Tag Archives: Kathryn Grandfield

Canadian researchers develop bone implant material from cellulose nanocrystals (CNC) while Russian scientists restore internal structure of bone with polycaprolactone nanofibers

Two research groups are working to the same end where bone marrow is concerned, encourage bone cell growth, but they are using different strategies.

University of British Columbia and McMaster University (Canada)

Caption: Researchers treated nanocrystals derived from plant cellulose so that they can link up and form a strong but lightweight sponge (an aerogel) that can compress or expand as needed to completely fill out a bone cavity. Credit: Clare Kiernan, UBC

The samples look a little like teeth, don’t they?

Before diving into the research news, there’s a terminology issue that should be noted as you’ll see when you read the news/press releases. Nanocrystal cellulose/nanocrystalline cellulose (NCC) is a term coined by Canadian researchers. Since those early day, most researchers, internationally, have adopted the term cellulose nanocrystals (CNC) as the standard term. It fits better with the naming conventions for other nnanocellulose materials such as cellulose nanofibrils, etc. By the way, a Canadian company (CelluForce) that produces CNC retained the term nanocrystalline cellulose (NCC) as a trademark for the product, CelluForce NCC®.

For anyone not familiar with aerogels, what the University of British Columbia (UBC) and McMaster University researchers are developing, are also popularly known known as ‘frozen smoke’ (see the Aerogel Wikipedia entry for more).

A March 19, 2019 news item on ScienceDaily announces the research,

Researchers from the University of British Columbia and McMaster University have developed what could be the bone implant material of the future: an airy, foamlike substance that can be injected into the body and provide scaffolding for the growth of new bone.

It’s made by treating nanocrystals derived from plant cellulose so that they link up and form a strong but lightweight sponge — technically speaking, an aerogel — that can compress or expand as needed to completely fill out a bone cavity.

A March 19, 2019 UBC news release (also on EurekAlert), which originated the news item, describes the research in more detail,

“Most bone graft or implants are made of hard, brittle ceramic that doesn’t always conform to the shape of the hole, and those gaps can lead to poor growth of the bone and implant failure,” said study author Daniel Osorio, a PhD student in chemical engineering at McMaster. “We created this cellulose nanocrystal aerogel as a more effective alternative to these synthetic materials.”

For their research, the team worked with two groups of rats, with the first group receiving the aerogel implants and the second group receiving none. Results showed that the group with implants saw 33 per cent more bone growth at the three-week mark and 50 per cent more bone growth at the 12-week mark, compared to the controls.

“These findings show, for the first time in a lab setting, that a cellulose nanocrystal aerogel can support new bone growth,” said study co-author Emily Cranston, a professor of wood science and chemical and biological engineering who holds the President’s Excellence Chair in Forest Bio-products at UBC. She added that the implant should break down into non-toxic components in the body as the bone starts to heal.

The innovation can potentially fill a niche in the $2-billion bone graft market in North America, said study co-author Kathryn Grandfield, a professor of materials science and engineering, and biomedical engineering at McMaster who supervised the work.

“We can see this aerogel being used for a number of applications including dental implants and spinal and joint replacement surgeries,” said Grandfield. “And it will be economical because the raw material, the nanocellulose, is already being produced in commercial quantities.”

The researchers say it will be some time before the aerogel makes it out of the lab and into the operating room.

“This summer, we will study the mechanisms between the bone and implant that lead to bone growth,” said Grandfield. “We’ll also look at how the implant degrades using advanced microscopes. After that, more biological testing will be required before it is ready for clinical trials.”

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

Cross-linked cellulose nanocrystal aerogels as viable bone tissue scaffolds by Daniel A. Osorio, Bryan E. J. Lee, Jacek M. Kwiecien, Xiaoyue Wang, Iflah Shahid, Ariana L. Hurley, Emily D. Cranston and Kathryn Grandfield. Acta Biomaterialia Volume 87, 15 March 2019, Pages 152-165 DOI: https://doi.org/10.1016/j.actbio.2019.01.049

This paper is behind a paywall

Now for the Russian team.

National University of Science and Technology “MISIS” (formerly part of the Moscow Mining Academy)

These scientists have adopted a different strategy as you’ll see in the March 19, 2019 news item on Nanwerk, which, coincidentally, was published on the same day as the Canadian research,

Scientists from the National University of Science and Technology “MISIS” developed a nanomaterial, which will be able to rstore the internal structure of bones damaged due to osteoporosis and osteomyelitis. A special bioactive coating of the material helped to increase the rate of division of bone cells by 3 times. In the future, it can allow to abandon bone marrow transplantation and patients will no longer need to wait for suitable donor material.

A March 19, 2019 National University of Science and Technology (MISIS) press release (also on EurekAlert), which originated the news item, provides detail about the impetus for the research and the technique being developed,

Such diseases as osteoporosis and osteomyelitis cause irreversible degenerative changes in the bone structure. Such diseases require serious complex treatment and surgery and transplantation of the destroyed bone marrow in severe stages. Donor material should have a number of compatibility indicators and even close relationship with the donor cannot guarantee full compatibility.

