07:00 | Morning Coffee, Tea, Breakfast Pastries and Networking in the Exhibit Hall |
| Session Title: Emerging Themes in the Various BioEngineering Fields |
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08:00 | Bio-machines and Bio-manufacturing Xuanhe Zhao, Associate Professor, Massachusetts Institute of Technology (MIT), United States of America
While human tissues are mostly soft, wet and bioactive; machines are
commonly hard, dry and biologically inert. Bridging human-machine
interfaces is of imminent importance in addressing grand challenges in
health, security, sustainability and joy of living facing our society in
the 21st century. However, designing human-machine interfaces is
extremely challenging, due to the fundamentally contradictory properties
of human and machine. At MIT SAMs Lab, we propose to use tough
bioactive hydrogels to bridge human-machine interfaces. On one side,
bioactive hydrogels with similar physiological properties as tissues can
naturally integrate with human body, playing functions such as
scaffolds, catheters, drug reservoirs, and wearable devices. On the
other side, the hydrogels embedded with electronic and mechanical
components can control and response to external devices and signals. In
the talk, I will first present a bioinspired approach and a general
framework to design bioactive and robust hydrogels as the matrices for
human-machine interfaces. I will then discuss large-scale manufacturing
strategies to fabricate robust and bioactive hydrogels and hydrogel
electronics and machines, including 3D printing. Prototypes including
smart hydrogel band-aids, hydrogel robots and hydrogel circuits will be
further demonstrated. |
08:30 | Contracting 3D Printed Microtissues: Solid and Fluid Instabilities Thomas Angelini, Professor, Department of Mechanical and Aerospace Engineering, University of Florida, United States of America
Living cells are often dispersed in extracellular matrix (ECM) gels like collagen and Matrigel as minimal tissue models. Generally, large-scale contraction of these constructs is observed, in which the degree of contraction and compaction of the entire system correlates with cell density and ECM concentration. The freedom to perform diverse mechanical experiments on these contracting constructs is limited by the challenges of handling and supporting these delicate samples. Here, we present a method to create simple cell-ECM constructs that can be manipulated with significantly reduced experimental limitations. We 3D print mixtures of cells and ECM (collagen-I) into a 3D growth medium made from jammed microgels. With this approach, we design microtissues with controlled dimensions, composition, and material properties. We also control the elastic modulus and yield stress of the jammed microgel medium that envelops these microtissues. Similar to well-established bulk contraction assays, our 3D printed tissues contract. By contrast, the ability to create high aspect ratio objects with controlled composition and boundary conditions allows us to drive these microtissues into different regimes of physical instability. For example, a contracting tissue can be made to buckle as a whole or break up into droplets, depending on composition, size, and shape. These new instabilities may be employed in tissue engineering applications to anticipate the physical evolution of tissue constructs under the forces generated by the cells within. |
09:00 | Digital Biomanufacturing Enabling Multimode 4D Bioprinting William G Whitford, Life Science Strategic Solutions Leader, DPS Group, United States of America
3D bioprinting is the deposition of microchannels or droplets of a polymer and/or cell dispersion (bioink) to create 3D tissue-like structures that includes living cells. 4D bioprinting adds the extra dimension of time supporting the activity of smart, environmentally responsive biological structures and tissues. Many types of printing technologies are now used in bioprinting and each require appropriate manufacturing equipment, procedures and materials. Digital biomanufacturing orchestrates such concepts as increased monitoring, data handling, control algorithms, machine-learning and process modeling to a new level of process understanding, prediction and control. The IIoT, Big Data and Cloud technologies insure that the (historical and real-time) data being collected can be employed productively in richer data management, analysis and model generation. This leads to such values as more rapid process development as well as more comprehensive process control, automation and self-learning autonomation. Digital biomanufacturing will assist in the modeling and imaging required to recapitulate the (often personalized) complex and heterogeneous architecture of functional tissues and organs. It will also provide the required coordination and dynamic control of consequent complex tomographic information and models, multimode 3D printing and biofabrication processes, as well as such ancillary procedures as the environmental control of bioinks and nascent constructs. |
09:30 | | Keynote Presentation Layer-By-Layer Tissue Engineering Using Prefabricated Parts With Organ Cell Density Jeffrey Morgan, Professor of Medical Science and Engineering, Brown University, United States of America
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10:00 | | Keynote 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 powerful tools
to assess 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 and 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 predictors of human clinical response from
preclinical studies. |
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10:30 | Recombinant Human Collagen Based BioInk for 3D Bioprinting Nadav Orr, Vice President, R&D, CollPlant, Ltd. Israel
Recombinant human Type I collagen (rhCollagen) from engineered plants was developed as BioInk for 3D-Bioprinting. The BioInk, rhCollagen-MA, is compatible with all major printing technologies. It has superior rheological properties and demonstrated high biocompatibility with different cells types. |
11:00 | Autocatalytic Immune Reactions Daniel Irimia, Associate Professor, Surgery Department, Massachusetts General Hospital (MGH), Shriners Burns Hospital, and Harvard Medical School, United States of America
