New Tooth Engineered Coating Stronger Than Enamel

Scientists in Russia  have perfected hydroxyapatite, a material for mineralizing bones and teeth. By adding a complex of amino acids to hydroxyapatite, they were able to form a dental coating that replicates the composition and microstructure of natural enamel. Improved composition of the material repeats the features of the surface of the tooth at the molecular and structural level, and in terms of strength surpasses the natural tissue. The new method of dental restoration can be used to reduce the sensitivity of teeth in case of abrasion of enamel or to restore it after erosion or improper diet.
Hydroxyapatite is a compound that is a major component of human bones and teeth. Scientists selected a complex of polyfunctional organic and polar amino acids, including, for example, lysine, arginine, and histidine, which are important for the formation and repair of bone and muscle structures. The chosen amino acids made it possible to obtain hydroxyapatite, which is morphologically completely similar to apatite (the main component of tissues) of dental enamel. The researchers also described the conditions of the environment in which the processes of binding of hydroxyapatite to the dental tissue should occur. Only if these conditions are met it is possible to fully reproduce the structure of natural enamel.

Traditionally in dentistry, composite restorative materials are used in enamel restoration. To increase the bonding efficiency of enamel and composite, the restoration technique involves acid etching of the enamel beforehand. The etching products left behind may not always have a positive effect on the bonding of enamel and synthetic materials. To reproduce the enamel layers with biomimetic techniques, we neutralized the media and removed the etching products using calcium alkali. In this way we improved the binding of the new hydroxyapatite layers,” explains Pavel Seredin.
The formation of a mineralized layer with properties resembling those of natural hard tissue was confirmed by field emission electron and atomic force microscopy as well as by chemical imaging of surface areas using Raman microspectroscopy. The study was conducted on healthy teeth to eliminate the influence of extraneous factors on the resulting layer and to be able to compare the results with healthy teeth. Next, the researchers will tackle the challenge of repairing larger defects, which can be of varying nature from the initial stages of caries to cracks and volumetric fractures.

The joint research was conducted by scientists from the Research and Education Center “Nanomaterials and Nanotechnologies” of Ural Federal University, Voronezh State University, Voronezh State Medical University, Al-Azhar University, and the National Research Center (Egypt).

The study and experimental results are published in Results in Engineering.


New promising Cancer Treatment

The recent approval of Lumakras (Amgen, AMG 510) by the US Food and Drug Administration as a treatment for non-small cell lung cancer is a breakthrough in cancer therapy. The drug acts as an irreversible inhibitor of KRAS, a mutant protein common to many troubling tumors, including lung, pancreatic and colorectal cancers.

KRAS has been the Moby Dick of cancer therapy. Over the last forty years, its elusive nature has stymied generations of drug developers. Discovered in 1983, it was one of the very first oncogenes ever identified. An oncogene is the mutated form of a normal human gene that often lies at the very origin of many cancers. KRAS is present in 32% of non-small cell lung cancers, 40% of colorectal cancers, and 85% to 90% of pancreatic cancers.

The normal cellular KRAS protein plays a central role in healthy cells by acting as an on/off switch for cell growth. KRAS is activated by binding to guanosine triphosphate (GTP). Once activated, the KRAS protein signals the cell to grow and divide. It is turned off when it converts GTP to guanosine diphosphate (GDP). The mutation that transforms KRAS into an oncogene locks the protein into an active state, permanently bound to GTP, causing cells to grow uncontrollably.

Why has KRAS been such a difficult problem to solve? Most drugs work by binding to sites within the crevices in a protein structure. According to Victor Cee, a research scientist formerly with Amgen,

There’s almost nowhere that a drug can stick to on that protein.” After screening a subset of chemicals, the team of researchers from Amgen found one that weakly bound to the KRAS molecule resting in a shallow pocket of the protein near the GDP binding site. Structural analysis showed that entry to a deeper crevice below was blocked by a histidine residue. Eventually, they found a family of drugs that could displace the histidine, thus allowing entry to the deeper cleft. Binding to this site alters the conformation of the nearby GDP binding site, fixing the GDP in place and permanently locking KRAS in the inactivated position.