SC9: Challenges of Moving from Bench to Bedside in Tissue Engineering

Written by: Roshni Rainbow, PhD (Clerk), Nathan Holwell (Chair), and Laura McKiel (Editor)

A typical process of moving from bench to bedside includes developing a material and performing in vitro testing, followed by in vivo testing in animals, and finally human trials. In vitro analysis begins to test the biocompatibility of the material using cells outside the body. Animal models are used for in vivo testing to take a more detailed look at the biocompatibility within a living subject. Researchers usually explore the material’s role in tissue viability, inflammation, cellular infiltration, and fibrotic response. Finally, human trials explore the feasibility of the material for the intended application supported by clinical trials.

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Figure 1: The typical process for drug development, testing, and approval. Source: http://oirm.ca/sites/default/files/oirm-infographic-nov2016-final.pdf

In the first breakout session, we explores the next steps of  two different biomedical technologies in order to move them into a clinical application.

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A major challenge of clinical trials is to appropriately scale-up the manufacturing process. A significant factor in scale-up is the propagation of cells and automating device production. As an example, microencapsulated pancreatic islets for diabetes treatment needs 500 islets for a 100 g mouse. To scale up to a 20 kg dog, 1,000,000 islets would be needed. Due to diffusion limitations, implanted capsules cannot be larger than ~200 µm in one direction. For a 100 g mouse, 1 microcapsule is required, but for a 20 kg dog one would need a 15 foot long string.

For clinical trials to begin, there are a few conditions that must be met. Firstly, the trial benefit must outweigh the risk. Secondly, the researchers must obtain free and informed consent from the patients involved in the trial. Finally, the protocol must be reviewed in advance by an independent review board. With this knowledge in mind, another example of a clinical trial was explored.

The Hepatassist Circuit Therapy by Circe Biomedical Inc. was a device to provide bioartificial liver support. When they performed their clinical trials, they had a total patient size of 116. However, 85 of these patients were part of the control portion of the study. This demonstrates the need to fully consider the number patients being studied with the actual device. The study population is especially important to consider when determining whether the material in questions has a true effect or not. And if the device does not show an effect, it is possible that it either doesn’t work or wasn’t tested in enough patients to show its true effect.

Next, we discussed the limited success of tissue engineering companies or firms. It was agreed that these companies or firms are good at discovery but lack in product development and regulatory medicine. Tissue engineered products are generally required to follow phase I/II/III regulatory pathways for pharmaceutical compounds. These submissions can cost anywhere from 300-500 million dollars. Tissue engineered products are usually discovered by smaller companies with limited funds. Due to this funds limitation, they cannot afford submission and must rely on investors. If trials are performed, they are usually done in a cheap manner. Unfortunately, these trials typically fail or only provide a narrow indication as to the material’s effect.

At the end of the session, we discussed a recent paper that commented on the greatest regulatory challenges in the translation of biomaterials to the clinic.

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This article tackles the issue of clinical translation of biomaterials from a variety of viewpoints. Lawyers, regulatory officials, clinicians, and researchers comment on what they perceive to be the most difficult challenge of translating biomaterials from the bench to the clinic.

Among the arguments raised in this article by the various viewpoints, one question loomed at the end: Should scientists innovate or translate?

33rd Annual Meeting of the Canadian Biomaterials Society: Winnipeg, MB

33rd Annual Meeting of the Canadian Biomaterials Society: Winnipeg, MB

Last week we had the pleasure of attending the 33rd Annual Meeting of the Canadian Biomaterials Society, which was held in Winnipeg, MB May 24-27. In addition to our own personal research presentations, CBS-KSC presented a poster on our first Science Club during the poster session. We had a great time networking with the other student chapters and have some great ideas for student events during the upcoming year. Can’t wait for the CBS meeting next year in Victoria, BC!

Congratulations to all of our students who presented!

