A new technique could reduce the risk of blood clots associated with medical implants, making them safer for patients. The technique, which was developed by researchers at the University of Sydney, Australia, involves coating the implants with highly hydrophilic molecules known as zwitterions, thereby inhibiting the build-up of clot-triggering proteins.

Proteins in blood can stick to the surfaces of medical implants such as heart valves and vascular stents. When this happens, it produces a cascade effect in which multiple mechanisms lead to the formation of extensive clots and fibrous networks. These clots and networks can impair the function of implanted medical devices so much that invasive surgery may be required to remove or replace the implant.

To prevent this from happening, the surfaces of implants are often treated with polymeric coatings that resist biofouling. Hydrophilic polymeric coatings such as polyethylene glycol are especially useful, as their water-loving nature allows a thin layer of water to form between them and the surface of the implants, held in place via hydrogen and/or electrostatic bonds. This water layer forms a barrier that prevents proteins from sticking, or adsorbing, to the implant.

An extra layer of zwitterions

Recently, researchers discovered that polymers coated with an extra layer of small molecules called zwitterions provided even more protection against protein adsorption. “Zwitter” means “hybrid” in German; hence, zwitterions are molecules that carry both positive and negative charge, making them neutrally charged overall. These molecules are also very hydrophilic and easily form tight bonds with water molecules. The resulting layer of water has a structure that is similar to that of bulk water, which is energetically stable.

A further attraction of zwitterionic coatings for medical implants is that zwitterions are naturally present in our bodies. In fact, they make up the hydrophilic phospholipid heads of mammalian cell membranes, which play a vital role in regulating interactions between biological cells and the extracellular environment.

Plasma functionalization

In the new work, researchers led by Sina Naficy grafted nanometre-thick zwitterionic coatings onto the surfaces of implant materials using a technique called plasma functionalization. They found that the resulting structures reduce the amount of fibrinogen proteins that adsorb onto the implants by roughly nine-fold and decrease blood clot formation (thrombosis) by almost 75%.

Naficy and colleagues achieved their results by optimizing the density, coverage and thickness of the coating. This was critical for realizing the full potential of these materials, they say, because a coating that is not fully optimized would not reduce clotting.

Naficy tells Physics World that the team’s main goal is to enhance the surface properties of medical devices. “These devices when implanted are in contact with blood and can readily cause thrombosis or infection if the surface initiates certain biological cascade reactions,” he explains. “Most such reactions begin when specific proteins adsorb on the surface and activate the next stage of cascade. Optimizing surface properties with the aid of zwitterions can control / inhibit protein adsorption, hence reducing the severity of adverse body reactions.”

The researchers say they will now be evaluating the long-term stability of the zwitterion-polymer coatings and trying to scale up their grafting process. They report their work in Communications Materials and Cell Biomaterials.

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Orthopaedic implants that bear loads while bones heal, then disappear once they’re no longer needed, could become a reality thanks to a new technique for enhancing the mechanical properties of zinc alloys. Developed by researchers at Monash University in Australia, the technique involves controlling the orientation and size of microscopic grains in these strong yet biodegradable materials.

Implants such as plates and screws provide temporary support for fractured bones until they knit together again. Today, these implants are mainly made from sturdy materials such as stainless steel or titanium that remain in the body permanently. Such materials can, however, cause discomfort and bone loss, and subsequent injuries to the same area risk additional damage if the permanent implants warp or twist.

To address these problems, scientists have developed biodegradable alternatives that dissolve once the bone has healed. These alternatives include screws made from magnesium-based materials such as MgYREZr (trade name MAGNEZIX), MgYZnMn (NOVAMag) and MgCaZn (RESOMET). However, these materials have compressive yield strengths of just 50 to 260 MPa, which is too low to support bones that need to bear a patient’s weight. They also produce hydrogen gas as they degrade, possibly affecting how biological tissues regenerate.

Zinc alloys do not suffer from the hydrogen gas problem. They are biocompatible, dissolving slowly and safely in the body. There is even evidence that Zn²⁺ ions can help the body heal by stimulating bone formation. But again, their mechanical strength is low: at less than 30 MPa, they are even worse than magnesium in this respect.

