Day: 02/17/2024

Korean Scientists Develop Novel “Bone Bandage” Material for Cracked Bones

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A groundbreaking development in bone regeneration has been achieved with the creation of a piezoelectric scaffold by a KAIST-led research team. Utilizing hydroxyapatite (HAp) to generate electrical signals under pressure, this scaffold mimics the natural environment of bone tissue, showing promising results in promoting bone growth through both laboratory and animal studies. This advancement opens new pathways for biomaterial design and the understanding of bone regeneration processes.

Bone regeneration is a complicated procedure, and the current approaches for facilitating this regeneration, such as grafts and the application of growth factors, encounter challenges like elevated expenses. However, a breakthrough has been made with the creation of a piezoelectric material that has the capability to enhance bone tissue development.

A KAIST research team led by Professor Seungbum Hong from the Department of Materials Science and Engineering (DMSE) announced on January 25 the development of a biomimetic scaffold that generates electrical signals upon the application of pressure by utilizing the unique osteogenic ability of hydroxyapatite (HAp). This research was conducted in collaboration with a team led by Professor Jangho Kim from the Department of Convergence Biosystems Engineering at Chonnam National University.

HAp is a basic calcium phosphate material found in bones and teeth. This biocompatible mineral substance is also known to prevent tooth decay and is often used in toothpaste.

Breakthrough in Bone Regeneration

Previous studies on piezoelectric scaffolds confirmed the effects of piezoelectricity on promoting bone regeneration and improving bone fusion in various polymer-based materials, but were limited in simulating the complex cellular environment required for optimal bone tissue regeneration. However, this research suggests a new method for utilizing the unique osteogenic abilities of HAp to develop a material that mimics the environment for bone tissue in a living body.

Figure 1. Design and characterization of piezoelectrically and topographically originated biomimetic scaffolds. (a) Schematic representation of the enhanced bone regeneration mechanism through electrical and topographical cues provided by HAp-incorporated P(VDF-TrFE) scaffolds. (b) Schematic diagram of the fabrication process. Credit: KAIST Materials Imaging and Integration Laboratory

The research team developed a manufacturing process that fuses HAp with a polymer film. The flexible and free-standing scaffold developed through this process demonstrated its remarkable potential for promoting bone regeneration through in-vitro and in-vivo experiments in rats.

Understanding the Principles of Bone Regeneration

The team also identified the principles of bone regeneration that their scaffold is based on. Using atomic force microscopy (AFM), they analyzed the electrical properties of the scaffold and evaluated the detailed surface properties related to cell shape and cell skeletal protein formation. They also investigated the effects of piezoelectricity and surface properties on the expression of growth factors.

Figure 1. Design and characterization of piezoelectrically and topographically originated biomimetic scaffolds. (a) Schematic representation of the enhanced bone regeneration mechanism through electrical and topographical cues provided by HAp-incorporated P(VDF-TrFE) scaffolds. (b) Schematic diagram of the fabrication process. Credit: KAIST Materials Imaging and Integration Laboratory

Professor Hong from KAIST’s DMSE said, “We have developed a HAp-based piezoelectric composite material that can act like a ‘bone bandage’ through its ability to accelerate bone regeneration.” He added, “This research not only suggests a new direction for designing biomaterials, but is also significant in having explored the effects of piezoelectricity and surface properties on bone regeneration.”

New research helps create new antibiotic that evades bacterial resistance.

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UIC research helps create new antibiotic that evades bacterial resistance
T. thermophilus HB27 strain expressing Cfr-like methylase.

Scientists at the University of Illinois Chicago and Harvard University have developed an antibiotic that could give medicine a new weapon to fight drug-resistant bacteria and the diseases they cause.

The antibiotic, cresomycin, described in Science, effectively suppresses pathogenic bacteria that have become resistant to many commonly prescribed antimicrobial drugs.

