Tag Archives: bone

Researchers weave stem cells into most lifelike bone yet


Detail of bone tissue of tibia (malleolus medialis. Credit: Wikimedia Commons.

Scientists have coaxed stem cells to transform into bone tissue in the lab. The approach mimics real early bone formation and could be used to perform custom-made treatments, as well as pave the way for the development of lab-made fully functional bones.

“Having a fully functional bone is still far away, but we are sure that it will be achieved one day,” Anat Akiva, assistant professor of Cell Biology at Radboud University in the Netherlands, told ZME Science.

Along with colleagues from the Eindhoven University of Technology, the researchers combined their expertise to form an interdisciplinary team. This proved highly useful for tackling such a big challenge as growing bone in the lab.

Bone is a very complex material and how exactly it is formed in the body is not yet fully understood. Bone is essentially a complex matrix of collagen and minerals, with a lot of blood vessels.

To make bone, three types of cells come together in unison: osteoblasts (which build bone tissue), osteoclasts (which take bone away) and osteocytes (which regulate the building and breaking down of bone). 

Other research groups looking to grow bone tended to focus on only one of these types of cells. For their new study, the team from the Netherlands used stem cells to form two types of these cells (osteoblasts and osteocytes), which were ‘woven’ in a collagen matrix to form early-stage bone.

“Our bone from the lab is exactly like newly formed biological bone,” Akiva said, with the research showing that the mineralized matrix is similar in structure and chemistry.

This was the culmination of four years of extensive research, during which the researchers had to overcome a number of challenges.

“When we presented this research in one of the biggest bone conferences when we just started. We, of course, were thrilled with our study, but the audience, composed of bone scientists from every field, started to question our model and whether it is not good enough because we did not show specific things they were considering important. One of them told us: come back when you show that you have osteocytes – so we did. This means that actually already in 2017 we were the first ones to show that human stem cells can differentiate into osteocytes in the lab,” Akiva said.

Both the lab-grown bone and the biological bone that it mimics produce proteins that are required for the healthy functioning of bone. This means that the lab-grown version is ideal for use as a model system of human bone which can be used to test novel therapies.

From a research perspective, being able to replicate bone at the molecular level with such accuracy may be a new milestone. Bone is made of 99% collagen and minerals, but the remaining 1% of proteins is critical for functioning bone formation.

Many bone disorders, such as brittle bone disease, have their origin at the molecular level. Having a reliable model of the human bone could thus lead to great progress in medicine.

“We are now working in several directions: we are using genomic editing to label specific proteins to know when they are produced and to follow in real-time their journey from the cells to the collagen. By that, we hope to unravel the exact function of these different proteins in bone formation,” Akiva said.

“Another topic will be to grow and follow diseased osteoblast cells (such as in brittle bone disease/osteogenesis imperfecta) to understand at the molecular level why the bones of osteogenesis imperfecta patients are so fragile.”

“And last but not least we would like to go further than only the earliest form of bone formation, so integrating other cells will also be one of the next steps we envisage.”

The findings were reported in the journal Advanced Functional Materials.

Researchers confirm the first case of bone cancer in dinosaurs

Evidence is mounting that, despite living hundreds of millions of years ago, dinosaurs were not strangers to cancer.

An image and computerized scan of the bone.
Image credits Royal Ontario Museum / McMaster University.

Researchers have uncovered a new dinosaur fossil that seems to have suffered from a severe form of bone cancer around 77 million years ago. The findings help underscore the fact that cancer is in no ways a modern affliction — or a human-only one — and points to the role disease and other medical conditions play in the wild.

The bad bone

The research is based on the fossils of a Centrosaurus apertus, a herbivore that lived in the Canadian stretches during late Cretaceous (76 to 75 million years ago). Its life, at least during its latter parts, was probably not very enjoyable at all, as this dinosaur had to contend with a very aggressive case of bone cancer in one of its hind legs.

Not only would this make it difficult and painful for the dinosaur to move around — either to forage or to evade/fight off predators — but the team studying its fossil believes the cancer was malignant. If so, it means it could spread to its other tissues, mainly its internal organs.

The cancer in its leg bones was so advanced, that at first the team was convinced they were looking at a bone that had healed at sutured itself after a fracture. It was only after the bone was studied in depth using a host of techniques, including radiology and orthopedic surgery, that they found a massive, aggressive tumor inside the bone.

“Diagnosis of aggressive cancer like this in dinosaurs has been elusive and requires medical expertise and multiple levels of analysis to properly identify,” Dr. Mark Crowther, co-author of the study, said in a statement.

“Here, we show the unmistakable signature of advanced bone cancer in 76-million-year-old horned dinosaur—the first of its kind. It’s very exciting.”

The disease had progressed to an “advanced stage” by the time the animal died and likely made it very difficult for it to move. Still, it’s not all tragedy and woe with the dino: his remains were found in a “bone bed” along with many others from the same species. The team believes we’re looking at a pack of C. apertus that died in a flood. From the lack of bite marks on the diseased dino, and from his final resting place alongside his family and friends, it’s safe to assume that the herd lifestyle allowed it to survive despite his condition.

“The shin bone shows aggressive cancer at an advanced stage. The cancer would have had crippling effects on the individual and made it very vulnerable to the formidable tyrannosaur predators of the time,” adds Dr. David Evans, corresponding author of the study.

“The fact that this plant-eating dinosaur lived in a large, protective herd may have allowed it to survive longer than it normally would have with such a devastating disease.”

This isn’t the first time we’ve found evidence of tumors in dinosaur fossils, but it is the first confirmed case of bone cancer we’ve seen in such an animal.

The finding goes to show that even the mightiest animals sometimes have to bow in the face of disease. But it also shows how far we’ve come: dinosaurs, for all their might and long reign, were at the mercy of such conditions, and we’re starting to learn how to identify, manage, and cure them.

The paper “First case of osteosarcoma in a dinosaur: a multimodal diagnosis” has been published in the journal The Lancet.

Ancient 13,000-year-old bird figurine is the oldest Chinese 3D work of art

An international team of researchers has unearthed a beautifully preserved bone carving depicting a small bird at the Paleolithic site of Lingjing, in Henan, China. The ancient artwork, dated to between 13,800 and 13,000 years old, is the earliest 3D piece of art found in East Asia, pointing to a longstanding artistic tradition specific to the region.

Photo (top) and 3D reconstruction using microtomography (bottom) of the miniature bird sculpture. Credit: Francesco d’Errico and Luc Doyon.

Most ancient three-dimensional artworks have been discovered in Europe. In 2007, a team led by Nicholas Conard from the University of Tübingen in Germany excavated a tiny figurine of a woolly mammoth, measuring only 3.7 cm in length and weighing a mere 7.5 grams, from a site 1 km northwest of Stetten-ob-Lontal, Baden-Württemberg, Germany. Dated to 33,000 BCE, the mammoth figurine was skillfully carved, showing fine attention to detail.

Conard also discovered the oldest figurine depicting a human, a 35,000-year-old sculpture of a tiny figure, with short arms ending in five fingers. The Venus-like figurine was found three meters underground, within the Hohle Fels Cave in southern Germany.

Although the oldest known cave art — the 44,000 years old cave art of South Sulawesi, Indonesia — is located in East Asia, before the Lingjing discovery, the earliest three-dimensional animal sculpture from the continent was only 4,500 years old.

This has led some scholars to believe that there was quite an important lag between European and Asian hunter-gatherer cultures in 3-D artwork creation. Now, in a new study led by Zhanyang Li from Shandong University, China, archaeologists have cast new light on humanity’s earliest 3-D art.

