Every year, U.S. dentists perform more than 15 million root canals on infected teeth, removing inflamed pulp and filling the empty canal with inert materials such as rubber and cement. What is left is a mineral shell instead of a living tooth.
Teeth that do not have dental pulp are more vulnerable to breakage and may respond poorly to future bacterial infections and mechanical injuries. In particular, we prefer to avoid killing and removing the permanent tooth of a child who is still growing, but instead to help the roots thicken and lengthen. “
Vivek Kumar, bioengineer at NJIT
With the support of a $ 3 million grant from the National Institutes of Health, Kumar, the principal investigator, and co-researchers Emi Shimizu and Carla Cugini of the Rutgers School of Dental Medicine have proposed an alternative remedy: restoring tissue lost in the dental cavity by inducing the body to regenerate it. Its aim is to develop a material-based therapy that does not contain living cells and can therefore be sold commercially. It would be the first of its kind.
The team has created an injectable hydrogel designed to recruit stem cells from a person’s dental pulp directly into the disinfected cavity after a root canal. Composed of biocompatible amino acid peptides that aggregate into fibers, the hydrogel provides biological clues to direct tissue growth, as well as a scaffolding structure to support it.
There are currently no FDA-approved technologies that successfully restore native dental pulp.
A procedure known as over-instrumentation is performed on the immature permanent teeth of children with necrotic pulp, causing a new root growth still in formation causing a healing response. Tissue outside the emptied canal, when punctured, forms blood clots that secrete a protein called growth factor that tells cells to produce new tissue to support the root. Although some grow, they are disorganized, do not have the necessary tissue differentiation, including nerve cells, and fail to mimic soft tissues, said Shimizu, an endodontist who specializes in tissue regeneration.
In contrast, the team’s hydrogel therapy mimics the body’s own growth factor signaling and, along with the known antimicrobial mechanisms designed in these materials, is able to promote tissue healing and regeneration.
In the first animal clinical trials, the team’s hydrogel-injected dogs 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, “One of the main goals of this project is to determine the type of cells they reorganize. and repopulate the regenerated tissue. “
One of the main challenges facing tissue engineers is to create blood vessels, the plumbing that provides nutrients to regenerated 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.
Cugini, a microbiologist who studies oral microbial biofilms, focuses on another critical component of therapy: inhibiting harmful bacterial growth in new tissue.
“Even in healthy oral microbial communities, the species that can cause disease, the pathobionts, are usually at low levels. When they increase in number, a healthy microbiome can turn into a pathogenic one. Depending on the oral disease, different species proliferate. “. said Cugini.
He noted that a peptide that Kumar previously developed for a different anti-infective application could destroy the P. aeruginosa germ by disrupting its membrane, adding: “Let’s look at a panel of oral bacteria to determine if this antimicrobial peptide hydrogel. “We know it won’t disturb the whole microbiome, because our localized 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 that contained only the antimicrobial peptide. The results showed that, in combination with peptides that stimulate the development of blood vessels, it was able to create scaffolds that performed both critical functions. In the future, they plan to combine and test both therapies in a single hydrogel.
Kumar has developed hydrogels for various therapeutic applications. Its delivery mechanism is customizable and consists of Lego-like peptide chains with a biological agent attached at one end that can survive in the body for weeks and even months, where other biomaterials degrade rapidly. Their self-assembling bonds are designed to be stronger than the dispersive forces of the body; it forms stable fibers, with no signs of inflammation, which are rapidly incorporated into specific tissues and collagen, recruiting native cells to infiltrate.
Hydrogel, which is also composed of amino acids, is designed to trigger different biological responses depending on the payload attached. These platforms can deliver drugs and other small loads for days, weeks or months. Kumar’s lab has published research on applications ranging from therapies to cause or prevent the creation of new blood vessel networks, reduce inflammation, and fight microbes.
Source:
New Jersey Institute of Technology