07:00 | Morning Coffee, Tea, Breakfast Pastries and Networking in the Exhibit Hall |
| Session Title: Emering 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 | Coffee, Tea and Networking in the Exhibit Hall |
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 Alex Robert Hopke, Research Scientist, Mass General Hospital (MGH), 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: Emerging Technologies and Applications Session and Late-Breaking Abstracts |
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13:30 | Active Materials for Remotely Regulating Complex, Multi-drug Delivery Profiles Stephen Kennedy, Assistant Professor of Biomedical and Chemical Engineering, University of Rhode Island, United States of America
Biological processes are characterized by a high degree of
spatiotemporal complexity and often manifest as a highly choreographed
sequence of biological events. Biomaterials such as hydrogels can
provide the localized deliveries needed to regulate biological
processes. However, they are incapable of regulating multi-drug delivery
profiles with the level of control required to regulate complex
biological processes (i.e., control over the timing, rate, and sequence
of multiple therapeutics). Moreover, the timings, rates, and sequences
delivered for particular therapies must likely be customized for
individual patients and may need to be changed in real-time according to
updated patient prognoses. This necessitates the need for on-demand
regulation over the timings, rates, and sequences of deliveries. Here,
we will present strategies for on-demand, remote control over the
timing, rate, and sequence of therapeutic deliveries from hydrogels
using electrically, magnetically, and ultrasonically active materials.
We will further describe biological scenarios where the deliveries
provided by traditional hydrogels can be greatly improved upon using
remotely activated materials (e.g., wound healing, tissue engineering,
chemotherapies). Finally, we will demonstrate that these remotely active
hydrogel materials have the potential to deliver optimized delivery
schedules in a wide range of therapeutic strategies. |
14:00 | 3D Printing Functional Materials & Devices Michael McAlpine, Kuhrmeyer Family Chair Professor of Mechanical Engineering, University of Minnesota, United States of America
The development of methods for interfacing high performance functional
devices with biology could impact regenerative medicine, smart
prosthetics, and human-machine interfaces. Indeed, the ability to
three-dimensionally interweave biological and functional materials could
enable the creation of devices possessing unique geometries,
properties, and functionalities. Yet, most high quality functional
materials are two dimensional, hard and brittle, and require high
crystallization temperatures for maximal performance. These properties
render the corresponding devices incompatible with biology, which is
three-dimensional, soft, stretchable, and temperature sensitive. We
overcome these dichotomies by: 1) using 3D printing and scanning for
customized, interwoven, anatomically accurate device architectures; 2)
employing nanotechnology as an enabling route for overcoming mechanical
discrepancies while retaining high performance; and 3) 3D printing a
range of soft and nanoscale materials to enable the integration of a
diverse palette of high quality functional nanomaterials with biology.
3D printing is a multi-scale platform, allowing for the incorporation of
functional nanoscale inks, the printing of microscale features, and
ultimately the creation of macroscale devices. This three-dimensional
blending of functional materials and ‘living’ platforms may enable
next-generation 3D printed devices. |
14:30 | Towards Bioprinting Industrialization Fabien Guillemot, CEO, Poietis, France
Bioprinting has been defined as “the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies”.
From a technological point of view, different bioprinting technologies have been developed so far. Recently, Laser-Assisted Bioprinting (LAB) technology has emerged as an alternative method to inkjet and bioextrusion methods, thereby overcoming some of their limitations (namely clogging of print heads or capillaries) to pattern living cells and biomaterials with a micron-scale resolution and high cell viability.
During this presentation, we will present current development on the industrialization of bioprinting process, namely in the context of manufacturing 3D skin models. |
15:00 | Bioprinting Multicellular Structure to Advance Vascularized 3D Tissue Engineering Alisa Morss, Associate Professor, Drexel University, United States of America
3D vascularized tissue engineering would enable mechanistic study of
healthy and diseased tissues, deliver a powerful platform for drug
screening, and potentially provide a replacement for diseased tissues.