Excavations at the Lingjing site first began in 2005, exposing 11 distinct stratified layers ranging in age from 120,000 years to the Bronze Age. However, the researchers realized they were in trouble. The fifth layer had been removed by a well-digging operation in 1958 — but not entirely.

A refuse heap from the time the well was built was still intact. Inside it, Li and colleagues found several artifacts, including shards of pottery, burned animal remains, as well as the bird figurine carved out of bone.

“The first time we looked at the figurine under the microscope we could not believe our eyes. Not only the traces of manufacture were well preserved. They clearly indicated that the artist was extremely skillful and able to adapt different techniques to carve each part of this tiny sculpture,” Francesco D’Errico of the Université de Bordeaux and corresponding author of the new study, told ZME Science.

3-D print of the original bone carving dated to 13,000 years ago. Credit: Francesco d’Errico.

Radiocarbon dating on the burned animal remains suggests that the bird figurine and associated bone material are about 13,000 years old. This predates previously known instances from this region by 8,500 years. The only other example of a bird figurine is a jade songbird sculpture dated to approximately 5,000 years ago.

“The oldest known statuettes, carved from mammoth ivory and depicting animals and humans, date to the Aurignacian period (40,000 years ago) and come from archaeological sites located in the Swabian Jura, Germany. For large areas of the world, however, it remains unclear when the production of three-dimensional representations became an integral part of the cultural repertoire of human societies, and whether this innovation was achieved independently or by diffusion from a center of origin. The discovery of this statuette, now the oldest work of Chinese art, sets back the origin of sculpture in East Asia by more than 8,500 years. Its stylistic and technological peculiarities – it is the only known Paleolithic sculpture of an animal standing on a pedestal – identify an original artistic tradition, unknown until now,” D’Errico said.

The findings appeared in the journal PLOS ONE.

Over 800 mammoth bones discovered in massive fossil stash in Mexico

If you like mammoths, you’re going to love this.

Archeologists from Mexico’s National Institute of Anthropology and History (INAH) reported finding the largest-ever body of mammoth remains. The trove includes 824 bones from at least 14 different animals and was unearthed in central Mexico.

Image credits Edith Camacho / INAH.

Even more excitingly, the team believes that this stash is the oldest known example of a mammoth trap or ambush, set by our ancestors over 14,000 years ago.

Big stash of bigger animals

“This is the largest find of its kind ever made,” the institute said in a statement (original text in Spanish).

The fossils were found in the municipality of Tultepec near the site where a new airport is under construction. The team reports that some of the bones found showed signs that the animals were hunted. As the bones are estimated to be around 14,000 to 15,000 years old, the team says this is the earliest example of such a trap ever found.

Two human-dug pits created in those days of yore were also found at the site, which the team believes were used to trap the animals. Each pit is about 1.7 meters deep and 25 meters in diameter. Remains of two other species that have gone extinct in the Americas — a horse and a camel — were also found.

“Mammoths lived here for thousands of years. The herds grew, reproduced, died, were hunted,” archaeologist Luis Cordoba told local media. “They lived alongside other species, including horses and camels.”

The two pits were found on a site that’s earmarked for use as a garbage dump. It’s still unclear whether work on the dump will proceed.

Injectable bone gel.

New “bone spackling” that can fix injuries with a simple injection shows promise in mice

Researchers at the University of Michigan want to make it possible for doctors to heal large bone injuries using a simple injection.

Injectable bone gel.

Nick Schott, graduate student research assistant at BME and one of the paper’s co-authors, working with the new compound.
Image credits Robert Coelius / Michigan Engineering.

Large or complex bone fractures are a nightmare to fix for patients and doctors both. They often require grafts and multiple surgeries to properly address, which is a long, expensive, and quite stressful process for everyone involved. So Jan Stegemann a professor of biomedical engineering at the University of Michigan and his team are working on reprogramming progenitor cells so they can be injected directly into a wound and grow into solid bone. Progenitor cells are adult bone marrow stem cells that can differentiate into several functions (i.e. morph into other cell types).

Bone-a-fide bone fixer

We’re targeting large, complex defects, where a lot of bone has been lost and the tissue around the bone has been damaged,” Stegemann explains. “These wounds don’t always heal, and they can be highly debilitating. Sometimes the muscle and surrounding blood vessels have been disturbed.”

“There are treatments to stabilize the bone and even fillers you can put in to try to help the bone regenerate, but these options are not suitable in all cases and current treatments are not ideal — they don’t work for some of the most serious cases.”

Right now, the only treatment option for patients with this kind of injury is to receive a graft from another part of their body. For example, doctors will harvest bone from a patient’s hip, crush it up, and plaster it into the wound to help that bone regenerate. It works, but it involves several rounds of surgery (one to collect the material, one to graft it in if no complications arise).

The team wanted to devise a way to actually regenerate living bone, and for that, they needed living cells. You could do it in much the same way as with the bone — graft these cells from other areas of the body and use them to regenerate the bone. However, that still poses the same problems and unpleasantness. What the team did instead was to harvest progenitor cells from the patient, grow them in the lab, and nudge them into creating bone tissue. They are then used like a drug — injected into the damaged area.

This approach, the team explains, is intended to make the cells more likely to survive and regenerate bone where it is needed. Progenitor cells can be “derived from the bone marrow or other tissues” according to Stegemann, “even from liposuctioned fat”.

“You can isolate those cells and then expand their number until you have many multiples of the initial number of cells that you took from the body,” he explains. “You can also treat them so that they form the type of tissue you are interested in.”

The researchers treat these cells with specific biological molecules that make them differentiate into bone cells. Furthermore, specialized biomaterial is used to bind the progenitor cells together and further coax them into creating bone. These “microtissues” as the team calls them are essentially small beads of proteins containing tens to hundreds of cells inside each. The microtissues are meant to feed and promote the survival and function of the cells after they’re transplanted into the bone, as this is a kind of tissue that doesn’t get a sizable blood supply and tends to trigger inflammation in surrounding tissues when damaged. This makes it likely that the injected cells will die or migrate away before they actually begin regenerating the tissue.

Through the combination of these two approaches, the cells are made to “to really potently regenerate new tissue”. Millions of these microtissues can be produced in a single batch, the team explains. Overall, the end product looks like a slurry — Stegemann likens it to spackling compound that can be used to repair damaged drywall — which is injected directly into the damaged bone. Because the delivery can be performed with a simple needle, there is a good chance that doctors can avoid having to perform a surgery.

Right now, the team is testing their approach on mice.

“The work that we’ve accomplished so far has shown very clearly that our biomaterials-based approach has a lot of merit,” Stegemann explains. “We are able to consistently control cell function and cell phenotype to regenerate tissue types that we’re interested in — most specifically bone right now.”

“We’ve shown that the idea of creating these little microtissues, culturing them outside the body and priming them to regenerate bone before we transplant, has merit as well. And we’ve validated that the culturing process, and delivering them in conjunction with a biomaterial, very significantly increases the amount of bone that you can regenerate.”

The team says that their method can be further developed to work with other types of tissues.

The paper “Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects” has been published in the journal Biomaterials.

Sticks and stones will break your bones, then this new cellulose aerogel will heal them

Bone implants are poised to receive an upgrade, as researchers from the University of British Columbia and McMaster University have developed a new foam-like substance for this purpose.

Foam bone cure.

The aerogel derived from plant cellulose.
Image credits Clare Kiernan / UBC.

Most bone implants today are made of hard ceramics. They’re hardy enough for the job, but the material is also very brittle, making it hard to work with. It’s also very tricky getting these implants to conform to the shape of the fractures or holes in the damaged bone — which often leads to the implant failing.