The promising novel antibiotic is the latest finding for a longtime research partnership between the group of Yury Polikanov, associate professor of biological sciences at UIC, and colleagues at Harvard. The UIC scientists provide critical insights into cellular mechanisms and structure that help the researchers at Harvard design and synthesize new drugs.

In developing the new antibiotic, the group focused on how many antibiotics interact with a common cellular target—the ribosome—and how drug-resistant bacteria modify their ribosomes to defend themselves.

More than half of all antibiotics inhibit growth of pathogenic bacteria by interfering with their protein biosynthesis—a complex process catalyzed by the ribosome, which is akin to “a 3D printer that makes all the proteins in a cell,” Polikanov said. Antibiotics bind to bacterial ribosomes and disrupt this protein-manufacturing process, causing bacterial invaders to die.

But many bacterial species evolved simple defenses against this attack. In one defense, they interfere with antibiotic activity by adding a single methyl group of one carbon and three hydrogen atoms to their ribosomes.

Scientists speculated that this defense was simply bacteria physically blocking the site where drugs bind to the ribosome, “like putting a push pin on a chair,” Polikanov said. But the researchers found a more complicated story, as they described in a paper published last month in Nature Chemical Biology.

By using a method called X-ray crystallography to visualize drug-resistant ribosomes with nearly atomic precision, they discovered two defensive tactics. The methyl group, they found, physically blocks the binding site, but it also changes the shape of the ribosome’s inner “guts,” further disrupting antibiotic activity.

Polikanov’s laboratory then used X-ray crystallography to investigate how certain drugs, including one published in Nature by the UIC/Harvard collaboration in 2021, circumvent this common form of bacterial resistance.

“By determining the actual structure of antibiotics interacting with two types of drug-resistant ribosomes, we saw what could not have been predicted by the available structural data or by computer modeling,” Polikanov said. “It’s always better to see it once than hear about it 1,000 times, and our structures were important for designing this promising new antibiotic and understanding how it manages to escape the most common types of resistance.”

Cresomycin, the new antibiotic, is synthetic. It’s preorganized to avoid the methyl-group interference and attach strongly to ribosomes, disrupting their function. This process involves locking the drug into a shape that is pre-optimized to bind to the ribosome, which helps it get around bacterial defenses.

“It simply binds to the ribosomes and acts as if it doesn’t care whether there was this methylation or not,” Polikanov said. “It overcomes several of the most common types of drug resistance easily.”

In animal experiments conducted at Harvard, the drug protected against infections with multidrug-resistant strains of common disease drivers including Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Based on these promising results, the next step is to assess the effectiveness and safety of cresomycin in humans.

But even at this early stage, the process demonstrates the critical role that structural biology plays in designing the next generation of antibiotics and other life-saving medicines, according to Polikanov.

“Without the structures, we would be blind in terms of how these drugs bind and act upon modified drug-resistant ribosomes,” Polikanov said. “The structures that we determined provided fundamental insight into the molecular mechanisms that allow these drugs to evade the resistance.”

Have Chernobyl Mutations Rewired Evolution?

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From tree frogs to dogs, biologists have evidence of Chernobyl mutations in animals. What do these morphological changes mean for evolution?

Chernobyl dogs

Stray dogs in the Chernobyl Exclusion Zone.

The 1986 Chernobyl disaster was the worst nuclear meltdown in history. Today, much of the area around the old plant in Ukraine and in bordering Belarus remains uninhabited, including the city of the same name and Pripyat. But that’s only true if we’re talking about humans.

Many animals still live in the area. In many cases, wildlife populations have thrived due to the lack of human presence for more than 35 years. But does this mean the animals that live in the area have adapted to the unique threats they face from radiation in the area?

Some research suggests that populations in the Chernobyl Exclusion Zone have begun to evolve. Other researchers believe that there isn’t enough rigorous data yet to prove any kind of adaptive effect yet.

“We do the best we can with the resources we have at the time,” says Tim Mousseau, a biologist at South Carolina University who has tracked the development of radiation-prompted evolution for many years.

