Tag Archives: bioprinting

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.

Japanese art of flower arranging (Ikebana) leads to brain organoids

Testing brain cells in a petri dish doesn’t necessarily tell you what’s going on in a 3D brain according to Christian Naus, a professor in the department of cellular and physiological sciences at the University of British Columbia (UBC; Canada). A Dec. 5, 2016 UBC news release received via email (also available on EurekAlert) elaborates on Naus’ work,

The ancient Japanese art of flower arranging was the inspiration for a groundbreaking technique to create tiny “artificial brains” that could be used to develop personalized cancer treatments.

The organoids, clusters of thousands of human brain cells, cannot perform a brain’s basic functions, much less generate thought. But they provide a far more authentic model – the first of its kind – for studying how brain tumours grow, and how they can be stopped.

“This puts the tumour within the context of a brain, instead of a flat plastic dish,” said Christian Naus, a professor in the department of cellular and physiological sciences, who conceived the project with a Japanese company that specializes in bioprinting. He shared details about the technique at November’s annual Society for Neuroscience conference in San Diego. “When cells grow in three dimensions instead of two, adhering only to each other and not to plastic, an entirely different set of genes are activated.”

Naus studies glioblastoma, a particularly aggressive brain cancer that usually takes root deep inside the brain, and easily spreads. The standard care is surgery, followed by radiation and/or chemotherapy, but gliomas almost always return because a few malignant cells manage to leave the tumour and invade surrounding brain tissue. From the time of diagnosis, average survival is one year.

The idea for creating a more authentic model of glioblastoma originated when Naus partnered with a Japanese biotechnology company, Cyfuse, that has developed a particular technique for printing human tissues based on the Japanese art of flower arranging known as ikebana. In ikebana, artists use a heavy plate with brass needles sticking up, upon which the stems of flowers are affixed. Cyfuse’s bioprinting technique uses a much smaller plate covered with microneedles.

Working with Naus and research associate Wun Chey Sin, Kaori Harada of Cyfuse skewered small spheres of human neural stem cells on the microneedles. As the stem cells multiplied and differentiated into brain tissue, they merged and formed larger structures known as organoids, about two millimetres to three millimetres in diameter. Although the organoids lack blood vessels, they are small enough to allow oxygen and nutrients to permeate the tissue.

“The cells make their own environment,” said Naus, Canada Research Chair in Gap Junctions and Neurological Disorders. “We’re not doing anything except printing them, and then they self-assemble.”

The team then implanted cancerous glioma cells inside the organoids. Naus found that the gliomas spread into the surrounding normal cells.

Having shown that the tumour invades the surrounding tissue, Naus envisions that such a technique can be used with a patient’s own cells – both their normal brain cells and their cancerous cells – to grow a personalized organoid with a glioma at its core, and then test a variety of possible drugs or combinations of treatment to see if any of them stop the cancer from growing and invading.

“With this method, we can easily and authentically replicate a model of the patient’s brain, or at least some of the conditions under which a tumour grows in that brain,” said Naus. “Then we could feasibly test hundreds of different chemical combinations on that patient’s cells to identify a drug combination that shows the most promising result, offering a personalized therapy for brain cancer patients.”

Presumably this technique would be useful for other organoids (liver, kidney, etc.).

You can find the Cyfuse website here.

Autodesk in the tissue printing business

I came across the information about Autodesk’s venture into tissue printing in a Dec. 19, 2012 article by Kelsey Campbell-Dollaghan for Fast Company Co.Design.com (Note: Links have been removed),

Bioprinters–or 3-D printing hybrids that can print human tissue–have been around for a few years now. As the technology emerged, a single nagging question stuck out in the mind of this post-architecture school student: what’s the software of choice for a scientist modeling a human organ?

Today, an announcement from biomedical startup Organovo and software giant Autodesk goes a long way towards answering it. …

The Organovo Dec. 18, 2012 press release provides some detail about the deal,

Organovo Holdings, Inc. (OTCQX: ONVO) (“Organovo”), a creator and manufacturer of functional, three-dimensional human tissues for medical research and therapeutic applications, is working together with researchers at Autodesk, Inc., the leader in cloud-based design and engineering software, to create the first 3D design software for bioprinting.

The software, which will be used to control Organovo’s NovoGen MMX bioprinter, will represent a major step forward in usability and functionality for designing three-dimensional human tissues, and has the potential to open up bioprinting to a broader group of users.

This looks like it’s going to be a proprietary system, i.e., the software is designed for one type of hardware, Organovo’s hardware, reminiscent of the  late 1990s where printers in the graphic arts field were, in some cases, were trapped into proprietary computer-to-plate printing systems. There was an open source vs. proprietary systems competition which was eventually won by open source systems.

