An alternative treatment to traditional root canals can regenerate lost tooth pulp

Each year, dentists in the United States perform more than 15 million root canals on affected teeth, removing the inflamed pulp and filling the emptied canal with inert materials such as rubber and cement. What remains is a metal casing in place of the living tooth.

Teeth that lack dental pulp are more susceptible to cracking and can respond poorly to bacterial infections and mechanical injuries in the future. In particular, we prefer to avoid killing and removing a child’s still-developing permanent teeth, but instead help the roots to thicken and lengthen.”


Vivek Kumar, bioengineer at NJIT

Supported by a $3 million grant from the National Institutes of Health, Principal Investigator Kumar, and co-investigators Amy Shimizu and Karla Kugeni at Rutgers College of Dentistry proposed an alternative treatment: restoring lost tissue in a dental cavity by inducing the body to regenerate it. Their goal is to develop a substance-based treatment that does not contain live cells and can therefore be sold on the market. It will be the first of its kind.

The team created an injectable hydrogel designed to recruit an individual’s dental pulp stem cells directly into the cleaned cavity after a root canal. The hydrogel consists of biocompatible amino acid peptides that assemble into fibres, and delivers biological signals to guide tissue growth, as well as a scaffold structure to support it.

There are currently no FDA approved technologies that can successfully restore the original dental pulp.

A procedure known as overuse of appliances is performed on immature permanent baby teeth with a carious pulp, which results in new root growth that is still forming by triggering the healing response. Tissue outside the emptied canal, when punctured, forms blood clots that secrete a protein called growth factor that sends signals to cells to produce new tissue to support the root. While some grow back, Shimizu, an endodontist who specializes in tissue regeneration, said that it is disorganized, lacking the necessary differentiation of tissues — including neurons — and fails to mimic soft tissue.

By contrast, the team’s hydrogel treatment mimics the body’s growth factor signaling and, in combination with known antimicrobial mechanisms engineered into those materials, is able to promote tissue healing and regeneration.

In early animal clinical trials, dogs injected with the team’s hydrogels formed soft tissue from the apex of the tooth to the crown in just under a month.

“We saw a lot of different tissues, including blood vessels, nerve bundles, and pulp-like cells,” Kumar said, adding that “one of the primary goals of this project is to identify the type of cells that reorganize and reconstruct regenerative tissues.”

A primary challenge for tissue engineers is angiogenesis, the plumbing that provides nutrients to regenerating cells.

To address the problem, the team’s hydrogel contains a protein known as vascular endothelial growth factor that stimulates the growth of new blood vessels, Shimizu noted.

Kojenni, a microbiologist who studies oral microbial biofilms, is focusing on another critical component of treatment: inhibiting harmful bacterial growth in new tissue.

“Even in healthy oral microbial communities, the species that can cause disease, pathogens, are usually at low levels. When they increase in numbers, a healthy microbiome can convert to pathogens. Depending on the oral disease, different species multiply,” said Cugéni. .

She noted that a peptide previously developed by Kumar for various anti-infective application was able to destroy P. aeruginosa by disrupting its membrane, adding: “We will look at a panel of oral bacteria to determine if this antimicrobial peptide hydrogel, known as K6, is effective against them.” We feel confident that it will not disrupt the entire microbiome, because our local delivery to the channel space and hydrogel properties ensure that the peptide stays where we put it.”

In a separate study, the group tested a different hydrogel containing only the antimicrobial peptide. The results showed that in combination with peptides that stimulate vascular growth, they were able to create scaffolds that perform both essential functions. Going forward, they plan to combine and test both treatments into one hydrogel.

Kumar has developed hydrogels for a number of therapeutic applications. Its delivery mechanism is customizable and consists of strands of Lego-like peptides with a biological agent attached at one end that can remain in the body for weeks and even months, as other vital substances rapidly degrade. Its self-assembling bonds are designed to be stronger than dispersed body forces; It forms stable fibers, with no signs of inflammation, which rapidly fuse into specific tissues and collagen, recruiting the original cells to infiltrate.

The hydrogel, which is also composed of amino acids, is designed to trigger different biological responses depending on the attached payload. These platforms can deliver medicines and other small merchandise over days, weeks or months. Kumar’s lab has published research on applications ranging from treatments to encouraging or preventing the creation of new blood vessel networks, to reducing inflammation and fighting microbes.

source:

New Jersey Institute of Technology

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