Study Shows How Drugs Developed to Treat Periodontal Disease Impact Blood Vessel Elasticity

It’s preventable with proper dental care and oral hygiene—regular brushing, interdental cleaning, and the use of antimicrobials such as chlorhexidine—yet periodontal diseases negatively impact half of all American adults. In fact, the most recent statistics from the United States Centers for Disease Control and Prevention indicate that nearly half of adults ages 30 years and older suffer from some type of periodontal disease.¹ 

And the disease progresses with age, leaving more than 70% of adults 65 years and older afflicted. Such numbers have the scientific community on the lookout for new strategies to remedy this severe but all too common form of oral disease.¹

EFFECTS OF PRESSURE

Researchers from the American Dental Association Science and Research Institute (ADASRI) and the National Institute of Standards and Technology recently joined forces to better understand how fluid flow through blood vessels affects the mechanical properties, including elasticity and permeability, of biological tissue under pressure. Such information could prove beneficial in uncovering new periodontal treatment avenues.^2,3

The researchers observed how constant flow and pressure from hemodynamic forces affect microvascular structures in the body, allowing the exchange of waste and nutrients. But when hydrostatic pressure in the oral mucosa or bone is elevated, the microvascular membrane becomes more permeable, allowing movement of molecules from the bloodstream to the interstitium. This can lead to edema, the accumulation of excess interstitial fluid, and damage of the surrounding tissue.³

PRINTING BIOLOGY

Because of the drawbacks of in vivo and two-dimensional in vitro studies cited by the researchers, they employed three-dimensional (3D) printing to create a 3D microvascular platform to measure the elasticity and membrane permeability of the endothelial cell layer in vitro. 

The printed model comprised microfluidic chambers containing channels that were designed to allow the flow of small amounts of fluid under hydrostatic pressure via a pneumatic pressure controller. Varying degrees of pressure-induced deformation were measured by tracking the mean vessel diameter.³

Human endothelial cells were introduced into the collagen-infused channels, followed by a growth medium. These adhered to the channel walls, forming artificial blood vessels approximating the size of large capillaries and thickness of endothelial cells.³

TRACKING THE FLOW

Fluorescent dye was pushed through the channels to chart its flow through cell layers to determine membrane flow resistance under applied pressure. Its flow, tracked with a 3D confocal microscope, revealed possible leakage of fluid particles through the cell layer or entrapment of the fluid in small pores. Additionally, 3D positions of cell nuclei were also tracked while under pressure so researchers could observe any deformation, which did occur. In fact, they write that the largest deformations correlated with local porosity.^2,3

The researchers speculate that the study may enhance understanding of how drugs affect blood vessels, how tissue resists inflammation, how capillaries regulate blood pressure, and how tissue acts as a protective physical barrier. They note that the 3D approach offers a viable in vitro option for investigating microvascular-related diseases.^2,3

Says ADASRI’s Stella (Styliani) Alimperti, PhD, a project leader on the study, “In the future, we could use these microfluidic chambers to study the way experimental drugs for treating periodontal disease affect the elasticity of blood vessels.”²

REFERENCES

1. United States Centers for Disease Control and Prevention. Periodontal Disease. 
2. Versaci MB. ADASRI collaborates with NIST to create artificial blood vessels to study effects of fluid flow on tissue. ADA News.

3. Salipante PF, Hudson SD, Alimperti S. Blood vessel-on-a-chip examines the biomechanics of microvasculature. Soft Matter.