Rebuilding Bone and Tissue, Cell by Cell

New nano-scale structures aim to speed the regeneration of bone and cartilage.

The human body doesn’t come with many spare parts.

For bones, in particular, the options available to fix large or complicated injuries, or to treat tumors and diseases, can come with problems. What little bone there is to mine from elsewhere in the body might not be sufficient to fill a large gap. And bone implants from other sources—human or animal donors, or implants fashioned from other materials—can loosen over time, wear down, transmit diseases and be rejected by the body. Repairing cartilage faces much of the same, plus the body has far less capacity to regenerate it.

Scanning electron microscopy images, at low (top) and high (bottom) resolutions, show the artificial, web-like matrix of bone scaffolding created by Dr. Zhang and her collaborators for research appearing in the International Journal of Nanomedicine. (Images courtesy Lijie Grace Zhang)

Recent studies by GW researchers are pointing toward new ways of mimicking biological processes in order to help implants better integrate into the body, and to help the body grow new bones and even cartilage where it’s needed.

“Tissue engineering is a very promising field,” said Lijie Grace Zhang, an assistant professor in the Department of Mechanical and Aerospace Engineering. “It combines engineering with life sciences to design tissue or even organ substitutes.”

At the nano level, bones are made up of a porous, web-like matrix of scaffolding—miniscule construction projects that scientists have been trying to emulate in the lab using an increasing variety of biologically-inspired nanomaterials and building tools.

In a study published this spring in the International Journal of Nanomedicine, a team led by Dr. Zhang and Michael Keidar, director of the GW Institute for Nanotechnology, tested a new design for a synthetic bone architecture.

The composite acts like a starter kit, giving the body’s bone-building cells a structure to latch on to that will slowly break down, leaving only new bone.

The new design is based, as some others have been, within a wad of spongy gel called chitosan, which is made from a material found in the hard exoskeletons of crustaceans and insects, and is biodegradable in the body.

Their design, however, used a new process for recreating the nano-sized mineral scaffolding inside bones, allowing researchers to better control its shape and size at the nano level. And, for the first time, the researchers buttressed that structure with single-walled carbon nanotubes that were created within a magnetic field.

Carbon nanotubes, well-known for their strength, flexibility and electrical conductivity, are typically around 1 nanometer in diameter—about 100,000 times smaller than the diameter of a hair. Those created in the presence of a magnet were even smaller in diameter, longer in length and had greater conductivity.

Testing various combinations of these ingredients, including carbon nanotubes formed outside of a magnetic field, the team wrote that any amount of the synthetic scaffolding paired with either type of carbon nanotube “greatly augmented” the ability of bone-forming cells, called osteoblasts, to latch onto the bone substitute.

In particular, the researchers wrote that the structure of the longer, thinner magnetically-generated nanotubes may “have a considerable effect on [the ability of carbon nanotubes] to support bone cell growth.”

And since bone growth can also be sparked by very low-voltage electrical therapy, the researchers reported that these modified nanotubes, with their higher electrical conductivity, “hold great potential for application in bone tissue engineering.”

Meantime, in research slated to be published in the Journal of Nanoscience and Nanotechnology, a team led by Dr. Zhang and Dr. Keidar found that the same materials could be used as a new type of coating on titanium-based bone implants to provide fertile ground for growing bone cells.

Similar to other bone implant coatings, the idea is to provide a bone-like surface on metal implants so they bond better with surrounding bone. The researchers found their new materials from the previous study did just that, boosting the attachment and proliferation of bone-forming osteoblasts as well as stem cells.

Dr. Zhang said the next step for both of these projects will be to focus on stem cells—unspecified cells that replenish the body by turning into specialized cells, like bone cells—and to refine the designs to act increasingly like actual bone.

For the scaffolding research, both a patient’s osteoblasts and stem cells can be “seeded” into the design, said Dr. Zhang, adding to what the body produces in hope of speeding up the process. And for both projects, the team will have to figure how to use the design and chemical environment around it to coax stem cells into bone cells.

It’s an area Dr. Zhang’s team is already exploring as it relates to cartilage, and she anticipates those results will be reported at a conference next month.

Cartilage, in part, reduces friction between bones in a joint but it doesn’t have much capacity for rebuilding itself. Dr. Zhang’s lab is studying ways to stimulate cartilage regeneration using two new types of biomimetic structures—injectable, self-assembling nanotubes that rely on the same molecules and bonding that form DNA; and nanotubes that are enmeshed in a tapestry of microfibers.

Injecting structures that can regenerate cartilage or bone, rather than an open surgical implantation, “lowers the cost of treatment, and patients can recover much faster and with significantly reduced pain,” said Dr. Zhang.

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