Sponge it

“We created this cellulose nanocrystal aerogel as a more effective alternative to these synthetic materials,” said study author Daniel Osorio, a Ph.D. student in chemical engineering at McMaster.

The team developed a foam-like substance (aerogel) that can be injected into damaged bones to provide scaffolding for the growth of new tissue. It’s formed of nanocrystals obtained from treated plant cellulose which can link up to form a strong but lightweight ‘sponge’ which is strong but also capable to expand or compress in order to fill out a cavity.

In order to test their aerogel, the team worked with two groups of rats. The first received the aerogel implants while the second (control group) received none. Over a three-week period, the first group saw 33% more bone growth and 50% more bone growth by the 12-week mark compared to the control group.

The team says these results show that cellulose nanocrystal aerogels are a viable, even preferable, medium to support bone growth. The implants will break down over time into non-toxic components in the body as bones heal, they add, limiting the need for further invasive procedures and treatments. All in all, even if the material doesn’t remove traditional implants, it is bound to find use as a supportive or novel treatment avenue in lieu of traditional materials.

“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.”

That being said, we’re still a ways away until the aerogel is ready for use in operating rooms across the world.

“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.”

The paper “Cross-linked cellulose nanocrystal aerogels as viable bone tissue scaffolds” has been published in the journal Acta Biomaterialia.

Trans-cortical vein canals move bone marrow cells and potentially facilitate the exchange of nutrients between the bone and the general circulation system. Credit: Nature.

Scientists find hidden blood vessels inside bone

Trans-cortical vein canals move bone marrow cells and potentially facilitate the exchange of nutrients between the bone and the general circulation system. Credit: Nature.

Trans-cortical vein canals move bone marrow cells and potentially facilitate the exchange of nutrients between the bone and the general circulation system. Credit: Nature.

Researchers have long suspected that bones have a complex blood supply but due to limited imaging methods, it has always been challenging to prove it — until now. A research team from the University Duisburg-Essen, Germany, used modern imaging technologies showing that long bones, such as shinbones, are crossed perpendicularly by tiny canals.

The researchers use a special technique called ‘clearing’ which makes bones transparent, revealing hundreds of tiny capillaries crossing the hard outer shell of the bone of mice. Called ‘trans-cortical vessels’ (TCVs), these channels seem to play an active and crucial role in the circulatory system of rodents. This may apply to humans as well, judging from similar, thicker, canals found in human long bones — whether or not these are TCVs is to be determined.

According to a calculation performed by the team led by Matthias Gunzer, most of the blood passing through bones flow through TCVs. And this way, the researchers conclude, bone marrow is connected to a wider circulatory system throughout the body. This explains why, during an emergency, drug infusions into the bone marrow rapidly spread to the rest of the body.

The researchers also investigated whether TCVs might have a role in inflammatory and degenerative bone disorders. The authors observed that mice with acute, inflammatory arthritis had more TCVs in their bones. The TCVs were lined with endothelial cells that engage with inflammatory cells, as reported in the journal Nature.

The presence of TCVs in human bone requires confirmation, along with a direct link between TCVs and inflammatory diseases.

Since the dense vascular network facilitates the movement of bone marrow cells and nutrients — but also immune cells — they could be targeted by novel therapies. For instance, potential new treatments for bone inflammation and tissue injuries might involve drugs that regulate blood flow or cell migration through the TCVs.

n: Strings of a polymerised liquid crystal act as the strings of collagen in the body. The amorphous calcium phosphate (in grey) enters the strings and begins to crystallise, creating the artificial bone-like material. ​ ​Illustration: Anand Kumar Rajasekharan/Chalmers University of Technology.

Scientists learn how bone grows atom by atom, which could lead to better osteoporosis treatment

Swedish researchers were looking to create artificial bone, but in doing so they may have come across something more important. By analyzing the process of their bone imitation, the researchers were able to study how our bones grow at an atomic level, morphing from an unstructured mass into a perfectly arranged structure.

n: Strings of a polymerised liquid crystal act as the strings of collagen in the body. The amorphous calcium phosphate (in grey) enters the strings and begins to crystallise, creating the artificial bone-like material. ​ ​Illustration: Anand Kumar Rajasekharan/Chalmers University of Technology.

Strings of a polymerized liquid crystal act as the strings of collagen in the body. The amorphous calcium phosphate (in grey) enters the strings and begins to crystallize, creating the artificial bone-like material. Illustration: Anand Kumar Rajasekharan/Chalmers University of Technology.

It’s a well-established fact that our bones grow in stages, but what exactly goes on in each of these stages had previously been a mystery. Martin Andersson, Professor in Materials Chemistry at Chalmers University of Technology, Sweden, along with colleagues, developed a method for creating artificial bone using 3-D printing. Once this technology is fully developed, the team hopes to create nature-mimicking implants that might replace metal and plastic implants currently in use.

However, while Andersson and colleagues were printing bones, they couldn’t help but notice that their process was extremely similar to the environment that living tissue grows in. Using electron microscopes, the team studied how material turned from an amorphous mush into an orderly structure that resembles bone, all at the atomic level.

“A wonderful thing with this project is that it demonstrates how applied and fundamental research go hand in hand. Our project was originally focused on the creation of an artificial biomaterial, but the material turned out to be a great tool to study bone building processes. We first imitated nature, by creating an artificial copy. Then, we used that copy to go back and study nature,” Andersson said in a statement.

Diagram describing a possible bone mineralisation mechanism. Credit: Nature Communications.

Diagram describing a possible bone mineralisation mechanism. Credit: Nature Communications.

Writing in the journal Nature Communicationsthe Swedish researchers explain how bone mineralization first starts with strings of the protein collagen — the smallest structural building block in the skeleton. Cells then send spherical particles called vesicles to the site, where they bind between the collagen strings. There, the vesicles, which are made of calcium phosphate, transform from an amorphous mass into an ordered crystalline structure.

The crystallization process is not biological but rather purely physical, following the laws of thermodynamics. The calcium phosphate molecules are drawn to where the energy level is the lowest, and therefore where there is a more stable state.

These findings could prove highly useful, not only in manufacturing nature-mimicking bones for implants but also for treating bone diseases.

“Our results could be significant for the treatment of bone disease such as osteoporosis, which today is a common illness, especially among older women. Osteoporosis is when there is an imbalance between how fast bones break down and are being reformed, which are natural processes in the body,” said Martin Andersson.

Drugs that seek to address this imbalance may be improved thanks to this study’s newfound knowledge, the authors conclude.

The earliest vertebrates with a mineralised skeleton were armoured jawless fishes such as Anglaspis heintzi, a heterostracan that lived approximately 419 million years ago. Credit: Wikimedia Commons.

Earliest evidence of bone solves mysterious origin of our skeletons

The earliest vertebrates with a mineralised skeleton were armoured jawless fishes such as Anglaspis heintzi, a heterostracan that lived approximately 419 million years ago. Credit: Wikimedia Commons.

“The earliest vertebrates with a mineralized skeleton were armored, jawless fish like Anglaspis heintzi, a heterostracan that lived approximately 419 million years ago. Credit: Wikimedia Commons.

For 160 years, scientists have been debating what tissue types made up the earliest vertebrate skeletons. Now, a new study that used powerful X-rays to peer inside a 400-million-year-old fossilized skeleton has finally cracked this mystery. Researchers concluded that a “spongy” tissue called aspidin was used in the earliest evidence of bone in the fossil record.

