent stem cells) into corresponding organ modules and create an integrated Human-on-a-Chip to study drug response within human bodies.
4:30 Organs-on-Chips: Highly Functional Microphysiological Systems to Predict Human Physiology and Pathobiology
Geraldine A. Hamilton, Ph.D., Senior Staff Scientist, Wyss Institute for Biologically Inspired Engineering, Harvard University
This presentation focuses on our novel biomimetic microsystem technologies and their potential application in predicting efficacy, safety and mechanism of action for new drugs, chemicals and cosmetics. Human organs-on-chips provide exciting new approaches to attack fundamental questions in biology and develop smart in vitro surrogates. This technology also offers a more human-relevant alternative to current animal-based approaches for disease model development.
5:15 Welcome Reception in the Exhibit Hall with Poster Viewing
6:15 Short Course Registration
Tuesday, November 18
7:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
8:30 Chairperson’s Remarks
Jonathan Garlick, D.D.S, Ph.D., Tufts University
8:35 Microengineering Hydrogels for Tissue Engineering Applications
Nasim Annabi, Ph.D., Instructor, Brigham and Women’s Hospital and Harvard Medical School
Micro- and nanoscale technologies are powerful techniques in addressing the current challenges in tissue engineering. These technologies have allowed for an unprecedented ability to control cell-microenvironment interactions. Our group has been actively involved in merging advanced biomaterials and microscale technologies to create 3D vascularized tissues. I outline our work in the development of microscale hydrogels to modulate cell-microenvironment interactions for tissue engineering applications.
9:05 Development of 3D Tissue Engineering Platforms for Personalized Cancer Therapeutics
Jenny Zilberberg, Ph.D., Assistant Scientist, The John Theurer Cancer Center, Hackensack University Medical Center
I present work on the development of a novel 3D tissue engineering platform that uses microfluidic technology to provide a physiologically relevant in vitro model to study cancers that reside in or metastasizes to the bone/bone marrow microenvironment, and could offer a suitable tool to perform chemosensitivity analysis and develop new cancer therapeutics.
9:35 Micro- and Nanoscale 3D Bioprinting for Functional Tissue Scaffolds
Shaochen Chen, Ph.D., Professor, NanoEngineering and Bioengineering, University of California, San Diego
I discuss my laboratory’s recent research efforts in femtosecond laser nanoprinting and projection 3D bioprinting to create 3D scaffolds using a variety of biomaterials. These 3D biomaterials are functionalized with precise control of microarchitecture, mechanical properties (e.g., stiffness and Poisson’s ratio) and growth factors. Such functional biomaterials allow us to investigate cell-microenvironment interactions at nano- and microscales in response to integrated physical and chemical stimuli.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Synthetic Capillaries: Engineering Microscale Blood Flow
Gregory Timp, Ph.D., Keough-Hesburgh Professor of Engineering and Systems Biology, Colleges of Science and Engineering, University of Notre Dame
Capillaries pervade human physiology. The lack of perfusion associated with capillaries is especially problematic in thick engineered tissue because it leads to hypoxic stress and necrosis. We show it is possible to create in vitro a microenvironment that emulates a capillary using “live cell lithography” by controlling the type and position of cells on a composite hydrogel scaffold. These constructs support the forces and nutrient gradients associated with blood flow.
11:15 A New 3D Model to Test Clonal Expansion and Treatment Efficacy of Potential Drugs for Multiple Myeloma
Bhagavathi Narayanan, Ph.D., Associate Professor, Environmental Medicine, NYU School of Medicine
Methacrylated hyaluronic acid-based 3D hybrid hydrogel provides a unique ex vivo system that mimics a physiologically similar human microenvironment suitable for examining the behavior of invasive cancer cells. Most important, 3D hydrogel with differences in matrix composition and stiffness represents a new version of 3D model that supports clonal expansion, migration, multiplication and differentiation of cancer cells. Clonal expansion within encapsulated hydrogels enables assessment of the treatment efficacy of potential drugs.
CLOSING KEYNOTE PRESENTATION
11:45 Scaling and Systems Biology for Integrating Multiple Organs-on-a-Chip
John P. Wikswo, Ph.D., Founding Director, Vanderbilt Institute for Integrative Biosystems Research and Education and Gordon A. Cain University Professor, Biomedical Engineering, Vanderbilt University
Determination of the toxicity of drugs, consumer products and industrial chemicals will benefit from quantitative systems approaches to pharmacology and toxicology. By supporting heterogeneous cell populations and complex 3D extracellular matrices, tissue-engineered organs-on-chips and human organ constructs provide in vitro organotypic culture models for tissue-scale toxicology that are more realistic than static, planar, monolayer, immortal monocultures. Properly coupled, they create a new class of in vitro microphysiological systems models. Dr. Wikswo was recently published in Experimental Biology and Medicine, a Sage Publication, on The relevance and potential roles of microphysical systems in biology and medicine.
12:30 pm Close of Engineering Functional 3D Models and Organotypic Culture Models for Toxicology Conferences