Research group from the National University of Science and Technology “MISIS” (NUST MISIS), led by Anton Manakhov (Laboratory for Inorganic Nanomaterials) developed material that will allow to restore damaged internal bone structure without bone marrow transplantation.
It is based on nanofibers of polycaprolactone, which is biocompatible self-dissolvable material. Earlier, the same research group has already worked with this material: by adding antibiotics to the nanofibers, scientists have managed to create non-changeable healing bandages.

“If we want the implant to take, not only biocompatibility is needed, but also activation of the natural cell growth on the surface of the material. Polycaprolactone as such is a hydrophobic material, meaning, and cells feel uncomfortable on its surface. They gather on the smooth surface and divide extremely slow”, Elizaveta Permyakova, one of the co-authors and researcher at NUST MISIS Laboratory for Inorganic Nanomaterials, explains.

To increase the hydrophilicity of the material, a thin layer of bioactive film consisting of titanium, calcium, phosphorus, carbon, oxygen and nitrogen (TiCaPCON) was deposited on it. The structure of nanofibers identical to the cell surface was preserved. These films, when immersed in a special salt medium, which chemical composition is identical to human blood plasma, are able to form on its surface a special layer of calcium and phosphorus, which in natural conditions forms the main part of the bone. Due to the chemical similarity and the structure of nanofibers, new bone tissue begins to grow rapidly on this layer. Most importantly, polycaprolactone nanofibers dissolve, having fulfilled their functions. Only new “native” tissue remains in the bone.

In the experimental part of the study, the researchers compared the rate of division of osteoblastic bone cells on the surface of the modified and unmodified material. It was found that the modified material TiCaPCON has a high hydrophilicity. In contrast to the unmodified material, the cells on its surface felt clearly more comfortable, and divided three times faster.

According to scientists, such results open up great prospects for further work with modified polycaprolactone nanofibers as an alternative to bone marrow transplantation.

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

Bioactive TiCaPCON-coated PCL nanofibers as a promising material for bone tissue engineering by Anton Manakhov, Elizaveta S. Permyakova, Sergey Ershov, Alexander Sheveyko, Andrey Kovalskii, Josef Polčák, Irina Y. Zhitnyak, Natalia A. Gloushankova, Lenka Zajíčková, Dmitry V. Shtansky. Applied Surface Science Volume 479, 15 June 2019, Pages 796-802 DOI: https://doi.org/10.1016/j.apsusc.2019.02.163

This paper is behind a paywall.

Lighting the way to improvements for the bond between dental implants and bone

A July 3, 2018 Canadian Light Source news release by Colleen MacPherson describes an investigation into how dental implants and bones interact with the hope of making dental implantation safer and more certain,

Research carried out recently at the Canadian Light Source (CLS) [also known as a synchrotron] in Saskatoon [Saskatchewan, Canada] has revealed promising information about how to build a better dental implant, one that integrates more readily with bone to reduce the risk of failure.

“There are millions of dental and orthopedic implants placed every year in North America and a certain number of them always fail, even in healthy people with healthy bone,” said Kathryn Grandfield, assistant professor in the Department of Materials Science and Engineering at McMaster University in Hamilton [Ontario, Canada].

A dental implant restores function after a tooth is lost or removed. It is usually a screw shaped implant that is placed in the jaw bone and acts as the tooth roots, while an artificial tooth is placed on top. The implant portion is the artificial root that holds an artificial tooth in place.

Grandfield led a study that showed altering the surface of a titanium implant improved its connection to the surrounding bone. It is a finding that may well be applicable to other kinds of metal implants, including engineered knees and hips, and even plates used to secure bone fractures.

About three million people in North America receive dental implants annually. While the failure rate is only one to two percent, “one or two percent of three million is a lot,” she said. Orthopedic implants fail up to five per cent of the time within the first 10 years; the expected life of these devices is about 20 to 25 years, she added.

“What we’re trying to discover is why they fail, and why the implants that are successful work. Our goal is to understand the bone-implant interface in order to improve the design of implants.”

Grandfield’s research team, which included post-doctoral fellow Xiaoyue Wang and McMaster colleague Adam Hitchcock from the Department of Chemistry and Chemical Biology. The team members used the soft X-ray spectromicroscopy beamline at the CLS as well as facilities at the Canadian Centre for Electron Microscopy in Hamilton to examine a failed dental implant that had to be removed, along with a small amount of surrounding bone, from a patient. Prior to implantation, a laser beam was used to alter the implant, to roughen the surface, creating what looked like “little volcanoes” on the surface. After removal from the patient, the point of connection between bone and metal was then carefully studied to understand how the implant behaved.

“What we found was that the surface modification changed the chemistry of the implant. The modification created an oxide layer, but not a bad oxide layer like rust but a better, more beneficial layer that helps integrate with bone material.”

The research results were published in Advanced Materials Interfaces in May [2018], ensuring the findings are available “to implant companies interested in using nanotechnology to change the structure of the implants they produce,” said Grandfield.

