Tag Archives: extracellular matrix

Accurate spatial orientation for regenerating cells

German scientists have developed a system that helps guide nerve cells into proper spatial alignmentswhen they are regenerating according to an April 5, 2017 news item on Nanowerk,

In many tissues of the human body, such as nerve tissue, the spatial organization of cells plays an important role. Nerve cells and their long protrusions assemble into nerve tracts and transport information throughout the body. When such a tissue is injured, an accurate spatial orientation of the cells facilitates the healing process. Scientists from the DWI – Leibniz Institute for Interactive Materials in Aachen developed an injectable gel, which can act as a guidance system for nerve cells.

An April 5, 2017 Leibniz Institute press release, which originated the news item, explains more about the research,

Inside the body, an extracellular matrix surrounds the cells. It provides mechanical support and promotes spatial tissue organization. In order to regenerate damaged tissue, an artificial matrix can temporally replace the natural extracellular matrix. This matrix needs to mimic the natural cell environment in order to efficiently stimulate the regenerative potential of the surrounding tissue. Solid implants, however, may impair remaining healthy tissue whereas soft, injectable materials allow for a minimal invasive therapy, which is particularly beneficial for sensitive tissues, such as the spinal cord. Unfortunately, up to now, artificial soft materials did not yet reproduce the complex structures and spatial properties of natural tissues.

A team of scientists, headed by Dr. Laura De Laporte from the DWI – Leibniz Institute for Interactive Materials, developed a new, minimal invasive material termed ‘Anisogel’. “If you aim to enhance the regeneration of damaged spinal cord tissue, you need to come up with a new material concept,” says Jonas Rose. He is a PhD student working on the Anisogel project. “We use micrometer-sized building blocks and assemble them into 3D hierarchically organized structures.” Anisogel consists of two gel components. Many, microscopically small, soft rod-shaped gels, incorporated with a low amount of magnetic nanoparticles, are the first component. Using a weak magnetic field, scientists can orient the gel rods, after which a very soft surrounding gel matrix is crosslinked, forming the structural guidance system. The gel rods, being stabilized by the gel matrix, maintain their orientation, even after removal of the magnetic field. Using cell culture experiments, the researchers demonstrate that cells can easily migrate through this gel matrix, and that nerve cells and fibroblasts orient along the paths provided by this guidance system.  A low amount of one percent gel rods inside the entire Anisogel volume is proven to be sufficient to induce linear nerve growth. The material, developed by the Aachen-based scientists, is the first injectable biomaterial, which assembles into a controlled oriented structure after injection and provides a functional guidance system for cells. “To meet the complex requirements of this approach, the project team includes researchers with very different areas of expertise,” says Laura De Laporte, whose research is supported by a Starting Grant of the European Research Council. “This interdisciplinary work is what makes this project so fascinating.”

“Although our cell culture experiments were successful, we are prepared to go a long way to translate our Anisogel into a medical therapy. In collaboration with the Uniklinik RWTH Aachen, we currently plan pre-clinical studies to further test and optimize this material,” Laura De Laporte explains.

Here’s a link to and a citation for the paper,

Nerve Cells Decide to Orient inside an Injectable Hydrogel with Minimal Structural Guidance  by Jonas C. Rose, María Cámara-Torres, Khosrow Rahimi, Jens Köhler, Martin Möller, and Laura De Laporte. Nano Lett., Article ASAP DOI: 10.1021/acs.nanolett.7b01123 Publication Date (Web): March 22, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

3D bioprinting: a conference about the latest trends (May 3 – 5, 2017 at the University of British Columbia, Vancouver)

The University of British Columbia’s (UBC) Peter Wall Institute for Advanced Studies (PWIAS) is hosting along with local biotech firm, Aspect Biosystems, a May 3 -5, 2017 international research roundtable known as ‘Printing the Future of Therapeutics in 3D‘.

A May 1, 2017 UBC news release (received via email) offers some insight into the field of bioprinting from one of the roundtable organizers,

This week, global experts will gather [4] at the University of British
Columbia to discuss the latest trends in 3D bioprinting—a technology
used to create living tissues and organs.

In this Q&A, UBC chemical and biological engineering professor
Vikramaditya Yadav [5], who is also with the Regenerative Medicine
Cluster Initiative in B.C., explains how bioprinting could potentially
transform healthcare and drug development, and highlights Canadian
innovations in this field.

WHY IS 3D BIOPRINTING SIGNIFICANT?

Bioprinted tissues or organs could allow scientists to predict
beforehand how a drug will interact within the body. For every
life-saving therapeutic drug that makes its way into our medicine
cabinets, Health Canada blocks the entry of nine drugs because they are
proven unsafe or ineffective. Eliminating poor-quality drug candidates
to reduce development costs—and therefore the cost to consumers—has
never been more urgent.