The standard 3D tissue biofabrication process is layer-by-layer printing
of a bioink composed of cells within a matrix material. While this
process allows cells to be printed in a specific pattern to guide them
towards the desired 3D structure, it relies primarily on cellular
self-assembly into a 3D architecture that hopefully recapitulates the in
vivo tissue. Unfortunately, cellular self-assembly may take days or
weeks, may require complex spatial and temporal environmental cues, or
may not occur when two cell types are co-cultured together. Because of
these challenges, critical features of the tissue microenvironment
cannot be recapitulated, and therefore cell-cell interactions cannot be
studied in a physiologically relevant in vitro model. In this research,
we created a new bioprinting paradigm in which multicellular structures
that recapitulate in vivo architecture were used to create a 3D
vascularized breast cancer tissue model. The multicellular structures
were either grown in vitro prior to printing, or they were derived from
tissues (e.g., breast organoids). Our method decreases the time between
bioprinting and experimental assay from weeks to days; increases
physiological relevance by allowing the investigator to more precisely
control tissue architecture; and enables the use of primary human
tissues together with stromal cells and local extracellular matrix. |
15:30 | Stimuli-Responsive Therapeutic Bioinks for 3D Printing Rachael Oldinski, Assistant Professor, Department of Mechanical Engineering, University of Vermont, United States of America
The development of stimuli-responsive, or ‘smart’ biomaterials is
critical to the manipulative manufacturing of custom tissue engineering
scaffolds and implants. This talk will focus on the modification of a
seaweed derivative, alginate, for the design of sustainable materials
for tissue engineering construct development using 3D printing
technology. |
16:00 | Distilling Complexity to Advance Cardiac Tissue Engineering via 3D Bioprinting Brenda Ogle, Associate Professor of Biomedical Engineering, University of Minnesota, United States of America
The promise of cardiac tissue engineering is in the ability to design
replacement muscle for clinical therapy. Refined techniques for
deriving cardiac muscle cells from stem cells coupled with advanced
scaffolding techniques and 3D bioprinting are paving the way for a new
generation of simulated cardiac tissues. Recent success, ongoing
challenges and the role for industrial innovation in this growing field
will frame the content of this talk. |
16:30 | Glioblastoma Growth In Vitro 3D Modelling in an Adjustable Nanofiber-Hydrogel Hybrid Synthetic Scaffold Nikita Grigoryev, Adjunct Professor, NYU Tandon School of Engineering, United States of America
Glioblastoma multiforme (GBM), the most aggressive form of brain cancer that originates from glial type stem cells. Recent discoveries show that glioma growths show a mysterious property of mosaic tumor heterogeneity. Arising from the same common precursor, later stage tumors and individual migrating GBM cells exist in intermingled clonal subpopulations with mutually exclusive gene amplification contributing to an “epigenetic switch” that gives rise to malignant invasive subclones that escape the original tumor, heavily aggravating the disease progression and patient survival. Current in vitro models are typically far from physiological actuality and do not provide necessary 3D mechanobiological environment native to brain tissue. Our unique approach uses a marriage of patented electrospinning/nanofiber coating technique and dipping/cell trapping gelation method to create a layered scaffold construct for GBM in 3D. A hydrogel layer is built over a glass rod by dipping into either an acellular alginate solution (as a niche for cancerous invasion) or a cells-alginate suspension and is crosslinked by dipping into a cation solution. Subsequently, electrospun nanofibers are deposited directly onto each hydrogel layer for controllable nanotopography exterior similar that of native, while the hydrogel, as soft as brain, itself surrounds cells. We have confirmed successful growth, spread and invasion of originally seeded cells into acellular layers of our construct with an appearance of tumor-like structures resembling those found in-vivo. Our proposed adjustable 3D model is completely artificial and provides cells with mechanobiological nanoenvironment comparable to that of native tissue, while also allowing for easy cancerous growth tracking through transparent layers. |
17:00 | Sessile Drops on a Petri Dish for Biocompatible Cell-based Assays Aishah Prastowo, DPhil student, University of Oxford, United Kingdom
We developed a technique of performing cell-based assays in drop arrays on a standard tissue-culture polystyrene petri dish without further surface modification, and modelled the adsorption of serum in the cell media at the liquid and solid interfaces. |
17:30 | Close of Day 2 of the Conference. |