The next steps in the research will be to apply the surface modification technique to other types of implants “to be able to understand fully how they function.” Grandfield added the research done at the CLS involved healthy bone “so I’d be really interested in seeing the response when bone is a bit more compromised by age or disease, like osteoporosis. We need to find the best surface modifications … because the technology we have today to treat patients with healthier bone may not be sufficient with compromised bone.”

Here’s a link to (even though it’s in the news release text) and a citation for the paper,

Biomineralization at Titanium Revealed by Correlative 4D Tomographic and Spectroscopic Methods by Xiaoyue Wang, Brian Langelier, Furqan A. Shah, Andreas Korinek, Matthieu Bugnet, Adam P. Hitchcock, Anders Palmquist, Kathryn Grandfield. Advnaced Materials Interfaces https://doi-org.proxy.lib.sfu.ca/10.1002/admi.201800262 First published: 16 May 2018

This paper is behind a paywall.

Upsalite, an impossible material from Uppsala University (Sweden) and Disruptive Materials

You can feel the researchers’ excitement crackling from the July 18, 2013 news release (English language version available at Uppsala University [Sweden]) about a new material that shares properties with zeolite, mesoporous silica, and carbon nanotubes and has some special properties all its own,

A novel material with world record breaking surface area and water adsorption abilities has been synthesized by researchers from Uppsala University, Sweden. The results are published today in PLOS ONE.

The magnesium carbonate material that has been given the name Upsalite is foreseen to reduce the amount of energy needed to control environmental moisture in the electronics and drug formulation industry as well as in hockey rinks and warehouses. It can also be used for collection of toxic waste, chemicals or oil spill and in drug delivery systems, for odor control and sanitation after fire.

Apparently this work represents a break with orthodoxy, from the news release,

-In contrast to what has been claimed for more than 100 years in the scientific literature, we have found that amorphous magnesium carbonate can be made in a very simple, low-temperature process, says Johan Forsgren, researcher at the Nanotechnology and Functional Materials Division

While ordered forms of magnesium carbonate, both with and without water in the structure, are abundant in nature, water-free disordered forms have been proven extremely difficult to make. In 1908, German researchers claimed that the material could indeed not be made in the same way as other disordered carbonates, by bubbling CO2 through an alcoholic suspension. Subsequent studies in 1926 and 1961 came to the same conclusion.

-A Thursday afternoon in 2011, we slightly changed the synthesis parameters of the earlier employed unsuccessful attempts, and by mistake left the material in the reaction chamber over the weekend. Back at work on Monday morning we discovered that a rigid gel had formed and after drying this gel we started to get excited, says Johan Forsgren.

A year of detailed materials analysis and fine tuning of the experiment followed.

-One of the researchers got to take advantage of his Russian skill since some of the chemistry details necessary for understanding the reaction mechanism was only available in an old Russian PhD thesis.

-After having gone through a number of state of the art materials characterization techniques it became clear that we had indeed synthesized the material that previously had been claimed impossible to make, says Maria Strømme, professor of nanotechnology and head of the nanotechnology and functional materials division. The most striking discovery was, however, not that we had produced a new material but it was instead the striking properties we found that this novel material possessed. It turned out that Upsalite had the highest surface area measured for an alkali earth metal carbonate; 800 square meters per gram. This places the new material in the exclusive class of porous, high surface area materials including mesoporous silica, zeolites, metal organic frameworks, and carbon nanotubes, says Strømme.

In addition we found that the material was filled with empty pores all having a diameter smaller than 10 nano meters. This pore structure gives the material a totally unique way of interacting with the environment leading to a number of properties important for application of the material. Upsalite is for example found to absorb more water at low relative humidities than the best materials presently available; the hydroscopic zeolites, a property that can be regenerated with less energy consumption than is used in similar processes today.

This, together with other unique properties of the discovered impossible material is expected to pave the way for new sustainable products in a number of industrial applications, says Maria Strømme.

The discovery will be commercialized though the University spin-out company Disruptive Materials (www.disruptivematerials.com) that has been formed by the researchers together with the holding company of Uppsala University

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

A Template-Free, Ultra-Adsorbing, High Surface Area Carbonate Nanostructure by Johan Forsgren, Sara Frykstrand, Kathryn Grandfield, Albert Mihranyan, and Maria Strømme. PLoS ONE, 2013; 8 (7): e68486 DOI: 10.1371/journal.pone.0068486

Here’s a little more abut Upsalite from the university’s spin-off company, Disruptive Materials homepage,

 Upsalite
A new material with world record breaking surface area and water adsorption abilities

It was supposed to be impossible, but… We did it! Disruptive Materials has succeeded to manufacture micro-porous magnesium carbonate and the properties are mind blowing. Over 800 m2/g in surface area, better water adsorbtion ability than the former champion Zeolite Y and a very low manufacturing cost. We have been testing the material for a long time, and we see new applications every week for this new and true super-material.

Finally for those with Swedish language skills, here’s the July 18, 2013 news release from Disruptive Materials.