In Canada alone, nearly 4,500 individuals are waiting to be matched with
organ donors. If and when bioprinters evolve to the point where they can
manufacture implantable organs, the concept of an organ transplant
waiting list would cease to exist. And bioprinted tissues and organs
from a patient’s own healthy cells could potentially reduce the risk
of transplant rejection and related challenges.

HOW IS THIS TECHNOLOGY CURRENTLY BEING USED?

Skin, cartilage and bone, and blood vessels are some of the tissue types
that have been successfully constructed using bioprinting. Two of the
most active players are the Wake Forest Institute for Regenerative
Medicine in North Carolina, which reports that its bioprinters can make
enough replacement skin to cover a burn with 10 times less healthy
tissue than is usually needed, and California-based Organovo, which
makes its kidney and liver tissue commercially available to
pharmaceutical companies for drug testing.

Beyond medicine, bioprinting has already been commercialized to print
meat and artificial leather. It’s been estimated that the global
bioprinting market will hit $2 billion by 2021.

HOW IS CANADA INVOLVED IN THIS FIELD?

Canada is home to some of the most innovative research clusters and
start-up companies in the field. The UBC spin-off Aspect Biosystems [6]
has pioneered a bioprinting paradigm that rapidly prints on-demand
tissues. It has successfully generated tissues found in human lungs.

Many initiatives at Canadian universities are laying strong foundations
for the translation of bioprinting and tissue engineering into
mainstream medical technologies. These include the Regenerative Medicine
Cluster Initiative in B.C., which is headed by UBC, and the University
of Toronto’s Institute of Biomaterials and Biomedical Engineering.

WHAT ETHICAL ISSUES DOES BIOPRINTING CREATE?

There are concerns about the quality of the printed tissues. It’s
important to note that the U.S. Food and Drug Administration and Health
Canada are dedicating entire divisions to regulation of biomanufactured
products and biomedical devices, and the FDA also has a special division
that focuses on regulation of additive manufacturing – another name
for 3D printing.

These regulatory bodies have an impressive track record that should
assuage concerns about the marketing of substandard tissue. But cost and
pricing are arguably much more complex issues.

Some ethicists have also raised questions about whether society is not
too far away from creating Replicants, à la _Blade Runner_. The idea is
fascinating, scary and ethically grey. In theory, if one could replace
the extracellular matrix of bones and muscles with a stronger substitute
and use cells that are viable for longer, it is not too far-fetched to
create bones or muscles that are stronger and more durable than their
natural counterparts.

WILL DOCTORS BE PRINTING REPLACEMENT BODY PARTS IN 20 YEARS’ TIME?

This is still some way off. Optimistically, patients could see the
technology in certain clinical environments within the next decade.
However, some technical challenges must be addressed in order for this
to occur, beginning with faithful replication of the correct 3D
architecture and vascularity of tissues and organs. The bioprinters
themselves need to be improved in order to increase cell viability after
printing.

These developments are happening as we speak. Regulation, though, will
be the biggest challenge for the field in the coming years.

There are some events open to the public (from the international research roundtable homepage),

OPEN EVENTS

You’re invited to attend the open events associated with Printing the Future of Therapeutics in 3D.

Café Scientifique

Thursday, May 4, 2017
Telus World of Science
5:30 – 8:00pm [all tickets have been claimed as of May 2, 2017 at 3:15 pm PT]

3D Bioprinting: Shaping the Future of Health

Imagine a world where drugs are developed without the use of animals, where doctors know how a patient will react to a drug before prescribing it and where patients can have a replacement organ 3D-printed using their own cells, without dealing with long donor waiting lists or organ rejection. 3D bioprinting could enable this world. Join us for lively discussion and dessert as experts in the field discuss the exciting potential of 3D bioprinting and the ethical issues raised when you can print human tissues on demand. This is also a rare opportunity to see a bioprinter live in action!

Open Session

Friday, May 5, 2017
Peter Wall Institute for Advanced Studies
2:00 – 7:00pm

A Scientific Discussion on the Promise of 3D Bioprinting

The medical industry is struggling to keep our ageing population healthy. Developing effective and safe drugs is too expensive and time-consuming to continue unchanged. We cannot meet the current demand for transplant organs, and people are dying on the donor waiting list every day.  We invite you to join an open session where four of the most influential academic and industry professionals in the field discuss how 3D bioprinting is being used to shape the future of health and what ethical challenges may be involved if you are able to print your own organs.

