Tag Archives: joint replacements

Apatite nanoparticles advance biocompatibility of implanted biodevices

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Should you ever need need or already have a joint (knee, hip, etc.) replacement, an implant (brain, pacemeker, etc.) or other biomedical device in your body, this work from Japan is likely to be of special interest.

Caption: Researchers from Nagaoka University of Technology, Japan develop highly biocompatible apatite nanoparticles by manipulating surface properties through pH changes. Credit: Motohiro Tagaya from Nagaoka University of Technology, Japan

Before moving onto the press release, bravo to whoever wrote it! Thank you for clear, thoughtful explanations. Here’s the January 30, 2025 Nagaoka University of Technology press release (also on EurekAlert but published on February 4, 2025), Note: A link has been removed,

Medical implants have transformed healthcare, offering innovative solutions with advanced materials and technologies. However, many biomedical devices face challenges like insufficient cell adhesion, leading to inflammatory responses after their implantation in the body. Apatite coatings, particularly hydroxyapatite (HA)—a naturally occurring form of apatite found in bones, have been shown to promote better integration with surrounding tissues. However, the biocompatibility of artificially synthesized apatite nanoparticles often falls short of expectations, primarily due to the nanoparticles’ limited ability to bind effectively with biological tissues.

To overcome this challenge, researchers at Nagaoka University of Technology, Japan have developed a method for synthesizing surface-modified apatite nanoparticles that results in improved cell adhesion, offering new possibilities for the next generation of biocompatible medical implants. Led by Dr. Motohiro Tagaya, Associate Professor at the Department of Materials Science and Bioengineering at Nagaoka University of Technology, Japan, this research aims to enhance the performance of apatite coatings and advance the field of biocompatible materials for medical devices. The findings of this study were published online in ACS Applied Materials & Interfaces, on January 13, 2025, and in Volume 17, Issue 4 of the journal on January 29, 2025”. Along with Dr. Tagaya, Mr. Kazuto Sugimoto from Nagaoka University of Technology, Dr. Tania Guadalupe Peñaflor Galindo from Sophia University, and Mr. Ryota Akutsu from Nagaoka University of Technology were also a part of this research team.

Apatites are a class of calcium-phosphorus-based inorganic compounds, with hydroxyapatite—a naturally occurring form found in bones. These compounds are known for their high biocompatibility. Recent studies have foundthat coating artificial joints and implants with apatite nanoparticles is a plausible solution for improving the biocompatibility of these biodevices. However, the artificially synthesized nanoparticles often show reduced binding affinity to biological tissues in vitro. According to Dr. Tagaya and his team, this difference could be linked to the nanoscale surface layer of the apatite nanoparticles.

Dr. Tagaya’s research was driven by a desire to unravel the complexities of biocompatible materials, leading his team to develop an interdisciplinary framework that controls the intricate interactions between apatite and biological systems. “The properties of the nanoscale surface layer of apatite nanoparticles are crucial when considered for medical coatings,” adds Dr. Tagaya. Adding further, he says, “In this study, we successfully controlled the nanoscale surface layers of apatite nanoparticles, paving the way for advanced surface coating technologies for biodevices.”

The team synthesized hydroxyapatite nanoparticles by mixing aqueous solutions of calcium and phosphate ions. The pH of the solution was controlled using three different bases, which included tetramethylammonium hydroxide (TMAOH), sodium hydroxide (NaOH), and potassium hydroxide (KOH). The precipitated nanoparticles were then evaluated for their surface layer characteristics and were further used for coating via electrophoretic deposition.

The results revealed that pH was a key factor during synthesis, since it affected the crystalline phases, surface properties, and electrophoretic deposition. On analyzing the crystalline phases of the nanoparticles, it was observed that the choice of pH influenced the formation of different calcium phosphate phases like calcium-deficient hydroxyapatite (CDHA) and carbonate-containing hydroxyapatite (CHA). Higher pH favored the formation of CHA, leading to better crystallinity, and a higher calcium to phosphorus (Ca/P) molar ratio.

The surface of the apatite nanoparticles shows three different layers. The inner apatite layer/core is characterized by the presence of the crystalline structure of the apatite. Above the apatite layer is the non-apatitic layer, which is rich in ions like phosphate ions and carbonate ions. This layer reacts with water molecules and forms the hydration layer. Analyzing the surface characteristics of these layers revealed that pH adjustments facilitated the formation of the non-apatitic layer rich in reactive ions, enhancing hydration properties, which was confirmed.

Importantly, the study revealed that while higher pH facilitates the formation of the non-apatitic layer, the presence of Na+ ions reduces the concentration of phosphate ions, leading to decreased reactivity of the layer. The introduction of substantial ions by NaOH also affected the uniformity of electrophoretic deposition, as observed in scanning probe microscope studies. This effect was not observed with KOH, indicating that KOH was more suitable than NaOH for forming the non-apatitic layer and ensuring uniform coating.