Making zinc alloys strong enough for load-bearing orthopaedic implants is not easy. Mechanical strategies such as hot-extruding binary alloys have not helped much. And methods that focus on reducing the materials’ grain size (to hamper effects like dislocation slip) have run up against a discouraging problem: at body temperature (37 °C), ultrafine-grained Zn alloys become mechanically weaker as their so-called “creep resistance” decreases.

Grain size goes bigger

In the new work, a team led by materials scientist and engineer Jian-Feng Nei tried a different approach. By increasing grain size in Zn alloys rather than decreasing it, the Monash team was able to balance the alloys’ strength and creep resistance – something they say could offer a route to stronger zinc alloys for biodegradable implants.

In compression tests of extruded Zn–0.2 wt% Mg alloy samples with grain sizes of 11 μm, 29 μm and 47 μm, the team measured stress-strain curves that show a markedly higher yield strength for coarse-grained samples than for fine-grained ones. What is more, the compressive yield strengths of these coarser-grained zinc alloys are notably higher than those of MAGNEZIX, NOVAMag and RESOMET biodegradable magnesium alloys. At the upper end, they even rival those of high-strength medical-grade stainless steels.

The researchers attribute this increased compressive yield to a phenomenon called the inverse Hall–Petch effect. This effect comes about because larger grains favour metallurgical effects such as intra-granular pyramidal slip as well as a variation of a well-known metal phenomenon called twinning, in which a specific kind of defect forms when part of the material’s crystal structure flips its orientation. Larger grains also make the alloys more flexible, allowing them to better adapt to surrounding biological tissues. This is the opposite of what happens with smaller grains, which facilitate inter-granular grain boundary sliding and make alloys more rigid.

The new work, which is detailed in Nature, could aid the development of advanced biodegradable implants for orthopaedics, cardiovascular applications and other devices, says Nei. “With improved biocompatibility, these implants could be safer and do away with the need for removal surgeries, lowering patient risk and healthcare costs,” he tells Physics World. “What is more, new alloys and processing techniques could allow for more personalized treatments by tailoring materials to specific medical needs, ultimately improving patient outcomes.”

The Monash team now aims to improve the composition of the alloys and achieve more control over how they degrade. “Further studies on animals and then clinical trials will test their strength, safety and compatibility with the body,” says Nei. “After that, regulatory approvals will ensure that the biodegradable metals meet medical standards for orthopaedic implants.”

The team is also setting up a start-up company with the goal of developing and commercializing the materials, he adds.

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Analysing circulating tumour cells (CTCs) in the blood could help scientists detect cancer in the body. But separating CTCs from blood is a difficult, laborious process and requires large sample volumes.

Researchers at the K N Toosi University of Technology (KNTU) in Tehran, Iran believe that ultrasonic waves could separate CTCs from red blood cells accurately, in an energy efficient way and in real time. They publish their study in the journal Physics of Fluids.

“In a broader sense, we asked: ‘How can we design a microfluidic, lab-on-a-chip device powered by SAWs [standing acoustic waves] that remains simple enough for medical experts to use easily, while still delivering precise and efficient cell separation?’,” says senior author Naser Naserifar, an assistant professor in mechanical engineering at KNTU. “We became interested in acoustofluidics because it offers strong, biocompatible forces that effectively handle cells with minimal damage.”

Acoustic waves can deliver enough force to move cells over small distances without damaging them. The researchers used dual pressure acoustic fields at critical positions in a microchannel to separate CTCs from other cells. The CTCs are gathered at an outlet for further analyses, cultures and laboratory procedures.

In the process of designing the chip, the researchers integrated computational modelling, experimental analysis and artificial intelligence (AI) algorithms to analyse acoustofluidic phenomena and generate datasets that predict CTC migration in the body.