Organovo’s press release describes the technology they’ve developed,

Organovo’s 3D bioprinting technology is used to create living human tissues that are three-dimensional, architecturally correct, and made entirely of living human cells. The resulting structures can function like native human tissues, and represent an opportunity for advancement in medical research, drug discovery and development, and in the future, surgical therapies and transplantation.

The Dec. 17, 2012 article by Kim-Mai Cutler for TechCrunch adds more technical and business detail (Note: Link removed.),

Organovo, which went public earlier this year through a small cap offering and has a market cap of $98 million, manufactures a bioprinter that can create 1 millimeter-thick tissues. Based on research out of the University of Missouri, the company’s technology creates a bio-ink from cells and deposits new cells in a layer-by-layer matrix according to a computer design.

The Dec. 18, 2012 article by Joseph Flaherty for Wired magazine offers an analysis of the business advantages for both companies (Note: Links removed.),

Autodesk, the industry leader in CAD software, has announced it is partnering with biological printer manufacturer Organovo to create 3-D design software for designing and printing living tissue.

It’s an area of interest to Autodesk, whose software runs the industrial design and architecture worlds, allowing them to expand further into new fields by helping researchers interface with new tools.

“Autodesk is an excellent fit for developing new software for 3D bioprinters,” Organovo CEO Keith Murphy says in a press release. “This partnership will lead to advances in bioprinting, including both greater flexibility and throughput internally, and the potential long-term ability for customers to design their own 3D tissues for production by Organovo.”Jeff Kowalski, senior VP/CTO at Autodesk, echoes Murphy’s sentiment. “Bioprinting has the potential to change the world,” he says. “It’s a blend of engineering, biology and 3D printing, which makes it a natural for Autodesk. I think working with Organovo to explore and evolve this emerging field will yield some fascinating and radical advances in medical research.”

While this announcement is certainly big news, we’re multiple revisions away from 3-D printing replacement body parts. Even after the technical difficulties of printing organs or even tissue for live human use are worked through, any resulting process will need to be validated through complex clinical trials and a long review by the FDA and international authorities. Still, it will be exciting to see what medical researchers and DIY biohackers will do with these tools.

Oddly, as of today (Dec. 26, 2012) Autodesk has yet to post a press release about this deal on its own website.

Printing new knee cartilage

I was reminded of the 1992 Olympics in Barcelona while reading the Nov. 22, 2012 news item on Nanowerk about printing cartilage for knees. Some years ago I knew a Canadian wrestler who’d participated in those games and he had a story about knee cartilage that featured amputation.

Apparently, wrestlers in earlier generations had knee surgeries that involved removal of cartilage for therapeutic purposes. Unfortunately, decades later, these retired wrestlers found that whatever cartilage had remained was now worn through and bones were grinding on bones causing such pain that more than one wrestler agreed to amputation. I never did check out the story but it rang true largely because I’d come across a similar story from a physiotherapist regarding  a shoulder joint and the consequences of losing cartilage in there (very, very painful).

It seems that scientists are now working on a solution for those of us unlucky enough to have damaged or worn through cartilage in our joints, from the Nov. 22, 2012 IOP science news release, (Institute of Physics) which originated the news item,

The printing of 3D tissue has taken a major step forward with the creation of a novel hybrid printer that simplifies the process of creating implantable cartilage.


The printer is a combination of two low-cost fabrication techniques: a traditional ink jet printer and an electrospinning machine. Combining these systems allowed the scientists to build a structure made from natural and synthetic materials. …

In this study, the hybrid system produced cartilage constructs with increased mechanical stability compared to those created by an ink jet printer using gel material alone. The constructs were also shown to maintain their functional characteristics in the laboratory and a real-life system.

The key to this was the use of the electrospinning machine, which uses an electrical current to generate very fine fibres from a polymer solution. Electrospinning allows the composition of polymers to be easily controlled and therefore produces porous structures that encourage cells to integrate into surrounding tissue.

In this study, flexible mats of electrospun synthetic polymer were combined, layer-by-layer, with a solution of cartilage cells from a rabbit ear that were deposited using the traditional ink jet printer. The constructs were square with a 10cm diagonal and a 0.4mm thickness.

The researchers tested their strength by loading them with variable weights and, after one week, tested to see if the cartilage cells were still alive.

The constructs were also inserted into mice for two, four and eight weeks to see how they performed in a real life system. After eight weeks of implantation, the constructs appeared to have developed the structures and properties that are typical of elastic cartilage, demonstrating their potential for insertion into a patient.