The very first bones were dramatically different from our own

Today, the skeletons of vertebrates are built out of four different tissue types. These are bone, cartilage, (a rubber-like padding that covers and protects the ends of long bones at the joints and is a structural component of many body parts), dentine, and enamel. Dentine is the hardest material in the body because of its high inorganic content and low water composition, while enamel is the outermost layer that covers dentine.

These tissues become mineralized as they grow, offering the skeleton strength and rigidity. Millions of years ago, however, there were likely other types of tissue that constructed bones.

To get to the bottom of things, a team of researchers at the University of Manchester, the University of Bristol and the Paul Scherrer Institute in Switzerland examined in excruciating detail the fossils of a group of fish called heterostracans, which lived 400 million years ago. In order to peer inside the ancient skeletons, the researchers employed a special type of CT scan which uses high energy X-rays produced by a particle accelerator. It was all a laborious process, however, which involved scanning different heterostracan species and requiring numerous trips to the Swiss Light Source, Switzerland and over 100 hours of scanning time.

High-power X-rays allowed researchers to create detailed models of the skeletal tissue. Credit: Keating et al. 2018.

High-power X-rays allowed researchers to create detailed models of the skeletal tissue. Credit: Keating et al. 2018.

This technique allowed the researchers to discover what kind of tissue heterostracan skeletons are made of. Heterostracans are some of the oldest vertebrates with a mineralized skeleton and by studying them, it is possible to deconstruct what the earliest bones looked like and how they transitioned to their current form.

“When we had collected the data, I began the painstaking process of creating a 3D digital model of aspidin, in order to determine the shape and orientation of the mysterious tubes. Images from previous studies seem to show the tubes branching; resembling the branching processes of bone cell-spaces. However, I found that these tubes were strictly linear, lacking any kind of branching. The images from previous studies seem to be a result of 2-dimensional sectioning through tangled and overlapping tubes, giving the appearance of branching. This discovery was an important piece in the puzzle, allowing me to rule out the possibility that these tubes were bone or dentine cell-spaces,” Dr. Joseph Keating, from Manchester’s School of Earth of Environmental Scientists, told ZME Science.

According to the results, heterostracan skeletons were made of aspidin — a strange tissue, crisscrossed by tiny tubes, which doesn’t even remotely resemble any other tissue found in vertebrates today.

 

Researchers were able to identify the mysterious tissue ‘aspidin’ and provide new insight into the evolution of our skeleton. Credit: Keating et al.

Researchers were able to identify the mysterious tissue ‘aspidin’ and provide new insight into the evolution of our skeleton. Credit: Keating et al.

Keating and colleagues conclude that these tiny tubes used to house fiber-bundles of collagen inside them. Collagen is a type of protein found in the skin and bones.

However, heterostracan skeletons bear some important differences when compared to modern vertebrate bones.

“Heterostracan aspidin lacks two key features of bone in most living vertebrates. Firstly, aspidin is acellular: it lacks cell spaces, as our research has revealed. The bone of most modern vertebrates, including humans, contains a network of interconnected spaces housing living cells, called osteocytes, that maintain bone tissue,” Keating said.

“Secondly, The bone of modern vertebrates is constantly restructured via a process called resorption, whereby bone cells called osteoclasts break down the mineralised tissue. New mineralised tissue is then deposited by another type of bone cell called osteoblasts. This ability allows our skeletons to grow dynamically through life. Heterostracan skeletons show some evidence of resorption, but it appears to be much less common than in the skeletons of most living vertebrates.”

“These two features of modern bone evolved later in vertebrate evolution.”

Aspidin was once thought to be the precursor of vertebrate mineralized tissues. These findings published in Nature Ecology and Evolution suggest that aspidin is, in fact, the earliest evidence of bone in the fossil record, changing our view of the evolution of the skeleton.

“Our results suggest that all types of mineralised tissues found in living vertebrates appear simultaneously in the fossil record, around 420 million years ago. This raises two important questions: when did these tissues first evolve? And why do they appear in the fossil record at the same time? One possible explanation is that the sudden appearance of mineralised tissues is due to the evolution of mineralisation, rather than the evolution of the tissues themselves. Bone and dentine may have first evolved as distinct layers of the skin long before vertebrates evolved the genetic pathways necessary for tissue mineralisation. As such, the early history of these tissues may not be preserved in the fossil record, as unmineralised tissues are prone to decay. Alternatively, there may be a missing fossil record of older vertebrates showing earlier stages in the evolution of the skeleton. These may be fossils we are yet to discover, or fossils sitting in museum draws which have not yet been recognized for their significance,” Keating told ZME Science.

Fox spine.

Bones have a fractal-like structure making them super strong and flexible

Zoom in close enough and bones betray an incredible structural sophistication.

Fox spine.

Fragment of fox spine.
Image via Pixabay.

Researchers from the University of York and the Imperial College London have produced a 3D, nanoscale reconstruction of bone’s mineral structure. Their work reveals a surprising ‘hierarchical organisation’ which underpins the material’s mechanical versatility.

Bred in the bones

Bone is a surprisingly versatile material. Different varieties of bone can be both strong and flexible, maintaining the lithe form of cheetas, the impressive bulk of elephants, or the lightweight frames of birds alike.

These enviable properties are owed to a sophisticated internal structure. However, the exact nature of this structure and of the interactions between the main components of bone — collagen protein strands and the mineral hydroxyapatite — has so far been unknown. According to new research, however, the ‘hierarchical organization’ of bone is based on small elements coming together to form larger and larger structures.

Their results have shown that individual mineral crystals inside bone tissue come together into larger, more complex structures — ones that come together into even more complex levels of organization, the team reports.

For the findings, the team used advanced 3D nanoscale imaging of the mineral component of human bone. They used a combination of electron microscopy-based techniques to reveal its main mineral building blocks. These nanometer-sized crystals of apatite take on a curved, needle-like shape and merge together into larger, twisted platelets that resemble the shape of propeller blades.

These blades, in turn, merge together and split apart throughout the protein phase of the bone. This overarching weaving pattern of mineral and protein is what provides the material’s strength and flexibility.

“Bone is an intriguing composite of essentially two materials, the flexible protein collagen and the hard mineral called apatite,” Lead author, Associate Professor Roland Kröger, says Associate Professor the University of York’s Department of Physics, lead author of the paper.

“The combination of the two materials in a hierarchical manner provides bone with mechanical properties that are superior to those of its individual components alone and we find that there are 12 levels of hierarchy in bone.”

The paper describes the structure as “fractal-like”, containing 12 different levels of complexity. The needle-like crystals merge into the propeller-like platelets in a roughly parallel arrangement with gaps of roughly 2 nanometers between them. These stacks of platelets, along with some single platelets and acicular crystals, come together into larger “polycrystalline aggregates”. These latter ones are larger laterally than the collagen fibers, and can even span several adjacent fibers — providing a continuous, cross-fiber mineral structure that lends resilience to the bone.

Bone structure.

The model of crystal organization in bone proposed by the team.
Patterns specified by the model at the top alongside the mineral organization in different directions (bottom).
Image credits N. Reznikov et al., 2018, Science.

These nanostructures woven into the bone also show a slight curvature, twisting the overall geometry, the team further reports. For example, the individual crystals are curved, the protein (collagen) strands are braided together, mineralized collagen fibrils twist, and the bone themselves have a twist (such as a curvature of a rib).

The team concludes that this fractal-like structure they discovered embedded in our bones is one of the cornerstones of their remarkable physical properties.

The paper “Fractal-like hierarchical organization of bone begins at the nanoscale” has been published in the journal Science.

A handout picture released from researcher Nathaniel Dominy shows a human thigh bone dagger attributed to the Upper Sepik River (up) and cassowary bone dagger attributed to the Abelam people (down). Credit: Dartmouth College.

