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Perpetual patterns

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May/June 2013 Volume Volume 6 Issue Issue 3

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By William Leventon

Contributing Editor

(609) 926-6447

wleventon@verizon.net

Nanopatterned medical implants may last a lifetime

Nanopatterns on orthopedic implants may one day lengthen the service lives of those implants, slashing the number of replacement surgeries needed due to implant failures and improving the lives of millions of people with artificial joints.

Consider hip implants, which are held in place by a rod placed inside the bone marrow. Mesenchymal stem cells in the marrow can transform, or differentiate, into bone cells that improve the healing process by strengthening the bond, or integration, between the implant and the surrounding bone. However, these cells typically differentiate into soft tissue that can weaken the implant/body bond.

As the bond deteriorates, or loosens, the life span of an implant decreases. Implants typically must be replaced after 15 or 20 years. With people living longer, and with more implants going into younger patients, more secondary surgeries must be done to replace the original implants.

A solution you can’t see

What can be done to prevent problematic implant loosening? The answer may be to modify implant surfaces with patterns consisting of features so small that they can’t be seen even with optical microscopes. In previous research, scientists discovered that cells are responsive to the height, depth, spacing and arrangement of such features.

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A nanopatterned PEEK sample (top). Above: The nanopatterned PEEK substrate. Image courtesy University of Glasgow.

In the U.K., two groups of researchers are exploring the effects nanoscale surface patterns have on cell behavior around implants. Their work suggests that certain nano-patterns encourage stem cells to differentiate into bone cells, which would improve the integration of implants with surrounding bone. This could mean that nanopatterned implants would last in the body as long as patients lived, eliminating the need for follow-up replacement surgeries.

At the University of Bristol, a research team is nanopatterning titanium, a commonly used biocompatible material that bonds well with bone. The patterns used by the Bristol team consist of arrays of “nanopillars.” In-vitro studies show that stem cell behavior depends, in part, on the height of these tiny pillars, according to Terje Sjöström, a member of the Bristol team. Sjöström points to studies by his team showing that stem cells inserted on 15nm-high pillars are more likely to differentiate into bone cells than will stem cells on a flat surface. This behavior becomes increasingly less likely as pillar height increases.

According to Sjöström, other research groups have shown that spacing between features on a nanopatterned surface is also crucial to how cells behave on that surface. For example, the research shows that cells struggle to adhere to and function on surfaces with features spaced more than 70nm apart, he said. Therefore, the Bristol team tries to keep the spacing of its surface features below the 70nm threshold.

Building pillar patterns

To create its pillar patterns, the team uses through-mask anodic oxidation, or anodization, an electrochemical process commonly used to grow titanium oxide on titanium surfaces. In one process, a titanium surface is covered with a thin film of aluminum, which is anodized to form a nanoporous aluminum-oxide mask on the titanium. Then, the titanium is anodized through the nanoporous mask, causing titanium-oxide pillars to grow in the pores of the mask. In the final step, the mask is etched away, leaving only the pillar pattern.

Another process used by the Bristol team involves anodizing a titanium substrate through a block copolymer (BCP) template. A BCP mask is more easily created on a complex, 3-D titanium surface than is an aluminum-oxide mask, making the process more suitable for commercial fabrication, according to Sjöström.

On a titanium surface, a thin BCP film self-organizes into a template with an array of tiny openings in which nanopillars are formed during anodization. When the template is removed, what’s left is an oxide nanopattern on the titanium surface. Sjöström said his team has shown that this technique can be used to create titanium-oxide patterns consisting of 15nm-high pillars.

In addition to flat surfaces, the University of Bristol team used its anodization techniques to pattern rod surfaces, as well as micro-bead surfaces (consisting of tiny spherical titanium beads) like those used on some implants. So far, the work has been limited to in-vitro research, Sjöström noted. Animal testing is the next step to attempt to prove that the patterned surfaces work as expected in living creatures.