Emphasizing the significance of the study, Dr. Tagaya says, “This study focuses on the critical interfacesbetween bioceramics and biological systems and could inspire designs of biocompatible surfaces with preferential cell adhesion.” These findings can be potentially useful for surface coating of a wide range of biodevices that are implanted in the human body, including artificial joints and implants.

Going ahead, the team intends to push the boundaries of nanobiomaterials, paving the way for groundbreaking innovations in medical materials and devices that could revolutionize healthcare and improve patient outcomes.

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

Surface State Control of Apatite Nanoparticles by pH Adjusters for Highly Biocompatible Coatings by Kazuto Sugimoto, Ryota Akutsu, Shota Yamada, Tania Guadalupe Peñaflor Galindo, Motohiro Tagaya. ACS Appl. Mater. Interfaces 2025, 17, 4, 7131–7141 DOI: https://doi.org/10.1021/acsami.4c18645 Published January 13, 2025 Copyright © 2025 American Chemical Society

This paper is behind a paywall.

What helps you may hurt you (titanium dioxide nanoparticles and orthopedic implants)

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From a Sept. 16, 2017 news item on Nanotechnology Now,

Researchers from the Mayo Clinic have proposed that negative cellular responses to titanium-based nanoparticles released from metal implants interfere in bone formation and resorption at the site of repair, resulting in implant loosening and joint pain. [emphasis mine]Their review of recent scientific evidence and call for further research to characterize the biological, physical, and chemical interactions between titanium dioxide nanoparticles and bone-forming cells is published in BioResearch Open Access, a peer-reviewed open access journal from Mary Ann Liebert, Inc., publishers. The article is available free on theBioResearch Open Access website.

A Sept. 14, 2017 Mary Anne Liebert (Publishing) news release, which originated the news item,  mentions the authors,

Jie Yao, Eric Lewallen, PhD, David Lewallen, MD, Andre van Wijnen, PhD, and colleagues from the Mayo Clinic, Rochester, MN and Second Affiliated Hospital of Soochow University, China, coauthored the article entitled “Local Cellular Responses to Titanium Dioxide from Orthopedic Implants The authors examined the results of recently published studies of titanium-based implants, focusing on the direct and indirect effects of titanium dioxide nanoparticles on the viability and behavior of multiple bone-related cell types. They discuss the impact of particle size, aggregation, structure, and the specific extracellular and intracellular (if taken up by the cells) effects of titanium particle exposure.

“The adverse effects of metallic orthopedic particles generated from implants are of significant clinical interest given the large number of procedures carried out each year. This article reviews our current understanding of the clinical issues and highlights areas for future research,” says BioResearch Open Access Editor Jane Taylor, PhD, MRC Centre for Regenerative Medicine, University of Edinburgh, Scotland.

Before getting to the abstract, here’s a link to and a citation for the paper,

Local Cellular Responses to Titanium Dioxide from Orthopedic Implants by Yao, Jie J.; Lewallen, Eric A.; Trousdale, William H.; Xu, Wei; Thaler, Roman; Salib, Christopher G.; Reina, Nicolas; Abdel, Matthew P.; Lewallen, David G.; and van Wijnenm, Andre J.. BioResearch Open Access. July 2017, 6(1): 94-103. https://doi.org/10.1089/biores.2017.0017 Published July 1, 2017

This paper is open access.

Indestructible spinal disc implants?

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This June 2, 2014 news item on Nanowerk is a bit confusing but despite all the talk about hips and knees the research described is largely concerned with spinal disc implants,

Artificial joints have a limited lifespan. After a few years, many hip and knee joints have to be replaced. Much more complex are intervertebral disc implants, which cannot easily be replaced after their “expiry date” and which up to now have had to be reinforced in most cases. This restricts the patient’s freedom of movement considerably. Researchers at Empa have now succeeded in coating mobile intervertebral disc implants so that they show no wear and will now last for a lifetime.

The May 28, 2014 Empa (Swiss Federal Laboratories for Materials Science and Technology) news release, which originated the news item, provides more details,

Due to the daily stresses and movement in the body, even the best artificial joints wear out; the material undergoes wear, and wear particles can trigger unwanted immune reactions, making it necessary to replace the joint. This is normally a standard procedure that can be repeated up to three times with most implants.  As bone material is lost each time an implant is explanted, the new joint has to replace more bone and is therefore larger. In the case of intervertebral discs, this is virtually impossible. They are too close to spinal nerves and tissue structures that could be damaged by another operation.

Up to now, intervertebral discs have not been replaced by mobile joints, but by so-called cages, a kind of place holder that both supports and allows the adjacent vertebrae to grow and fuse together. However, this causes stiffening at the point where previously the disc had provided adequate freedom of movement.  Over the years, this stiffening can result in the adjacent discs also having to be reinforced due to the increased stress on them. Mobile intervertebral disc implants could reduce this problem. However, many products currently available carry the risk of triggering allergies or rejection reactions due to material abrasion.