“We introduced an acoustofluidic microchannel with two optimized acoustic zones, enabling fast, accurate separation of CTCs from RBCs [red blood cells],” explains Afshin Kouhkord, who performed the work while a master’s student in the Advance Research in Micro And Nano Systems Lab at KNTU. “Despite the added complexity under the hood, the resulting chip is designed for simple operation in a clinical environment.”

So far, the researchers have evaluated the device with numerical simulations and tested it using a physical prototype. Simulations modelled fluid flow, acoustic pressure fields and particle trajectories. The physical prototype was made of lithium niobate, with polystyrene microspheres used as surrogates for red blood cells and CTCs. Results from the prototype agreed with numerical simulations to within 3.5%.

“This innovative approach in laboratory-on-chip technology paves the way for personalized medicine, real-time molecular analysis and point-of-care diagnostics,” Kouhkord and Naserifar write.

The researchers are now refining their design, aiming for a portable device that could be operated with a small battery pack in resource-limited and remote environments.

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Researchers in Australia have developed a nanosensor that can detect the onset of gestational diabetes with 95% accuracy. Demonstrated by a team led by Carlos Salomon at the University of Queensland, the superparamagnetic “nanoflower” sensor could enable doctors to detect a variety of complications in the early stages of pregnancy.

Many complications in pregnancy can have profound and lasting effects on both the mother and the developing foetus. Today, these conditions are detected using methods such as blood tests, ultrasound screening and blood pressure monitoring. In many cases, however, their sensitivity is severely limited in the earliest stages of pregnancy.

“Currently, most pregnancy complications cannot be identified until the second or third trimester, which means it can sometimes be too late for effective intervention,” Salomon explains.

To tackle this challenge, Salomon and his colleagues are investigating the use of specially engineered nanoparticles to isolate and detect biomarkers in the blood associated with complications in early pregnancy. Specifically, they aim to detect the protein molecules carried by extracellular vesicles (EVs) – tiny, membrane-bound particles released by the placenta, which play a crucial role in cell signalling.

In their previous research, the team pioneered the development of superparamagnetic nanostructures that selectively bind to specific EV biomarkers. Superparamagnetism occurs specifically in small, ferromagnetic nanoparticles, causing their magnetization to randomly flip direction under the influence of temperature. When proteins are bound to the surfaces of these nanostructures, their magnetic responses are altered detectably, providing the team with a reliable EV sensor.

“This technology has been developed using nanomaterials to detect biomarkers at low concentrations,” explains co-author Mostafa Masud. “This is what makes our technology more sensitive than current testing methods, and why it can pick up potential pregnancy complications much earlier.”

Previous versions of the sensor used porous nanocubes that efficiently captured EVs carrying a key placental protein named PLAP. By detecting unusual levels of PLAP in the blood of pregnant women, this approach enabled the researchers to detect complications far more easily than with existing techniques. However, the method generally required detection times lasting several hours, making it unsuitable for on-site screening.

In their latest study, reported in Science Advances, Salomon’s team started with a deeper analysis of the EV proteins carried by these blood samples. Through advanced computer modelling, they discovered that complications can be linked to changes in the relative abundance of PLAP and another placental protein, CD9.

Based on these findings, they developed a new superparamagnetic nanosensor capable of detecting both biomarkers simultaneously. Their design features flower-shaped nanostructures made of nickel ferrite, which were embedded into specialized testing strips to boost their sensitivity even further.

Using this sensor, the researchers collected blood samples from 201 pregnant women at 11 to 13 weeks’ gestation. “We detected possible complications, such as preterm birth, gestational diabetes and preeclampsia, which is high blood pressure during pregnancy,” Salomon describes. For gestational diabetes, the sensor demonstrated 95% sensitivity in identifying at-risk cases, and 100% specificity in ruling out healthy cases.

Based on these results, the researchers are hopeful that further refinements to their nanoflower sensor could lead to a new generation of EV protein detectors, enabling the early diagnosis of a wide range of pregnancy complications.

“With this technology, pregnant women will be able to seek medical intervention much earlier,” Salomon says. “This has the potential to revolutionize risk assessment and improve clinical decision-making in obstetric care.”

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