New Guinea warriors used human bone daggers — and these are remarkably strong

For centuries, New Guinea natives have crafted bone knives and daggers used for hunting, fighting, and for ceremony. Most are made from the thighbones of cassowaries, which are large, ostrich-like birds. However, some of the daggers are made from human bone — specifically, the thighbone of an ancestor or highly respected member of the tribe — and these are remarkably resilient. In fact, some scientists actually measured the strength of human bone daggers and compared them to the cassowary variety, finding the former is almost twice as strong.

A handout picture released from researcher Nathaniel Dominy shows a human thigh bone dagger attributed to the Upper Sepik River (up) and cassowary bone dagger attributed to the Abelam people (down). Credit: Dartmouth College.

A handout picture released by researcher Nathaniel Dominy shows a human thigh bone dagger attributed to the Upper Sepik River (up) and cassowary bone dagger attributed to the Abelam people (down). Credit: Dartmouth College.

New Guinea tribes are no strangers to weird and peculiar traditions, to use a euphemism, at least to us westerners. Take the Edoro, for instance, an ethnic New Guinea tribe whose range comprises the southern slopes of Mt. Sisa, and who are famous to anthropologists for the ritual pedophilic homosexual acts they practice. The Etoro believe that young boys must ingest the semen of their elders daily from the age of 7 until they turn 17 to achieve adult male status and to properly mature and grow strong. What’s more, among the Etoro, heterosexual intercourse — which they believe makes men die early — is prohibited for up to 260 days of the year and forbidden in or near their houses and vegetable gardens. In contrast, homosexual relations — which the Etoro believe prolong life — are permitted at any time.

A more widespread practice among New Guinea tribes is crafting bone daggers. Nathaniel Dominy, a professor of anthropology at Dartmouth College, got the idea to investigate such weapons after he came across an impressive stash of daggers at the university’s Hood Museum of Art, which were carved out of cassowary and human thighbones. These were like exquisite works of art, featuring elaborate motifs carved into them.

Dominy claims that the daggers were used to kill or finish off victims wounded with arrows or spears, by stabbing them in the neck. There are also accounts from the 1800s and early 1900s that the bone daggers were used for mutilation and cannibalism, but such statements are difficult to verify. Dominy says that these old accounts made by outsiders, such as missionaries, are prone to exaggerations and cultural misinterpretations.

What’s certain, the researchers say, is that the manufacturing of the human bone dagger had a deep cultural significance. Typically, such a dagger was fashioned out of the thighbone of a very important person in the community, either the father of the warrior or some other respected person in the community. This way, the warrior carried the rights and power of the person from which the bone came.

“The human bone dagger is stronger because men gave it a slight different shape—it has greater curvature,” Dominy told AFP.

“We believe that such a shape was done deliberately to minimise the chance of the dagger breaking during fighting. And the reason that men engineered human bone daggers to resist breaking is because human bone daggers carried a lot of social prestige.”

Closeup of a terryfing cassowary claw -- the real life, modern-day Velociraptor. Credit: Featured Creature.

Closeup of a terrifying cassowary claw — the real life, modern-day Velociraptor. Credit: Featured Creature.

The most common type of New Guinea dagger, however, is made from the cassowary. Although it might look relatively harmless, don’t let its appearance deceive you — this is one of the most dangerous birds in the world. It’s the second heaviest in the world after its cousin, the ostrich, and each of its feet boasts a razor-sharp claw that can grow to 4.7 in. (12 cm) in length. With an agile kick, a predator can be easily maimed or killed. What’s more, the bird can jump almost 5 feet (1.5 m) high and can run up to 31 mph (50 km/h). So, it’s not very surprising that New Guinea locals used the cassowary’s claw to fashion daggers out of.

In order to see which of the types of daggers is stronger, the researchers performed computed tomography (CT) scans of five cassowary daggers and five human-bone daggers. The scans enabled the researchers to determine the density of each dagger. Apparently, both types of bones ‘are equally good for making daggers.’ However, when an additional cassowary-bone dagger — which was bought especially for this study — was destroyed in a bending test to see how much force it could take before breaking, the weapon proved far inferior to the human bone one. The test showed that the bird bone weapon could handle up to 44 lbs (200 newtons) of force before breaking, while the human bone dagger could withstand twice as much force. The researchers say that it’s likely that the human daggers are stronger because they crafted with greater care, seeing how they were a lot rarer and more valuable than the bird-bone daggers.

The findings were reported the journal Royal Society Open Science.

Augmented Reality could soon help surgeons ‘see’ through the skin

From Pokemon to saving lives: using augmented reality in the operating room could usher in a new age of surgery.

The surgeon’s vision — elements of the patient’s foot were digitized and then fed into a 3D model. Image credits: Philip Pratt et al. Eur Radiol Exp, 2018 / Microsoft HoloLens (c) Microsoft.

Augmented Reality, the technique popularized last year by Pokemon Go, overlays real-life elements with “augmented” bits — most often, computer-generated information. It’s a world where real life as we know it interacts with holograms.

Now, for the first time, doctors have used augmented reality as an aid for surgery. Specifically, they’ve used Microsoft HoloLens headsets to overlay CT scans, indicating the position of bones and key blood vessels, over each of the patient’s legs. Basically, they were able to ‘see’ through the patient’s skin.

The technology helped with a very delicate procedure: the reconnecting of blood vessels, an essential part of reconstructive surgery.

“We are one of the first groups in the world to use the HoloLens successfully in the operating theatre,” said Dr. Philip Pratt, a Research Fellow in the Department of Surgery & Cancer and lead author of the study, published in European Radiology Experimental.

“Through this initial series of patient cases we have shown that the technology is practical, and that it can provide a benefit to the surgical team. With the HoloLens, you look at the leg and essentially see inside of it. You see the bones, the course of the blood vessels, and can identify exactly where the targets are located.”

So far, the technology has only been used in reconstructive limb surgery, but there’s no reason why it couldn’t be adapted to other types of surgery. Image credits: Philip Pratt et al. Eur Radiol Exp, 2018 / Microsoft HoloLens (c) Microsoft.

Doctors carried out five surgeries using the technology. Prior to the surgery, CT scans mapped the structure of the limb. The elements revealed by the CT scan were then split into bone, muscle, fatty tissue and blood vessels by Dr. Dimitri Amiras, a consultant radiologist at Imperial College Healthcare NHS Trust. Amiras used the data to develop a 3D model of the patients’ legs. The models were fed into the HoloLens, allowing surgeons to see them as they were carrying out the procedure. The surgeons also fine-tuned the model — with a simple hand gesture, they made sure that the model lined up with real life.

The procedure is time-consuming but in the future, algorithms could greatly simplify and reduce the work volume.

“The application of AR technology in the operating theatre has some really exciting possibilities,” said Jon Simmons, a plastic and reconstructive surgeon who led the team. “It could help to simplify and improve the accuracy of some elements of reconstructive procedures.

“While the technology can’t replace the skill and experience of the clinical team, it could potentially help to reduce the time a patient spends under anaesthetic and reduce the margin for error. We hope that it will allow us to provide more tailored surgical solutions for individual patients.”

Right now, the technique has only been used for lower limb reconstructive surgery, but the proof of concept is there. This study shows that the technology is practical, accurate, and safe to use. There’s no reason why a similar approach couldn’t be used in different types of surgery.

Augmented reality does nothing to replace the skill and experience of the operating team, but it does complement and amplify it, significantly reducing the margin for error.