Neutrophil swarms protect healthy tissues by sealing off sites of infection. During swarming, neutrophils accumulate fast and in large numbers, under the control of mediators released by neutrophils already at the site. These mediators stimulate the arrival of additional neutrophils in an autocatalytic reaction that results in an exponential rate of swarm size increase. However, despite the autocatalytic reaction, not all 25 billion neutrophils from one’s body end up in one giant swarm. Thus, our recent goal was to identify the physiologic mediators that disrupt the autocatalytic reaction and stop the growth of neutrophil swarms. For this, we developed and validated large microscale arrays of microbe clusters, which can trigger the synchronized growth of thousands of swarms at once. The new tool enabled us to concentrate large amounts of swarm-released mediators in small volumes, and ultimately identify lipoxin A4 (LXA4) is a key mediator that disrupts the autocatalytic reactions, stops the growth of swarms, and ultimately leads to swarm dispersal. These and other insights from the study of neutrophil swarming will teach us how to design better strategies to combat infections and to control acute and chronic inflammatory diseases. |
11:30 | Hierarchical Biomaterials for Organ-on-a-Chip Devices and Tissue Engineering Frederik Claeyssens, Senior Lecturer, Materials Science and Engineering, University of Sheffield, United Kingdom
Natural tissues and organs are typically structured in a hierarchical fashion, in which the Extra-Cellular Matrix (ECM) provides a microporosity to optimally support cell growth while larger scale structures (e.g. vasculature and boundary layers) are incorporated to support the function and structure of the tissue and organ. To mimic this multiscale structuring in synthetic biomaterials we combine additive manufacturing with self-assembly. In this structuring technique the internal porosity is governed by self-assembly and the macroscopic structure is constructed by additive manufacturing. Emulsion templating is used as self-assembly technique to produce materials with a high microscale porosity. These emulsions can subsequently be used as photocurable resins for stereolithography, producing user-defined macroscale structures with a tissue-like microporosity. The mechanical properties of these materials can be varied via the changing the monomer ratio within the resin. Additionally, biodegradable scaffolds can be fabricated via polycaprolactone-based resins. We produce these hierarchical structured material in 3D structured materials such as woodpile-style scaffolds, microspheres with controllable diameter and as 3D microenvironments that can be integrated in standard poly-dimethylsiloxane (PDMS) based microfluidics. These scaffolds we currently investigate as a platform for organ-on-a-chip based devices and tissue engineering. |
12:00 | Networking Lunch in the Exhibit Hall |
| Session Title: Tissue Engineering and Bioprinting -- Research Trends and Applications Development |
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12:30 | Multi-Process Biofabrication for Bioinspired Tissue Models Yan Yan Shery Huang, Professor of BioEngineering, University of Cambridge, United Kingdom Elisabeth Gill, , University of Cambridge, United Kingdom
Multi-material and hybridized bioprinting technologies offer promising avenues to create mini-tissue models with enhanced heterogeneity and complexity. This presentation will first overview the application of 3D bioprinting and microfabrication techniques to fabricate tissue-on-a-chip systems for in vitro drug testing and screening. A layer-wise 3D biomimetic fibre patterning process will then be described. Multimaterial integration, with applications in building a generic cancer metastasis model is illustrated. |
13:00 | Scaffold-Free Tissue Engineering with ‘Regenova Bio 3D Printer’ Nicanor Moldovan, Associate Research Professor, Departments of Biomedical Engineering and Ophthalmology, Indiana University-Purdue University Indianapolis, United States of America
‘Scaffold-free’ tissue engineering relies on cells’ own ability to reconstitute complex bio-similar tissues, without the need of artificial materials as extracellular matrix equivalents (or ‘scaffolds’). I will discuss the uses in this regard of ‘Regenova Bio 3D Printer’ by Cyfuse Biomedical, capable to perform the skewering in micro-needles of cell spheroids for making larger 3D constructs, and modalities of ‘hybrid’ bioprinting as a means to overcome some of its limitations. |
13:30 | Designing Novel Biomaterial Inks For 3D Printing Murat Guvendiren, Assistant Professor, Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, United States of America
3D printing has become a significant tool to achieve structural complexity in fabricating biomaterial scaffolds and medical devices. However, the currently printed devices from biodegradable polymers only serve as a structural support. They permit but do not promote biological function, due to a lack of bioactivity. Our goal is to develop a novel biodegradable polymer family for extrusion-based printing, with user defined and tunable bioactivity. |
14:00 | Vascular and Myocardial Patches Using Cell Sheet Technology Joyce Wong, Professor of Biomedical Engineering and Materials Science & Engineering, Boston University, United States of America
A major challenge in vascular tissue engineering has been the ability to preserve the organization of native vessels in engineered tissues. We hypothesize that the structural organization of cells and extracellular matrix are critical for achieving functional mechanical properties of the tissue. In addition, our studies have demonstrated that cell phenotype is modulated by physiochemical properties of the underlying substrate. We have developed several methods to generate cell sheets that can be micropatterned and stacked in desired orientations. In addition, we have recently designed and fabricated a novel tissue stretching device that can measure the mechanical properties of single cell sheets. To our knowledge, the ability to test the mechanics of single cell sheets has not been reported yet; this will be important for computational models we are developing to aid in vascular tissue engineering. We will also discuss a novel cell source for myocardial patches and a bioMEMS device that can be used to assess how well specific cell sources perform in terms of physiological function under conditions relevant for patient implantation. |