ROUNDTABLE INFORMATION

The University of British Columbia and the award-winning bioprinting company Aspect Biosystems, are proud to be co-organizing the first “Printing the Future of Therapeutics in 3D” International Research Roundtable. This event will congregate global leaders in tissue engineering research and pharmaceutical industry experts to discuss the rapidly emerging and potentially game-changing technology of 3D-printing living human tissues (bioprinting). The goals are to:

Highlight the state-of-the-art in 3D bioprinting research
Ideate on disruptive innovations that will transform bioprinting from a novel research tool to a broadly adopted systematic practice
Formulate an actionable strategy for industry engagement, clinical translation and societal impact
Present in a public forum, key messages to educate and stimulate discussion on the promises of bioprinting technology

The Roundtable will bring together a unique collection of industry experts and academic leaders to define a guiding vision to efficiently deploy bioprinting technology for the discovery and development of new therapeutics. As the novel technology of 3D bioprinting is more broadly adopted, we envision this Roundtable will become a key annual meeting to help guide the development of the technology both in Canada and globally.

We thank you for your involvement in this ground-breaking event and look forward to you all joining us in Vancouver for this unique research roundtable.

Kind Regards,
The Organizing Committee
Christian Naus, Professor, Cellular & Physiological Sciences, UBC
Vikram Yadav, Assistant Professor, Chemical & Biological Engineering, UBC
Tamer Mohamed, CEO, Aspect Biosystems
Sam Wadsworth, CSO, Aspect Biosystems
Natalie Korenic, Business Coordinator, Aspect Biosystems

I’m glad to see this event is taking place—and with public events too! (Wish I’d seen the Café Scientifique announcement earlier when I first checked for tickets  yesterday. I was hoping there’d been some cancellations today.) Finally, for the interested, you can find Aspect Biosystems here.

Better technique for growing organoids taking them from the lab to the clinic

A Nov. 16, 2016 École Polytechnique Fédérale de Lausanne (EPFL) press release (also on EurekAlert) describes a new material for growing organoids,

Organoids are miniature organs that can be grown in the lab from a person’s stem cells. They can be used to model diseases, and in the future could be used to test drugs or even replace damaged tissue in patients. But currently organoids are very difficult to grow in a standardized and controlled way, which is key to designing and using them. EPFL scientists have now solved the problem by developing a patent-pending “hydrogel” that provides a fully controllable and tunable way to grow organoids. …

Organoids need a 3D scaffold

Growing organoids begins with stem cells — immature cells that can grow into any cell type of the human body and that play key roles in tissue function and regeneration. To form an organoid, the stem cells are grown inside three-dimensional gels that contain a mix of biomolecules that promote stem cell renewal and differentiation.

The role of these gels is to mimic the natural environment of the stem cells, which provides them with a protein- and sugar-rich scaffold called the “extracellular matrix”, upon which the stem cells build specific body tissues. The stem cells stick to the extracellular matrix gel, and then “self-organize” into miniature organs like retinas, kidneys, or the gut. These tiny organs retain key aspects of their real-life biology, and can be used to study diseases or test drugs before moving on to human trials.

But the current gels used for organoid growth are derived from mice, and have problems. First, it is impossible to control their makeup from batch to batch, which can cause stem cells to behave inconsistently. Second, their biochemical complexity makes them very difficult to fine-tune for studying the effect of different parameters (e.g. biological molecules, mechanical properties, etc.) on the growth of organoids. Finally, the gels can carry pathogens or immunogens, which means that they are not suitable for growing organoids to be used in the clinic.

A hydrogel solution

The lab of Matthias Lütolf at EPFL’s Institute of Bioengineering has developed a synthetic “hydrogel” that eschews the limitations of conventional, naturally derived gels. The patent-pending gel is made of water and polyethylene glycol, a substance used widely today in various forms, from skin creams and toothpastes to industrial applications and, as in this case, bioengineering.

Nikolce Gjorevski, the first author of the study, and his colleagues used the hydrogel to grow stem cells of the gut into a miniature intestine. The functional hydrogel was not only a goal in and of itself, but also a means to identify the factors that influence the stem cells’ ability to expand and form organoids. By carefully tweaking the hydrogel’s properties, they discovered that separate stages of the organoid formation process require different mechanical environments and biological components.

One such factor is a protein called fibronectin, which helps the stem cells attach to the hydrogel. Lütolf’s lab found that this attachment itself is immensely important for growing organoids, as it triggers a whole host of signals to the stem cell that tell it to grow and build an intestine-like structure. The researchers also discovered an essential role for the mechanical properties, i.e. the physical stiffness, of the gel in regulating intestinal stem cell behavior, shedding light on how cells are able to sense, process and respond to physical stimuli. This insight is particularly valuable – while the influence of biochemical signals on stem cells is well-understood, the effect of physical factors has been more mysterious.

Because the hydrogel is man-made, it is easy to control its chemical composition and key properties, and ensure consistency from batch to batch. And because it is artificial, it does not carry any risk of infection or triggering immune responses. As such, it provides a means of moving organoids from basic research to actual pharmaceutical and clinical applications in the future.