  • Amanda Brissenden (PhD student, Amsden lab, oral) – Development of a Thermoresponsive Homopolymer for Biomedical Applications
  • William Chaplin (MASc candidate, Fitzpatrick lab, oral) – Development of a Zebrafish-based Platform for Evaluating the Inflammatory Response to Implanted Biomaterials
  • Ashley Clarke (MASc candidate, Wells lab, poster) – Modification of Poly(methyl methacrylate) Surfaces with Azobenzene Groups as a Photoswitchable Surface
  • Christina Ippolito (MASc candidate, Bryant lab, oral) –  The effects of fluid viscosity on stress shielding in uniformly textured UHMWPE during the dwell phase of SDS motion
  • Laura McKiel (PhD candidate, Fitzpatrick lab, oral) – Toll-like Receptor 2-mediated NF-kB Activation by Damage-associated Molecular Patterns on Biomaterial Surfaces
  • Gad Sabbatier, PhD (Postdoctoral fellow, Amsden lab, oral) – Dynamic Stimulation of Alginate-Based Hydrogels to Differentiate Adipose-Derived Stem Cells Towards Nucleus Pulposus Cells

You can check out our Science Club poster, showing the highlights from our session on Frontiers in Biomaterials and Tissue Engineering HERE!

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Summary: Eastern Ontario CBS Symposium 2017

Summary: Eastern Ontario CBS Symposium 2017

The first annual Eastern Ontario CBS symposium, held on May 19th in the Human Mobility Research Centre of Kingston General Hospital, was a HUGE success! Students who were presenting at the 33rd Annual General Meeting of the Canadian Biomaterials Society were able to practice their presentations and receive valuable feedback from their peers. A very special highlight from the event was an outstanding keynote presentation given by Dr. Isabelle Catelas from the University of Ottawa. We were very excited to also have some members from the CBS Ottawa Student Chapter (CBS-OSC) join us at this event, and can’t wait to collaborate on more events in the future!

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Our attendees included undergraduate and graduate students, postdoctoral fellows, principal investigators from a wide variety of departments, including chemical engineering, mechanical engineering, electrical engineering, computer science, and biomedical science, from both Queen’s University and the University of Ottawa. We even had HMRC employees stop in to check out the poster session!

We would like to congratulate our winners for Best Presentation: William Chaplin (oral) and Srijit Nair (poster). Looking forward to making the event even better next year!

You can refer to the Symposium Booklet and Program (below) for more details on the event.

EO-CBS Program

 

SC8: Tissue engineering beyond medical applications… What’s next?

Written by Gad Sabbatier, Ph.D (Chair), Ashley Clarke (Clerk), and Laura McKiel (Editor)

Tissue engineering principles were defined in 1993 by Langer and Vacanti with a great promise to produce laboratory-made organs, regenerate organs, or repair an organ function for everybody. In 2017, technologies developed with tissue engineering and regenerative medicine principles cure a small number of patients compared to the demand. Due to a long (and largely undefined) regulatory process and revamping standards to fit with this new market, companies work for decades between the proof of concept and the commercialization of a tissue engineered medical devices and spend millions of dollars of investments. In the meantime, academic scientists have gained a lot of expertise and knowledge towards refining this learning process and developing a wide range of principles, techniques, methods, materials, proof of concepts and possible applications in tissue engineering and regenerative medicine.

During this session, we imagined ourselves in a start up company trying to commercialize a tissue engineered product, developing short term products and considering the expertise required to finance longer-term products. Two focus questions included:

  • What else we can do with tissue engineering principles to avoid or decrease time of regulatory pathway?
  • What’s coming next to tissue engineering?

 

How tissue engineering and regenerative medicine can help the food industry

Cultured meat is the most popular example in the media for the past few years. It consists of highly proliferative progenitor cells that differentiate into myocytes. The first cultured beef burger was produced by Dr. Mark Post group from Maastricht University and eaten in London in 2013. Many start-up companies have since started to culture fish, chicken meat, duck or pork meat. Of course, cultured meat needs optimization and scale-up to decrease the cost, but is estimated to be commercialized in a decade at a reasonable price. Lab-grown meat solves many agricultural issues such as the large greenhouse gas emissions of farming and water needed for livestock. This application will potentially require lighter regulation processes compared to tissue engineered medical products, but to date this still remains unclear. Read more about this topic here.

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Figure 1: An overview of the process of making tissue engineered meat. Source: Z. F. Bhat and H. Bhat. Journal of Stored Products and Postharvest Research, 2011, vol. 2, no. 1, pp. 1 – 10.

 

 

How tissue engineering and regenerative medicine can be used in the fashion and sports industries

Several researchers are trying to push the boundaries of the fashion industry by producing ivory, leather, silk, or fur using tissue engineering principles. These techniques can be employed to make ethical jewelry or luxury clothes that do not need to kill animals. Another project based on protocell technology envisions self-repairing personalized shoes that can react to pressure, heat, and topography (Figure 2).