14:30 | Injectable 3D Cryogels for Biomedical Applications Sidi Bencherif, Assistant Professor, Department of Chemical Engineering, Northeastern University, United States of America
Injectable biomaterials are increasingly being explored to minimize risks and complications associated with surgical implantation. Highly elastic cryogels with shape-memory properties have recently been developed to be injected through a small-bore needle with nearly complete geometric restoration once delivered. Cryogels displaying an interconnected macroporous structure can be molded to a variety of shapes and sizes, and may be optionally loaded with therapeutic agents or cells. These injectable scaffolds show great promise for various biomedical applications, including tissue engineering, cell transplantation, drug delivery, and cancer immunotherapy. |
15:00 | | Keynote Presentation Laser-Based 3-D Bioprinting Douglas Chrisey, Jung Chair of Materials Engineering and Professor of Physics, Tulane University, United States of America
Laser direct-write (LDW) printing was initially used for printing complex electronic materials in thin-films and circuits with spatial resolutions ~10 µm. This precise resolution and reproducibility made laser direct-write techniques attractive for adaptation to tissue engineering applications. Three-dimensional (3D) printing in tissue engineering requires the ability to deposit precise patterns of multicomponent and multiphase materials without degrading desirable properties such as porosity, homogeneity, or biological activity. Laser-based techniques can deposit patterns of biomaterials such as proteins, DNA, or living cells (individual or aggregated) with high spatial and volumetric resolution on the order of a picoliter or less, without compromising the viability of these delicate structures. This talk discusses how laser-based 3D printing techniques seek to address issues in tissue and organ printing. |
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15:30 | 3D Bioprinting Personalized Neural Tissue Stephanie Willerth, Professor and Canada Research Chair in Biomedical Engineering, University of Victoria and CEO – Axolotl Biosciences, Canada
The brain and spinal cord possess unique properties, including being able to send and receive electrical signals. My research group investigates novel methods for engineering neural tissue through the use of pluripotent stem cells and direct reprogramming of somatic cells, like fibroblasts and astrocytes. This talk will cover our recent advances to developing novel biomaterial strategies for engineering neural tissue from pluripotent stem cells and how they can be translated for applications in 3D printing. |
16:00 | Cardiovascular Tissue Engineering Using 3D Printing Technology Narutoshi Hibino, Assistant Professor, Cardiac Surgery, Johns Hopkins Hospital, United States of America
Cardiovascular disease is one of the leading causes of death worldwide despite the variety of medical, mechanical, and surgical strategies. We have developed novel 3D printing technologies that could change the practice of cardiovascular disease treatment, including patient specific 3D printed tissue engineered vascular graft and bio 3D printed cardiac tissue. I will discuss insights of these new 3D printing technology as well as challenges we need to overcome for future clinical application and commercialization. |
16:30 | Bioprinting and Stem Cells for Engineering Human Tissues Jinah Jang, Associate Professor, Pohang University of Science And Technology (POSTECH), Korea South
Engineered tissues with intrinsic geometry and appropriate cellular organization can produce high functional outcomes. Although the use of various micro-fabrication technologies for recapitulating tissue constructs has received considerable attention, the technical and operational capabilities in resembling native 3D tissue architecture remain to be overcome. In this sense, 3D printing technology is considered a useful technology with which to facilitate the construction of biomaterials and cells in desired organizations and shapes that have physiologically relevant geometry, complexity, and micro-environmental cues. The selection of biomaterial is the most critical part in this technology; yet, their cellular affinity has rarely been considered in the context of cell printing logistics. In this talk, I will introduce an advanced bioink, which made up with decellularized tissue extracellular matrix (dECM). The material is capable of providing an optimized microenvironment conducive to the growth and function of 3D engineered tissues. As a translational application, we demonstrated the therapeutic efficacy of stem cell-laden 3D engineered tissues, which can deliver cardiac stem cells with higher biological activity for the treatment of ischemic diseases. |
17:00 | Stereolithography Bioprinting of Cell-Laden Hydrogel Microarrays for High-Throughput Screening of Intracellular mRNA Delivery and Cell Response to Microenvironment Paula Menezes, Researcher, Oregon Health and Science University, United States of America
Here we present a novel high-throughput 3D bioprinting technology to fabricate stem cell laden-hydrogels with varying stiffness in a microarray arrangement. We validated this method by determining the osteogenic differentiation and how matrix physical properties influence delivery of mRNA-laden nanoparticles. |
17:30 | Development of 3D Model of Intestinal Epithelium to Study Intestinal Stem Cell Fate and Proliferation Justine Creff, Researcher, LAAS-CNRS, France
A new model of in vitro 3D intestinal epithelium has been developed based on high resolution 3D printed hydrogel structures. These scaffolds recapitulate key features of mouse intestinal crypts and villi and were validated using colorectal cancer cells. |
18:00 | Close of Day 2 of the Conference. |