Chernobyl Frogs: Evolution in Action

In 2016, the researchers Pablo Burraco and Germán Orizaola began examining the way that eastern tree frogs were responding to radiation in the Chernobyl area. While normally bright green, these frogs are occasionally black.

In the Chernobyl area, however, they found many frogs displaying the uncharacteristic black color.

The melanin responsible for this dark color in various species can actually temper some of the negative effects of ultraviolet radiation. In humans, for example, dark pigmentation can protect from some of the negative effects of too much sunlight. Melanin also protects from some radiation-related cell damage.

Burraco and Orizaola expanded their study in the following years, analyzing the skin color of frogs captured from 12 ponds in northern Ukraine — including some in the most radioactive parts of the Chernobyl area. They compared these to frogs from other ponds outside the Chernobyl Exclusion Zone that had relatively low levels of radiation.

In all, the researchers analyzed more than 200 frogs and found that those from high radiation areas are much darker on average.

“Chernobyl frogs could have undergone a process of rapid evolution in response to radiation,” they reported in The Conversation. This is likely the result of natural selection, they say: Darker frogs survived at relatively higher proportions than their green counterparts.

Mutated Animals in Chernobyl

Also in 2016, Mousseau and a colleague published a review examining 17 cases where researchers claimed to find adaptations to radiation in Fukushima and Chernobyl. These included everything from pine trees to grasshoppers and voles.

The researchers failed to find strong evidence of adaptation in most of these studies, however, aside from the eradication of a few individuals that seemed to be genetically more vulnerable to the effects of radiation.

Many of the examined studies included relatively small sample sizes from single contaminated sites and single control sites. Or, they weren’t conducted with “significant rigor” to support a hypothesis of evolved adaptation, Mousseau says.

There was one exception: Researchers zapped the bacteria from the feathers of barn swallows in highly radiated parts of Chernobyl, as well as bacteria from Denmark with normal levels of radiation. They found that the bacteria on Chernobyl swallows is more resistant to damage caused by the induced radiation.

That’s not to say that Mousseau has ruled out evolution entirely. “I’m as guilty as any[one] of speculating about this,” he says. In fact, researchers have proven in several cases that evolution is possible within just a few generations. Mousseau simply believes that the studies so far haven’t been rigorous enough to support the idea.

Chernobyl Dogs

Feral dogs have also run wild in Chernobyl for more than 35 years. Many are the descendants of pets left behind during evacuation of the area. “People weren’t given much time to go,” says Elaine Ostrander, a geneticist at the National Institutes of Health.

In total, there may be thousands of feral dogs in the Chernobyl Exclusion Zone — their populations likely boosted by food given out by tourists, who are coming in increasing numbers to the area.

Mousseau and his colleagues connected with Ostrander and others to learn more about the genetic profile of these dogs; in research published recently in Science Advances, they analyzed DNA samples from 15 generations of feral dogs in Chernobyl.

“We were interested in identified variants in the DNA sequences that have allowed these dogs to live and propagate,” Ostrander says.

Their analysis revealed that different populations of dogs in the area had distinct signatures that identified where they came from. Those from the city of Chernobyl, for example, had a signature that was different from those at Pripyat, only 9 miles away. They also compared these with the genetic profiles of dogs that live in nearby Poland and elsewhere in Eastern Europe.

Doggone Radiation

The level of genetic detail that the researchers have examined in these dogs is unique, Mousseau says. But this research is only the first step.

Now that the genetic profiles of different Chernobyl dog populations have been characterized, the researchers can begin to examine whether there are common genetic threads between the Pripyat and Chernobyl dogs that differ, for example, from dog populations living with lower levels of radiation.

This kind of research may finally reveal how an animal that is relatively similar to humans responds and evolves to radiation.

“[Its] greatest potential, however,” write the study’s authors, “lies in understanding the biological underpinnings of animal and, ultimately, human survival in regions of high and continuous environmental assault.”