The paper ‘Through the HoloLens looking glass: augmented reality for extremity reconstruction surgery using 3D vascular models with perforating vessels’ by Philip Pratt et al. is published in the journal European Radiology Experimental.

Chameleons display fluorescent bones on the skull, study shows

The lizard master of disguise is surely a very special creature, we can all agree. Researchers discovered a new outstanding feature of the chameleon: its bones shine with a blue hue in UV light.

Fluorescent tubercles showing sexual dimorphism under UV light at 365 nm (A–D) and fluorescence in further chameleon genera (E–G). (A) Male Calumma crypticum ZSM 32/2016. (B) Female C. crypticum ZSM 67/2005. (C) Male C. cucullatum ZSM 655/2014. (D) Female C. cucullatum ZSM 654/2014. (E) Brookesia superciliaris, male (only UV light at 365 nm). (F) Bradypodion transvaalense, male (dim light and additional UV light at 395 nm). (G) Furcifer pardalis, male (daylight and additional UV light at 365 nm).

Bioluminescence is not that uncommon among marine creatures and some insects (see fireflies), but most terrestrial animals don’t quite possess this eye-endearing feature. The fact that researchers found biogenic fluorescence in chameleons — an entirely earthbound animal — is surprising.

Male C. globifer (ZSM 141/2016) showing congruent tubercle/fluorescent patterns (from left to right); top row: alive in the field under sunlight, micro-CT scan of head surface (probable edge artefact in cheek region), micro-CT scan of the skull; bottom row: alive in the field under UV light, ethanol-preserved under UV light.

Male C. globifer (ZSM 141/2016) showing congruent tubercle/fluorescent patterns (from left to right); top row: alive in the field under sunlight, micro-CT scan of head surface (probable edge artefact in cheek region), micro-CT scan of the skull; bottom row: alive in the field under UV light, ethanol-preserved under UV light.

“We could hardly believe our eyes when we illuminated the chameleons in our collection with a UV lamp, and almost all species showed blue, previously invisible patterns on the head, some even over the whole body,” said David Prötzel, lead author of the new study and a Ph.D. student at the Bavarian State Collection of Zoology (ZSM).

German biologists found that the small bone bumps on chameleons’ heads fluoresce under UV light in a blueish shade. These tiny bone structures absorb UV radiation through small “windows” in the skin and then emit a soft blue light. Actually, the windows are just metaphorical, because the thin epidermis layer that covers the projections is transparent.

After seeing their shimmer under UV-lighting, scientists performed microCT scans and matched the small bone tuberosities to the blue colored pattern.

The fact that bones fluoresce under UV conditions was long-known. But using this phenomenon to intentionally fluoresce different body parts surprised the authors, as it was the first time scientists had encountered such a feature.

Okay, okay, but what’s the deal with all this effort to display such a multitude of colors, even fluorescence?

The myth that chameleons use color-change as camouflage has been debunked. A new theory states that these reptiles use skin color-shifting as a way to communicate with their kin. Taking into consideration that most males from the Calumna genus have significantly more fluorescent tubercles than the females, researchers suppose that their goal is to attract mates. Blue, being a rare color in the forest, should be quite eye-catching in this regard.

The well-known panther chameleon (Furcifer pardalis) which is also popular as a pet, shows fluorescent crests on the head. (David Prötzel; ZSM/LMU)

Another interesting observation is the distribution of fluorescence among different genera of chameleons. Researchers discovered that forest-living species are more prone to exhibit glowing tubercles than species which live in open environments.

“As shorter (UV, blue) wavelengths are scattered more strongly than longer wavelengths the UV component under the diffuse irradiation in the forest shade is relatively higher compared to the direct irradiation by the sunlight,” the authors write in the journal Nature.

“Consequently, using UV reflections for communication is apparently more common in closed habitats than in open habitats, as has been shown in chameleons of the genus Bradypodion.”

Heavily armored dino might’ve used its plates as status symbols, to attract mates, intimidate rivals

Dinosaurs’ thick, bony armor plates seem custom-tailored to absorb damage and deter predators. But a new paper describing the keratin layer adorning these plates in Borealopelta markmitchelli reports their armor might have had an even more important role: helping the dinos get some action.

Image credits Royal Tyrrell Museum of Palaeontology, Drumheller, Canada.

The bone plates of armored dinosaurs were covered in a more flexible tissue made predominantly of keratin. This formed all sorts of shapes and structures, such as caps and horns. Up to now, it’s been impossible for paleontologists to say how big or varied these structures are, simply because they almost never find them preserved in fossils.

We actually very rarely get a good impression of what dinosaurs outwardly looked like from fossils. The size, shape, and overall structure of the dinos you see in museum exhibits can be reliably observed from them. But stuff like their color, the texture of their skin or scales, the color of their eyes, those are, for the most part, our imagination at work. Fossilization requires quite a fair bit of luck and time, and the process involves high pressures, temperatures, as well as some pretty aggressive chemical substitutions. So by their very nature, fossils are bad at preserving the soft bits that give organisms their distinctive flair.

Researchers at the Royal Tyrrell Museum of Palaeontology in Drumheller, Canada, however, were lucky enough to get their hands on a Borealopelta markmitchelli fossil that beautifully preserves some of these characteristics. Discovered by a Suncor Energy mining machine operator Shawn Funk at an oil sand mine north of Fort McMurray, Alberta, it preserves not only the bony armor but also much of the layer of softer, keratin-rich tissue covering it.

The team reports that the structures are very reminiscent of the growth patterns of antelope horns and other defense-and-display structures in animals today, suggesting that dinosaurs did not shy away from using their looks to get attention.

“They might have been billboards, basically, to advertise for the animal,” says Caleb Brown, a vertebrate palaentologist at the museum.

One of kind

Armored dino.

This beast had a lot of armor. Scale bar is 10 cm / 4 in.
Image credits Royal Tyrrell Museum of Palaeontology, Drumheller, Canada.

This is actually the first B. markmitchelli ever found. The animal likely lived some 110 million years ago and belonged to the nodosaur family of dinos. Measuring in at some 5,5 meters (18 feet) in length, weighing over 1,300 kg (2,800 pounds), and clad in thick bone plates, this was a tank of a beast. Fortunately for us, it found its end in an environment that swallowed it up before fully decomposing. The fossil’s exquisite condition allowed Brown and his team to measure both the bone plates and keratin caps from the animal’s snout to the hips.

They report that the flat-ish bone plates closer to the animal’s tail were covered in a thin layer of keratin-rich material, likely there to protect it from wear and tear and provide some structural rigidity. This crust of keratin, however, got much thicker towards B. markmitchelli‘s shoulders and head. It formed large ornaments which capped the bone spikes on the dinosaurs’ neck plates, and represented up to one-third in length of the tusk-like spines on its shoulders. Wherever you look on the body, the taller the bone plate’s spikes jutted out, the thicker its keratin cap on top, according to the team.

Brown says this structure is very similar to what we see in horns and antlers today, both of which are used to fend off attackers but also serve to show off to potential mates and rivals. The fact that B. markmitchelli‘s most elaborate decorations are near the front of the animal (much like modern antlers and horns) also suggests that they were used for social signaling. Two male rivals facing off, for example, would have ample opportunity to see (and be intimidated by) each other’s thickest, most lavish stretch of armor.

All in all, these characteristics suggest that B. markmitchelli‘s spikes might have evolved (at least in part) as a means of social communication, a way for them to impress mates, scare off rivals, or both. However, Brown agrees that this remains largely speculative while working from a single specimen. We’ll have to find other fossils in a similarly good condition to know for sure.