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This image shows 100nm-high titaninium-oxide nanopillars on a titanium substrate created via through-mask anodic oxidation. Image courtesy University of Bristol.

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This image shows 15nm-high titanium-oxide nanodots on a titanium substrate created by anodizing the substrate through a block copolymer (BCP) template. Image courtesy University of Bristol.

Polymer possibilities

In Scotland, meanwhile, scientists at the University of Glasgow are working with surgeons at Glasgow’s Southern General Hospital on nanopatterns that encourage bone-cell growth on an implantable thermoplastic polymer known as PEEK-OPTIMA, a common choice for a number of orthopedic procedures.

One reason polyether-ether ketone is a better material choice than titanium is that it has flex characteristics similar to that of bone, according to the researchers. Titanium is inflexible. Therefore, titanium implants prevent the supported bone from being strengthened by normal exercise, causing the bone to weaken. Implants made of PEEK can flex in a natural manner and give a boost to the bone-regeneration process, explained Nikolaj Gadegaard, a biomedical engineer on the Glasgow team.

PEEK is also strong, stable and doesn’t block X-rays. In addition, Gadegaard said, it’s a highly wear-resistant material, so when PEEK implant components rub against each other, they are less likely to shed particles or pieces in the body than are implants made of metal or other plastics.

On the downside, PEEK is inert, which means it is accepted by the body but doesn’t form a tight bond with bone. Faced with this problem, Gadegaard and his colleagues have come up with surface patterns that may cause normally inert PEEK to interact with stem cells to effectively integrate implants made of the material with bone. The patterns are arrays of “pits” 100nm deep and 100nm to 120nm in diameter. Initially, the Glasgow researchers spaced holes exactly 300nm apart, but they discovered that bone cell differentiation benefits from a little “disorder” in the pattern, Gadegaard said. Each hole is now randomly displaced by up to 50nm, meaning that the spacing won’t be exactly 300nm but will be up to 50nm more or less than 300nm.

Another plus for PEEK is that it can be injection-molded. This opens up the possibility of mass-produced nanopatterned PEEK implants, which could be considerably less expensive than individually machined titanium implants, Gadegaard noted.

Multistep process

With mass production in mind, Gadegaard and his colleagues have come up with a multistep process for producing nanopatterned PEEK parts. First, electron beam lithography (EBL) is used to create the nanopatterns. After a pattern is lithographically created on a master substrate, a “negative” of the pattern is transferred to a nickel shim about 0.33mm thick, which is produced by an electroplating process. This shim is then cut to fit into an injection-molding tool, where the tiny pillars on the shim’s surface produce the EBL-created pattern on molded PEEK parts.

“Though a large amount of effort goes into making the pattern, there’s no limit to the number of parts we can make once the pattern is in the mold,” Gadegaard said. “We’ve been running thousands of parts up against these nanopatterns on the shims, and we haven’t been able to detect any deterioration in the patterns.”

Because semiconductor-fabrication technology is used to make the master nanopattern substrates, the Glasgow team had to determine how to transfer the patterns on these flat substrates to 3-D implant surfaces. Gadegaard called the task “tricky,” but reported that his team has made the first prototypes, which shows that it can be done.

If nanopatterning of implant surfaces catches on, it could eventually lead to a future in which individual implants could include a number of different topographical “zones” designed to elicit different cell responses. For example, one zone could be patterned to encourage bone integration, another to promote attachment of tendons and still another to prevent any type of tissue growth.

Said Gadegaard: “I call it civil engineering on a nanoscale.” µ


Contributors

University of Glasgow
+44 141 330 200
www.gla.ac.uk

University of Bristol
+44 117 928 9000
www.bris.ac.uk

FtrAuthorAbout

William Leventon is a New Jersey-based freelance writer. He has a M.S. in Engineering from the University of Pennsylvania and a B.S. in Engineering from Temple University. Telephone: (609) 926-6447. E-mail: wleventon@verizon.net. Telephone: (609) 926-6447. E-mail:  wleventon@verizon.net.