How to Repair Damaged Bones

Over the last 30 years, the scientific community has been working to develop a synthetic alternative to bone grafts for repairing diseased or damaged bone. McGill University researchers used the Canadian Light Source (CLS) at the University of Saskatchewan to advance a novel method for growing synthetic bone tissue. The rapidly advancing field of  tissue engineering is focused on growing bone  in the lab on materials called scaffolds, then transferring these structures into a person’s body to repair bone damage. Like the bone it mimics, scaffolds need an interconnected network of small and large pores that allow cells and nutrients to spread and help generate new bone tissue. The McGill team’s promising process works by modifying the internal structure of a material, called , to make it more conducive to regenerating bone tissue.

Graphene oxide is an ultrathin, extra strong compound that is being used increasingly in electronics, optics, chemistry, energy storage, and biology. One of its  is that when  are placed on it, they tend to transform into bone-generating cells called osteoblasts. The multidisciplinary group—comprising researchers from McGill‘s Departments of Mining and Materials Engineering, Electrical Engineering, and Dentistry—found that adding an emulsion of oil and water to the graphene oxide, then freezing it at two different temperatures, yielded two different sizes of pores throughout the material.Professor Marta Cerruti said that when they “seeded” the now-porous scaffolding with stem cells from mouse bone marrow, the cells multiplied and spread inside the network of pores, a promising sign the new approach could eventually be used to regenerate bone tissue in humans.

We showed that the scaffolds are completely biocompatible, that the cells are happy when you put them in there, and that they’re able to penetrate all through the scaffold and colonize the whole scaffold,” she stated.

The researchers used the BMIT-BM beamline at the CLS to visualize the different sized pores inside the scaffolding as well as the growth and spread of the cells. Lead researcher Yiwen Chen, a Ph.D. student working under Cerruti, said their work would not have been possible without the synchrotron because the low density of graphene oxide means it absorbs only a very small amount of light.

To our knowledge, this is the first time that people have used synchrotron light to see the structure of graphene oxide scaffolds,” said Chen.

Source: https://phys.org/

How to Rebuild Bone Tissue

The rapidly advancing field of  tissue engineering is focused on growing bone  in the lab on materials called scaffolds, then transferring these structures into a person’s body to repair bone damage. Like the bone it mimics, scaffolds need an interconnected network of small and large pores that allow cells and nutrients to spread and help generate new bone tissue.

The McGill team’s promising process works by modifying the internal structure of a material, called , to make it more conducive to regenerating bone tissueGraphene oxide is an ultrathin, extra strong compound that is being used increasingly in electronics, optics, chemistry, energy storage, and biology. One of its  is that when  are placed on it, they tend to transform into bone-generating cells called osteoblasts.

The multidisciplinary group—comprising researchers from McGill‘s Departments of Mining and Materials Engineering, Electrical Engineering, and Dentistry—found that adding an emulsion of oil and water to the graphene oxide, then freezing it at two different temperatures, yielded two different sizes of pores throughout the material.

Professor Marta Cerruti said that when they “seeded” the now-porous scaffolding with stem cells from mouse bone marrow, the cells multiplied and spread inside the network of pores, a promising sign the new approach could eventually be used to regenerate bone tissue in humans.

We showed that the scaffolds are completely biocompatible, that the cells are happy when you put them in there, and that they’re able to penetrate all through the scaffold and colonize the whole scaffold,” she stated.

Source: https://phys.org/

New Biomaterial Helps Bones Heal Faster

The researchers from CSI University of Medicine and Health Sciences and CHI at Temple Street (Ireland),  had previously discovered a molecule called JNK3, which is a key driver of children’s stem cells being more sensitive to their environment and regenerating better than adults’. This explains, at least partially, why children’s bones are able to heal more quickly. Building on this knowledge, they created a biomaterial that mimics the structure of bone tissue and incorporates nanoparticles that activate JNK3.

When tested in a pre-clinical model, the biomaterial quickly repaired large bone defects and reduced inflammation after a month of use. The biomaterial also proved to be safer and as effective as other drug-loaded biomaterials for bone repair whose use has been controversially associated with dangerous side-effects, including cancer, infection or off-site bone formation.

“While more testing is needed before we can begin clinical trials, these results are very promising,” said Professor Fergal O’Brien, the study’s principal investigator and RCSI’s Director of Research and Innovation.

This study has shown that understanding stem cell mechanobiology can help identify alternative therapeutic molecules for repairing large defects in bone, and potentially other body tissues. In a broader sense, this project is a great example of how growing our understanding of mechanobiology can identify new treatments that directly benefit patients – a key goal of what we do here at RCSI.”

The work was carried out by researchers from the Tissue Engineering Research Group (TERG) and SFI AMBER Centre based at RCSI in collaboration with a team from Children’s Health Ireland (CHI) at Temple Street Hospital. The CHI at Temple Street team was led by Mr Dylan Murray, a lead consultant craniofacial, plastic and reconstructive surgeon at the National Paediatric Craniofacial Centre (NPCC), who has collaborated with the RCSI team for a number of years.