The researchers state that in a future scenario, cartilage constructs could be clinically applied by using an MRI scan of a body part, such as the knee, as a blueprint for creating a matching construct. A careful selection of scaffold material for each patient’s construct would allow the implant to withstand mechanical forces while encouraging new cartilage to organise and fill the defect.

The researchers’ article in the IOP science jouBiofrarnal, Biofabrication, is freely available for 30 days after its date of publication, Nov. 21, 2012. You do need to register with IOP science to gain access. Here’s the citation and a link,

Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications by Tao Xu, Kyle W Binder, Mohammad Z Albanna, Dennis Dice, Weixin Zhao, James J Yoo and Anthony Atala in 2013 Biofabrication 5 015001 doi:10.1088/1758-5082/5/1/015001

I believe all of the scientists involved in this bioprinting project are with the Wake Forest Institute for Regenerative Medicine.

A new bio-ink, inkjet printers, and printing human cells at Australia’s University of Wollongong

Sometimes I look at my printer and just shake my head at the thought that one day it might produce living cells if the researchers at University of  Wollongong (New South Wales, Australia) have their way. From the Nov. 16, 2012 news item on phys.org,

Researchers have been aware for some time of the potential for using commercially available inkjet printer heads to print living human cells into 3D structures, but design of the actual ink capable of carrying cells through the printer has been a challenge.

The ARC Centre of Excellence for Electromaterials Science at UOW has led a team of scientists including Cameron Ferris, Dr Kerry Gilmore, Dr Stephen Beirne, Dr Donald McCallum, Professor Gordon Wallace and Associate Professor Marc in het Panhuis to develop a new bio-ink that improves the viability of living cells and allows better control of cell positioning through the printing process.

“To date, none of the available inks has been optimised in terms of both printability and cell suspending ability,” according to ACES Associate Researcher Cameron Ferris.

“Our new bio-ink is printable and cell-friendly, preventing cell settling and allowing controlled deposition of cells.”

The Nov. 15, 2012 University of Wollogong news release, which originated the news item, provides some detail about what makes this new bio-ink exciting,

The 2D structures being printed with the bio-ink enables exquisite control over cell distribution and this already presents exciting opportunities to improve drug screening and toxicology testing processes. Building on this, 3D bio-printing, with which patient-specific tissue replacements could be fabricated, is within the grasp of researchers.

The abstract for the researchers’ paper in Biomaterials helped me to build my understanding of this innovation,

Drop-on-demand bioprinting allows the controlled placement of living cells, and will benefit research in the fields of tissue engineering, drug screening and toxicology. We show that a bio-ink based on a novel microgel suspension in a surfactant-containing tissue culture medium can be used to reproducibly print several different cell types, from two different commercially available drop-on-demand printing systems, over long printing periods. The bio-ink maintains a stable cell suspension, preventing the settling and aggregation of cells that usually impedes cell printing, whilst meeting the stringent fluid property requirements needed to enable printing even from many-nozzle commercial inkjet print heads. This innovation in printing technology may pave the way for the biofabrication of multi-cellular structures and functional tissue.

You can access the paper (free access) but you must be registered (it’s free) with RSC (Royal Society of Chemistry) Publishing. Here’s a link and the citation,

Bio-ink for on-demand printing of living cells

Cameron J. Ferris ,  Kerry J. Gilmore ,  Stephen Beirne ,  Donald McCallum ,  Gordon G. Wallace and Marc in het Panhuis

Biomater. Sci., 2013, Advance Article

DOI: 10.1039/C2BM00114D
Received 09 Aug 2012, Accepted 11 Oct 2012
First published on the web 05 Nov 2012

Even more helpful than the abstract and assuming you’re not ready to read the paper is Jennifer Newton’s Nov. 7, 2012 article for the RSC’s Chemistry World,

‘The first bio-inks used in drop-on-demand cell printing were simple salt solutions,’ says Marc in het Panhuis, who was part of the research team at the University of Wollongong. ‘The cells in these inks settled and aggregated quickly, which impeded printing. Cell viability can also be compromised if the salt concentration is too high.’

Other bio-inks include low viscosity biopolymer solutions, which are known to slow cell settling. The team’s bio-ink consists of a biopolymer – gellan gum – and two surfactants in a standard tissue culture medium. The surfactants – Novec FC4430 and Poloxamer 188 – reduce surface tension, allowing optimal inkjet printing, and protect the cells from fluid-mechanical damage.

The cells do not settle and aggregate because the biopolymer creates a structured network of micro-gel particles that keep the cells suspended in the gel. However, the bio-ink remains printable as the network is not rigid and is easily broken down during printing. ‘Our bio-ink allowed us to print multiple cell types over long printing periods without changing print heads or replenishing ink solutions,’ says in het Panhuis.

There are more details in Newton’s article and the image that accompanies it is quite striking.