Until then, the findings will further our understanding about the patterning on dinosaurs’ armor, and how it evolved over time. Previously, Brown showed evidence of countershading camouflage in use by the species, showing just how dangerous carnivorous dinosaurs must’ve been to force such a heavily armored beast into hiding.

The paper “An Exceptionally Preserved Three-Dimensional Armored Dinosaur Reveals Insights into Coloration and Cretaceous Predator-Prey Dynamics” has been published in the journal Current Biology.

A mouse tibia that has been rendered transparent with Bone CLARITY. Credit: CalTech.

Scientists make transparent bones to study diseases like osteoporosis

Every bone in your body no older than ten years despite how old you might actually be. Just like skin, bone sheds old tissue and grows a new one from stem cells sourced from the bone marrow. Some scientists say that observing how these stem cells interact when they transform into bone tissue could lead to new treatment and drugs for diseases such as osteoporosis. Imaging stem cells inside bones, however, has always proven challenging — until now. Remarkably, American researchers recently showed how to grow intact and transparent bones.

A mouse tibia that has been rendered transparent with Bone CLARITY. Credit: CalTech.

A mouse tibia that has been rendered transparent with Bone CLARITY. Credit: CalTech.

You don’t feel like your bones are changing because the process involves a delicate interplay of cells that build new bone mass and cells that break down old bone mass. This continual remodeling cycle is controlled by stem cells called osteoprogenitors that develop into osteoblasts or osteocytes. These cells are what regulate and maintain the skeleton. This is why scientists find it crucial to understand how these stem cells behave when new bone mass is created. But this isn’t easy. Bones don’t lie but they sure don’t give up secrets easily. The stem cells are pretty rare and not evenly distributed throughout the bone.

To determine stem cell populations in the bone, researchers usually slice the bone into thin sections then extrapolate the number of stem cells. Not only does this method introduce a lot of uncertainties, the slicing also deteriorates the bone. Being able to peer inside the bone somehow is thus very desirable in the field.

A while ago, Viviana Gradinaru, assistant professor of biology and biological engineering at CalTech, helped develop a technique called CLARITY which can render soft tissue like the brain transparent. It manages this through the removal of lipids from cells which cause tissue to be opaque. Additionally, a clear hydrogel mesh is infused to provide structural support. The approach is so effective that at one point, while working as a post-doc at Stanford University, Gradinaru and colleagues were able to make all of the soft tissue inside a mouse transparent.

Now at CalTech, Gradinaru’s lab expanded the method so it works for hard tissue as well. The team first started with bones from postmortem transgenic mice which were genetically engineered to have red fluorescent stem cells so these could be more easily identified. The types of bones selected for the study were the femur and tibia, as well as some bones of the vertebral column. No bone was longer than a few centimeters, that’s for sure.

After they removed the calcium molecules from the bones which contribute to opacity, the team infused the bones with a hydrogel that locks cellular components in place and preserve the architecture of the sample. The last step involved using a detergent to flush away the lipids, leaving a transparent bone instead, as reported in Science Translational Medicine.

To image the cells inside the bones properly, a custom light-sheet microscope for fast and high-resolution visualization was employed. This instrument does not damage the fluorescent signal.

Already, the Bone CLARITY method is being used in collaboration with a biotech company to test a new drug for osteoporosis. The condition occurs when loss of bone mass leads to a high risk of fractures and affects millions of Americans yearly.

 

“Biologists are beginning to discover that bones are not just structural supports,” says Gradinaru, who also serves as the director of the Center for Molecular and Cellular Neuroscience at the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech. “For example, hormones from bone send the brain signals to regulate appetite, and studying the interface between the skull and the brain is a vital part of neuroscience. It is our hope that Bone CLARITY will help break new ground in understanding the inner workings of these important organs.”

Inactive teens make for inactive bones

Inactive teens end up with weaker bones for life, a new study finds, highlighting the importance of physical activity during teenage years.

Researchers have confirmed what pretty much every mother has been saying since forever — if you slouch as a teenager, you’ll have bad bones.

“We found that teens who are less active had weaker bones, and bone strength is critical for preventing fractures,” said Leigh Gabel, lead author and PhD candidate in orthopedics at UBC.

Gabel and her team analyzed physical activity and bone strength in 309 teenagers, girls aged 10-14 and boys aged 12-16 — a particular period that is crucial for lifelong, healthy skeletal development. They used high-resolution 3D X-ray images to compare the bone strength in kids who got less than 30 minutes of exercise a day and in those who got the recommended 60 minutes of physical activity.

X-rays. Image credits: Nevit Dilmen.

Basically, what they found is that it doesn’t really matter what they do, as long as they do something. Whether it’s playing games or swimming or just running around, it makes a big difference. Even short bursty activities generally not considered sports help, such as dancing around the house, walking the dog, or even doing chores (sorry, kids!).

“Kids who are sitting around are not loading their bones in ways that promote bone strength,” said Gabel, which is why weight-bearing activities such as running and jumping and sports like soccer, ultimate Frisbee and basketball are important.

Also, results were similar for boys and for girls — although the bone structure of the two sexes is somewhat different in terms of bone size, density, and microarchitecture, the overall trend was similar.

Being active, in any way, as a teen is important! Image credits: Ed Yourdon.

The takeaway is pretty straightforward: we need to encourage teens to be more in their day to day life. But how? Parents and teachers can help by being a good example and limiting screen time. In most cases, browsing the internet or playing computer games takes too much time and there’s no room left for physical activity. No one is suggesting forbidding said activities, but making sure that a little bit of physical activity is fitted into their program is very important.

“We need school-and community-based approaches that make it easier for children and families to be more active,” said co-author Heather McKay, a professor in orthopedics and family practice at UBC and the Centre for Hip Health and Mobility.

“The bottom line is that children and youth need to step away from their screens and move to build the foundation for lifelong bone health,” said McKay.

Journal Reference: Leigh Gabel, Heather M Macdonald, Lindsay Nettlefold, Heather A McKay — Physical Activity, Sedentary Time, and Bone Strength From Childhood to Early Adulthood: A Mixed Longitudinal HR-pQCT study

The section of a human spine made from the new 3-D printed material. Credit: Adam E. Jakus

Reconstructive surgery gets a much needed upgrade with 3-D printed ‘hyper-elastic bones’

The section of a human spine made from the new 3-D printed material. Credit: Adam E. Jakus

The section of a human spine made from the new 3-D printed material. Credit: Adam E. Jakus

Damaged bones are some of the most challenging body parts for doctors to repair or replace. Patients who need bone grafts require these to be biocompatible, but also match the tensile strength, stiffness, and elasticity of their lost bones. Northwestern University researchers think found an elegant solution to this complex medical intervention: 3-D print new artificial bones. The team found just the right mix of materials that enables their so-called ‘hyper-elastic bones’ to not only fit perfectly because these are custom tailored, but also safely and comfortably.

[ALSO SEE] The pen that 3-D prints bone on site

The new hyper-elastic bone is mostly made of hydroxyapatite, a naturally occurring mineral packed with calcium and phosphate. Reconstructive surgery has been using this material as scaffolds implanted under the skin to promote bone growth for many years, but hydroxyapatite alone is brittle and stiff which makes customization and implant surgeries challenging.

That’s why Northwestern University researchers made a composite material that not only includes hydroxyapatite (90% weight/weight), but also other substances like collagen which is soft. The resulting composite now can withstand all sorts of forces without breaking and is flexible enough to return to its initial state.

How the 3-D printing process looks like.

Tests suggest the hyper-elastic bone can be compressed to up to 50% of its original height and still return to its original shape. Being highly porous, the material is also ideal for use as a bone graft because blood vessels can easily grow inside or on the implant.