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Figure 2: Concept of protocell shoes. Source: https://www.dezeen.com/2014/02/19/movie-shamees-aden-protocells-regenerating-trainers/

 

How tissue engineering and regenerative medicine can be applied to robotics

Many scientists are interested in bridging the gap between humans and robots by building bio-bots from living human tissues. Engineers from the University of Illinois made a walking robot with skeletal muscle cells on a 3D printed polymeric matrix that can be stimulated electrically to move (Figure 3).

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Figure 3: The walking bio-bot. Source: http://engineering.illinois.edu/do-the-impossible/biobots/

During the science club, we discussed the problem of fabricating a vascularized artificial skin for robots. Living skin on a robot would require the presence of blood vessels and artificial blood (blood/ biofluid supply system) with oxygen and nutrients, in addition to finding a means to distribute stem cells to replace apoptotic skin or blood cells. We also thought about a way to stimulate skin growing on orthopedics or exoskeletons by grafting peptides onto metal, to promote migration and adhesion of epithelial cells.

 

How tissue engineering and regenerative medicine can help the aerospace industry

Finally, we discussed how organs may evolve on Mars. Recently, NASA performed study to understand DNA changes due to durations in space. The DNA of twin astronauts Scott and Mark Kelly were compared after one brother had been in the International Space Station (ISS) for one year while the other stayed on earth. After the trip to space, the twins no longer had identical genetic code, proving that the environment in the ISS affects DNA. We imagined a series of experiments to study the development of organs in space or on Mars using stem or mature cells in a bioreactor that reproduces the Mars environmental conditions. Also, we wondered how non-Earth environments will affect the bodies and genetics of future generations of humans after colonization

SC7: The ethics of using stem cells in tissue engineering

Written by Gad Sabbatier (Clerk), Hossein Riahinezhad (Chair), and Laura McKiel (Editor)

Two weeks ago, we watched a documentary “Supercells: from stem cells to artificial organ” about trachea transplantation to illustrate the topic of our weekly science club.

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The documentary was about a young Russian woman, Yulia Tuulik, a former dancer with the bolshoï ballet, who needed a tracheotomy because of a car accident in 2011. A multidisciplinary team of surgeons, scientists, and industrialists lead by Paolo Macchiarini, a world known surgeon, implanted a bioengineered synthetic nanofibrous trachea seeded with bone-marrow derived stem cells prior harvested on the patient. Cells were seeded on the scaffold using a rotational bioreactor for 48 hours, and then suspended and observed every two hours in aseptic conditions. The patient underwent this “first-in-man” transplantation surgery on June 2012 at Krasnodarsk in Russia. The documentary has shown how this surgery was publicized by the media, and the success of the surgery after implantation.

Yulia Tuulik unfortunately died on September 2014 because of chronic inflammation, chronic coughs, and choking; Paolo Miccharini was found guilty for misconduct in 2015. This documentary is impressive, very well explained, and continues to be very popular on the web (4.5 stars on Amazon – outstanding comments in 2017), but fails to explain the death of the patient.

At the end of the movie, we discussed the limitations of the documentary. In the following, there is a summary of our discussion.

  • Everyone agrees that the relationship between doctors and the patient was constructive. It was shown in the movie that team of doctors visited Yulia on a regular basis before surgery and Mr. Green, CEO of Harvard Bioscience (who designed the bioreactor for cell seeding on synthetic trachea), showed the bioreactor to the patient and explained the basic science of what they want to do. Jed Johnson, CTO of Nanofibers Solutions and material designer of the synthetic trachea, was not involved in the surgery.
  • We also discussed about differences between scientists and surgeons, and the need to teach surgeons how to work with biomaterials that are produced by scientists. Based on part of the movie, Dr. Macchiarini tested the stiffness of the synthetic trachea by putting a bottle on top of it and checking how easy it was to handle and suture. On the other hand, scientists are more careful and design different experiments to measure mechanical properties of an implant. We are wondering if scientists should design materials which completely fulfill the surgeon’s expectations, or surgeons should be properly trained to use that material. We agree that it is necessary to train surgeons regarding handling of the material, storage, and some of the characteristics of the material that could lead to improvement of the surgery and patient outcomes.
  • Since the surgery was done in Russia, the regulatory process that authorize the surgery using this synthetic trachea seeded with stem cells and transplant it on human might have been different from the United States (FDA) or the European Union.
  • The patient was young (34 years-old) and in very good physical health (dancer), which played a key role into the choice of the patient for a successful first-in-man surgery.

Overall, this procedure showed that tissue engineered trachea transplantation may be premature and need more investigation.