Tag Archives: fracture

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.

Scientists find protein that stimulates bone growth in humans

A new study conducted by US researchers has found that a protein called Jagged-1 stimulates stem cells to differentiate into bone-producing cells, possibly saving or improving the qualify of life for millions of people.

jagged1

The fact that their research was peer reviewed and accepted for publishing in the Stem Cells journal definitely backs the validity of their claims. They suggest that Jagged-1 could help both human and animal patients heal from bone fractures faster and may form the basis of treatments for a rare metabolic condition called Alagille syndrome.

Although the general image is that bones are static and permanent, the bone tissue inside our bodies is actually constantly changing and reforming throughout our lives. Cells called osteoblasts form bone and are derived from precursor cells known as mesenchymal stem cells, which are stored in bone marrow. When these cells receive the order, they transform into osteoblasts and start building up bone.

Prior research had already discovered a protein called bone morphogenic protein (BMP) that can drive stem cells to create bone cells, but there are several safety and efficiency issues with BMP. Most notably, there is the constant danger of overgrowth; once BMP starts to work its magic, it’s pretty hard to actually stop the bones from growing.

“[..]But it has become clear that BMPs have some issues with safety and efficacy. In the field we’re always searching for new ways for progenitor cells to become osteoblasts so we became interested in the Notch signaling pathway,” said senior author Prof Kurt Hankenson of the University of Pennsylvania’s School of Veterinary Medicine.

As I said previously, this could work on both animals and humans, because most animal species have this molecular signaling pathway that plays a role in stem cell differentiation; think of this as the phone line through which stem cells are told to form bone tissue. The researchers chose to investigate one of the proteins that acts in this pathway by binding to the Notch receptor called Jagged-1; previously, they had already shown that Jagged-1 is highly expressed in bone-forming cells during fracture healing.

“That had been our operating dogma for a year or two,” Prof Hankenson said.

Of course, the next step was to figure out what exactly happens when you introduce Jagged-1 to human stem cells. The result was quite surprising.

“It was remarkable to find that just putting the cells onto the Jagged-1 ligand seemed sufficient for driving the formation of bone-producing cells,” he said.

The finding is also consistent with other evidence that links Jagged-1 to bone formation. Patients with a rare disease known as Alagille syndrome frequently have mutations in the gene that codes for Jagged-1. The thing to keep in mind is that while this research offers some remarkable insight into the growth of bones, it will be a while before Jagged-1 fixes your broken foot.

Study: Fengchang Zhu et al. 2013. Pkcδ Is Required for Jagged-1 Induction of hMSC Osteogenic Differentiation. Stem Cells, accepted for publication; doi: 10.1002/stem.1353

Shorties: Adding more calcium to your diet won’t reduce fracture risk

The benefits of calcium in your diet are numerous, but according to a study conducted by University of Sweden researchers. Their study concludes that increasing calcium intake beyond a moderate amount does little to nothing in preventing osteoporosis later in life, or reduce fracture risk.

The study, published online Tuesday on the British Medical Journal website, intended to shed some light on the long standing debate of how much calcium is enough. They found that increasing consumption beyond 700 mg – equivalent to 3 oz (85 g) of sardines, bones-in and and an 8 oz pot (227 g) of yogurt has a negligible impact.