“The first time that we actually 3D printed this material, we were very surprised to find that when we squeezed or deformed it, it bounced right back to its original shape,” Ramille Shah, one of the study’s authors and an assistant professor of materials science at Northwestern University, said during a press call.

Shah and colleagues performed a range of experiments to test their 3-D printed bone. In one test, they placed human stem cells into various scaffolds 3-D printed using the hyperelastic bone material. They found the cells grew without difficulty, filling all the available space in the material’s pores within weeks and later started to produce their own bone minerals. Typically, this process takes two to three times as much time.

In tests made on rats, the 3-D printed implant sped up spinal fusion. When working with macaque monkeys which had skull birth defects, the researchers saw bone regrowth start in only four weeks. This prompted Shah to claim that their composite material might become useful for those born with craniofacial birth defects, besides typical broken bone procedures.

To round things up, this hyper-elastic artificial bone is cheap, easy and fast to make, and can be stored without degrading for at least one year. ]

“HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors,” the researchers conclude in their paper published in the journal Science Translational Medicine.

 

 

 

Scientists use embryonic stem cells to create bone, heart muscle in just 5 days

Researchers from Stanford University have quickly and efficiently created pure populations of 12 different cell types – including bone, heart muscle and cartilage – from ancestral embryonic stem cells.

Image credit Pixabay

Image credit Pixabay

Stem cells of these cell types have been created in the past, but the current study marks the first time that pure populations have been created in a matter of days as opposed to weeks or months. In addition, previous techniques typically led to impure mixtures that contained multiple cell types, limiting their practical use.

“Regenerative medicine relies on the ability to turn pluripotent human stem cells into specialized tissue stem cells that can engraft and function in patients,” said Irving Weissman, the director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. “It took us years to be able to isolate blood-forming and brain-forming stem cells.”

“Here we used our knowledge of the developmental biology of many other animal models to provide the positive and negative signaling factors to guide the developmental choices of these tissue and organ stem cells,” he added. “Within five to nine days we can generate virtually all the pure cell populations that we need.”

Embryonic stem cells are pluripotent, meaning they have the ability to form into any cell type in the body. This process is guided by various time- and location-specific cues that occur within the embryo, ultimately pushing their development in the direction of a specific cell type. Scientists understand a lot about how this process is guided in animals such as fish, mice, and frogs, but due to the restrictions on human embryo cultivation, they know little about human embryonic development.

In the new study, the team learned that human stem cells move down a developmental path that is composed of a series of choices that present just two possible options. They found that the best way to guide these cells towards a particular fate was to encourage the differentiation into one lineage and at the same time block the other pathway. In other words, saying “yes” to one choice while simultaneously saying “no” to the other.

“We learned during this process that it is equally important to understand how unwanted cell types develop and find a way to block that process while encouraging the developmental path we do want,” said Kyle Loh, co-lead author of the study, which was published July 14 in the journal Cell.

Through careful guidance of the developmental pathway, Loh and the team were able to push stem cell differentiation in the direction that they wanted, leading to the creation of 12 different cell lineages in a quick and effective manner.

“Next, we’d like to show that these different human progenitor cells can regenerate their respective tissues and perhaps even ameliorate disease in animal models,” he said.

Oldest most complete skeleton found in the New World

In what is quite an exciting study, a mixed team of researchers and cave divers announced the discovery of a near-complete early American human skeleton with an intact cranium and preserved DNA.

Credit: Paul Nicklen/National Geographic.

Over 40 meters (130 feet) below sea level, in the Hoyo Negro area in Mexico’s Yucatan Peninsula, there lies an intricate cave system which was once above the sea. There, the divers found not only the bones from a teenage female, but also bones from extinct animals.

“These discoveries are extremely significant,” said Pilar Luna, INAH’s director of underwater archaeology. “Not only do they shed light on the origins of modern Americans, they clearly demonstrate the paleontological potential of the Yucatán Peninsula and the importance of conserving Mexico’s unique heritage.”

Indeed, the discoveries are significant on many levels. First of all, finding paleontological and anthropological remains in underwater caves is always quite interesting – definitely not something you do every day. Second of all, this is the first time researchers have been able to match a skeleton with an early American (or Paleoamerican) skull and facial characteristics with DNA linked to the hunter-gatherers which inhabited Asia some 20.000 years ago (they started to move towards the Americas some 17.000 years ago). This is also one of the oldest skeletons ever found in the Americas, and it is clearly the most complete skeleton older than 12,000 years, including preserved DNA and almost all the body parts

According to the paper’s lead author, James Chatters of Applied Paleoscience:

“This expedition produced some of the most compelling evidence to date of a link between Paleoamericans, the first people to inhabit the Americas after the most recent ice age, and modern Native Americans. What this suggests is that the differences between the two are the result of in situ evolution rather than separate migrations from distinct Old World homelands.”

The conditions in which the findings were made were extremely difficult, which is why archaeologists and anthropologists had to collaborate with professional divers in what is a laudable multidisciplinary work. The effort made by the divers is complex and difficult as the one made by researchers.

Alberto Nava with Bay Area Underwater Explorers explains:

“We had no idea what we might find when we initially entered the cave, which is the allure of cave diving,” said Nava. “Needless to say, I am incredibly proud to be part of the efforts to share Hoyo Negro’s story with the world.”

 

biopatch_bone_Growth

Biopatch stimulates bone growth via DNA instructions

biopatch_bone_Growth

(c) University of Iowa

You’ll be pretty impressed by this novel research. Scientists at  University of Iowa have developed an ingenious biopatch which expels nanoparticles containing DNA that instructs cells to turn into bone. Practically, you just apply this patch over a damaged area that needs reconstruction, dental surgery site or congenital bone defect and the genes do the rest of the job. Tests so far have only been made on mice, yet many more advances relating to efficiency and biocompatibility need to be confirmed before human clinical trials may begin.

Here’s how it works: first, the researchers build a collagen platform or scaffold, if you will. Then this scaffold is filled  with synthetically created plasmids (small independent DNA molecules), each of which is outfitted with the genetic instructions for producing bone in vivo. Theses scaffolds were inserted  over a 5-millimeter by 2-millimeter missing area of skull in test animals. Four weeks later, the team compared the bio patch’s effectiveness to inserting a scaffold with no plasmids or taking no action at all.

Collagen scaffolds embedded with plasmid DNA growth-factor complexes. University of Iowa

Collagen scaffolds embedded with plasmid DNA growth-factor complexes. University of Iowa

The plasmid-seeded bio patch grew 44-times more bone and soft tissue in the affected area than with the scaffold alone, and the patch was 14-fold higher than the affected area with no manipulation.

“We delivered the DNA to the cells, so that the cells produce the protein and that’s how the protein is generated to enhance bone regeneration,” explains  Aliasger K. Salem, Ph.D. — a professor in the College of Pharmacy. ”If you deliver just the protein, you have keep delivering it with continuous injections to maintain the dose. With our method, you get local, sustained expression over a prolonged period of time without having to give continued doses of protein.”

The researchers also point out that their delivery system is nonviral, meaning there are little chances the plasmids will generate an immune response, which would have ruined any desired treatment. If moved on to humans, the treatment could be an absolute life changer for some individuals who need implants and don’t have enough bone in the surrounding area, like the missing teeth area inside a gum for dentistry applications. Also, the procedure could be used to repair birth defects where there’s missing bone around the head or face.

Adhesion of bone marrow stromal cells (high magnification: 3500. University of Iowa

Adhesion of bone marrow stromal cells (high magnification: 3500. University of Iowa

Findings were reported in the journal  Biomaterials.