…

Initial attempts to increase the lifespan of artificial joints were made by various manufacturers in the past using a super-hard coating made of DLC (“diamond-like carbon”) – with disastrous consequences. Approximately 80% of DLC-coated hip joints failed within just eight years. Researchers at Empa’s “Laboratory for Nanoscale Materials Science” investigated this problem and found that the implant failure did not originate from the coating itself, but was caused by the corrosion behaviour of the bonding agent between the DLC layer and the metal body. This layer was made of silicon which corroded over the years, causing it to flake, which led to increased abrasion and, as a result, bone loss. “Our aim was to find a bonding agent which does not corrode and which lasts a lifetime in the body,” explains Kerstin Thorwarth.

…

This was a laborious task, as the Empa researcher emphasises: “We tried half the periodic table.”  One was finally found and tantalum was used as the bonding agent.  This coating was tested in a so-called total disc replacement – a mobile disc implant. We simulated 100 million cycles, i.e. about 100 years of movement in a specially designed joint simulator.  The small intervertebral disc implant held out, remaining fully operational with no abrasion or corrosion. The new bonding agent is soon also to be used in combination with DLC coatings for other joints. “The intervertebral disc is the most awkward joint in terms of implants. Because tantalum has performed so well, the DLC project can now be applied to other joints,” says Thorwarth.

If I understand the research rightly, proving that this technology does not wear out by testing it on the most difficult of the ‘joints’ to implant, an intervertebral disc, ensures success for ‘easier’ joints such as hips and knees.

I believe my most recent post about joint replacements is this Feb. 5, 2013 post which briefly mentions contrasting research approaches from Case Western University and MIT (Massachusetts Institute of Technology) while noting that people with joint replacements could be considered cyborgs.

The shrimp will save us

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Who knew that ceramics are a preferred material for body armour? Clearly, not me. According to the June 13, 2012 news item on Nanowerk, there’s a shrimp whose shell may offer inspiration for better quality ceramics used not only in military body armour but also in joint replacements. Here’s an image of one type of mantis shrimp,

Flower Mantis Shrimp (Photo Credit Silke Baron)

Pretty, isn’t it? Here’ s more from the June 13, 2012 news item on Nanowerk,

A scientist from Nanyang Technological University (NTU) may be onto an ocean of discovery because of his research into a little sea creature called the mantis shrimp.

The research is likely to lead to making ceramics – today’s preferred material for medical implants and military body armour – many times stronger. These findings were published in last Friday’s Science (“The Stomatopod Dactyl Club: A Formidable Damage-Tolerant Biological Hammer” [behind a paywall]), and focused on the mantis shrimp’s ability to shatter aquarium glass and crab shells alike.

The common creature native to the Indo Pacific, has club-like ‘arms’ which can strike prey at speeds matching that of a 5.56mm rifle bullet. Each impact generates a force exceeding 50 kilograms, which is hundreds of times the mantis shrimp’s weight.

The June 13, 2012 news release from Nanyang Technological University (Singapore) notes,

Assistant Professor Ali Miserez, from NTU’s School of Materials Science Engineering (MSE) and School of Biological Sciences (SBS), collaborated with Dr James Weaver from Harvard University as well as scientists from the University of California-Riverside, Purdue University, and Brookhaven National Laboratory in the United States.

They have observed down to the nanoscale the highly unique composite structure of the mantis shrimp’s club and discovered that it is weaved together in a unique fashion to create a structure tougher than many engineered ceramics. This is the first time that the mantis shrimp’s club is studied in such detail.

“The highly damage resistant property of the mantis shrimp could be most useful in medical products such as hip and joint implants, as they sustain impacts hundreds of times daily during walking and daily activities,” said Asst Prof Miserez, a recipient of the National Research Foundation Fellowship, which provides a research grant of up to S$3 million over five years.

“Damaged hip implants are a real problem, and cost billions of dollars to the healthcare systems worldwide. They also cause painful surgeries to patients when they need to be replaced. Using a nature-inspired blueprint to design biocompatible implants is actually a ‘shrimple‘ solution.”

Thank you for that wordplay. ‘Shrimple’, indeed! More seriously, I have previously commented on hip replacements and the search for ways to improve them, most recently in my April 20, 2012 posting.

The June 13, 2012 news release from Nanyang Technological University goes on to discuss Dr. Miserez’s lab and other applications for the shrimp-inspired ceramic materials,

Designing a damage-resistant implant which is made out of a bio-compatible bone material would solve the above problems [bone loss, toxicity, and immune reactions], as the material exists naturally in the human body. Asst Prof Miserez, whose laboratory is situated at MSE’s Centre for Biomimetic Sensor Science, said they will continue their research to better understand the design and materials and will attempt to replicate it in the laboratory next year.

His team, which includes PhD student Shahrouz Amini, will be focusing on developing a new bio-compatible material which could be used for medical implants such as hip implants. However, the potential applications for these nature-inspired designs are widespread because the final product is expected to be lighter weight and more impact resistant than existing products. These could include new types of armour plating, lighter vehicles and tougher engine and aircraft components like pistons and gears, all of which suffer from impact, wear and abrasion damage over time. [emphasis mine]

Possible medical and military advances march hand in hand, again!