Lütolf’s lab is now researching other types of stem cells in order to extend the capacities of their hydrogel into other tissues.

Here’s a link to and a citation for the paper,

Designer matrices for intestinal stem cell and organoid culture by Nikolce Gjorevski, Norman Sachs, Andrea Manfrin, Sonja Giger, Maiia E. Bragina, Paloma Ordóñez-Morán, Hans Clevers, & Matthias P. Lutolf.  Nature (2016) doi:10.1038/nature20168 Published online 16 November 2016

This paper is behind a paywall.

‘Hotel for cells’ or minuscule artificial scaffolding units for plant tissue engineering

This is the first time I’ve seen an item about tissue engineering which concerns plant life.  An August 27, 2015 news item on Azonano describes the latest development with plant cells,

Miniscule artificial scaffolding units made from nano-fibre polymers and built to house plant cells have enabled scientists to see for the first time how individual plant cells behave and interact with each other in a three-dimensional environment.

These “hotels for cells” mimic the ‘extracellular matrix’ which cells secrete before they grow and divide to create plant tissue. [Note: Human and other cells also have extracellular matrices] This environment allows scientists to observe and image individual plant cells developing in a more natural, multi-dimensional environment than previous ‘flat’ cell cultures.

An August 26, 2015 University of Cambridge press release, which originated the news item, describes the research and mentions the pioneering technologies which made it possible,

The research team were surprised to see individual plant cells clinging to and winding around their fibrous supports; reaching past neighbouring cells to wrap themselves to the artificial scaffolding in a manner reminiscent of vines growing.

Pioneering new in vitro techniques combining recent developments in 3-D scaffold development and imaging, scientists say they observed plants cells taking on growth and structure of far greater complexity than has ever been seen of plant cells before, either in living tissue or cell culture.

“Previously, plant cells in culture had only been seen in round or oblong forms. Now, we have seen 3D cultured cells twisting and weaving around their new supports in truly remarkable ways, creating shapes we never thought possible and never seen before in any plant,” said plant scientist and co-author Raymond Wightman.

“We can use this tool to explore how a whole plant is formed and at the same time to create new materials.”

This ability for single plant cells to attach themselves by growing and spiralling around the scaffolding suggests that cells of land plants have retained the ability of their evolutionary ancestors – aquatic single-celled organisms, such as Charophyta algae – to stick themselves to inert structures.

While similar ‘nano-scaffold’ technology has long been used for mammalian cells, resulting in the advancement of tissue engineering research, this is the first time such technology has been used for plant cells – allowing scientists to glimpse in 3-D the individual cell interactions that lead to the forming of plant tissue.

The scientists say the research “defines a new suite of techniques” for exploring cell-environment interactions, allowing greater understating of fundamental plant biology that could lead to new types of biomaterials and help provide solutions to sustainable biomass growth.

“While we can peer deep inside single cells and understand their functions, when researchers study a ‘whole’ plant, as in fully formed tissue, it is too difficult to disentangle the many complex interactions between the cells, their neighbours, and their behaviour,” said Wightman.

“Until now, nobody had tried to put plant cells in an artificial fibre scaffold that replicates their natural environment and tried to observe their interactions with one or two other cells, or fibre itself,” he said.

Co-author and material scientist Dr Stoyan Smoukov suggests that a possible reason why artificial scaffolding on plant cells had never been done before was the expense of 3D nano-fibre matrices (the high costs have previously been justified in mammalian cell research due to its human medical potential).

However, Smoukov has co-discovered and recently helped commercialise a new method for producing polymer fibres for 3-D scaffolds inexpensively and in bulk. ‘Shear-spinning’ produces masses of fibre, in a technique similar to creating candy-floss in nano-scale. The researchers were able to adapt such scaffolds for use with plant cells.

This approach was combined with electron microscopy imaging technology. In fact, using time-lapse photography, the researchers have even managed to capture 4-D footage of these previously unseen cellular structures. “Such high-resolution moving images allowed us to follow internal processes in the cells as they develop into tissues,” said Smoukov, who is already working on using the methods in this plant study to research mammalian cancer cells.

Here’s an image illustrating the research,

Plant cells twisting and weaving in 3-D cultures Credit: Smoukov/Wightman

Plant cells twisting and weaving in 3-D cultures
Credit: Smoukov/Wightman

Here’s a link to and a citation for the paper,

A 3-dimensional fibre scaffold as an investigative tool for studying the morphogenesis of isolated plant pells [cells?] by CJ Luo, Raymond Wightman, Elliot Meyerowitz, and Stoyan K. Smoukov. BMC Plant Biology 2015, 15:211 doi:10.1186/s12870-015-0581-7

This paper is open access.