It is very exciting to be part of this translational project in which the participation and consent of the patients of the NPCC at Temple Street –whom donated harvested bone cells- have contributed immensely to this success,” said Mr Murray.

The study, led by researchers from RCSI University of Medicine and Health Sciences and CHI at Temple Street (Ireland), is published in Biomaterials.

Source: https://www.rcsi.com/

Bone Tissue Just Needs A Little Bit Of Encouragement To Regenerate

Regrowing bones is no easy task, but the world’s lightest solid might make it easier to achieve. Researchers have figured out a way to use hybrid aerogels, strong but ultralight materials, to prompt new bone tissue to grow and replace lost or damaged tissue. Although bone cancer is a relatively rare disease (it accounts for less than 1% of all cancers), people who suffer from it often end up losing a lot of bone tissue and in extreme cases, undergo amputation. The cancerous tissue has to be cut out, taking with it a large chunk of nearby healthy tissue to make sure that the cancer does not spread. This effectively removes the cancer, but also leaves the patient with a lot less bone than they started out with.

A recent study has used hybrid aerogels to restore the lost tissue by prompting bone regeneration. Aerogels are basically a combination of solid and gas. Think Jell-O, but one where the water has been slowly dried out and replaced completely by air. This slow and careful removing of liquid is what allows the gel to retain its shape instead of shriveling into a hard lump. The pairing of solid and gas makes aerogels extremely light and very porous. These two qualities make them exceptionally suitable to use as scaffolds, which can be used as physical roadmaps for the developing bone to follow as it grows.

A section of bone with osteosarcoma, a type of bone cancer. This is one of the cases where lost tissue could be restored by prompting bone regeneration.

Currently, the most common methods of bone regeneration either graft new bone on to the repair site or slowly pull two bits of bone further and further apart to allow new bone to grow in the gap. If you think that these methods sound painful, complicated, and expensive, you are right.

It turns out that bone tissue just needs a little bit of encouragement to regenerate. Most of the time, simple mechanical pressure will do the trick. The fiddly bit is getting the new bone tissue to grow in the right direction and for the right amount of time. Stop it too early and the bone will be too weak to actually serve a purpose. Let it grow too much and it will end up as painful projections. This balanced growth can be achieved by using a scaffold, which is where hybrid aerogels come in. A scaffold is a structure that is placed at the site of bone repair, where it guides the growing tissue along its destined path. A good scaffold is strong but not too stiff, lasts just long enough for fresh tissue to develop, and has a lot of pores for the growing bone to snake through. This last bit is what makes a scaffold very similar to real bone. Hybrid aerogels happen to be a magic material that hits all these notes.

There are a lot of different kinds of scaffolds to choose from, ranging from ceramic and metals to cellulose hydrogels. So what makes hybrid aerogels any better than other scaffolds? For one, they are half made of proteins (that’s the “hybrid” bit), which are eventually broken down by the body. The other half, silica, slowly melts away as orthosilicic acid, which is known to hasten wound healing. Their pore size can be controlled during the manufacturing process, making it easy to adapt them to different uses. They are also being tested as drug delivery systems, meaning that the material could be spiked with medicines or growth factors before using it as a scaffold.

Earlier this year, three research labs based out of Iran, Germany, and Austria got together and decided to fuse a very strong protein with a very light and porous aerogel. The very strong protein is silk fibroin, the stuff found in silkworm cocoons and used to make fancy fabrics. It makes the aerogel strong and just stiff enough to use for bone growth. With the raw materials ready, the scientists started with Phase I: make the hybrid aerogel. Throw a source of silica, silk fibroin, some acid and a touch of detergent into a pot. Bake for an hour and voilà! You have yourself a silica-silk fibroin hybrid aerogel.

 Hybrid aerogels are strong but ultralight materials. Here, the flower is protected from the fire by the insulating properties of the aerogel
The researchers made the perfect hybrid aerogel – hydrophilic (water-loving), not too stiff, and adequately biodegradable.

Having made the material, they now moved to Phase II: check if the hybrid aerogels are in any way harmful to human cells. In fact, the cells seemed to really like the material. When the hybrid aerogel was placed in a dish containing bone cells, they readily grew on its surface, depositing the proteins and minerals required for bone growth along the way.

On to Phase III: implant the hybrid aerogel in mice and check if it stimulates bone regeneration. The researchers made small bone injuries in two groups of mice and implanted the hybrid aerogel in one of them. After 25 days, they saw that the mice with the implants showed faster and better healing than the mice without implants. The aerogel was not just allowing new bone to grow, but also making it grow faster than normal.

This ability of the hybrid aerogel to speed up bone regeneration places it on the forefront of new therapeutic technologies. Imagine having bone fractures healing in a span of days, as opposed to weeks. Or being able to tell a bone cancer patient that, “Yes, you have to cut out a section of their leg but it can be easily grown back, no worries.” Hybrid aerogels are possibly the biomaterial that could make such conversations a reality.

Source: https://massivesci.com/