Grant Supports Search for Skin Fibrosis Treatments
Can medicines reverse or stop fibrosis resulting from too much collagen?
A grant of more than $400,000 has been awarded to a researcher who is searching for new ways to treat scleroderma, how the disease begins and progresses in the skin, and how it responds to treatments.
The awardee is Karin Wuertz-Kozak, PhD, a professor in the biomedical engineering department at Rochester Institute of Technology in New York.
Wuertz-Kozak’s team will use the money granted by the U.S. Department of Defense’s Congressionally Directed Medical Research Program (CDMRP) to build on previous lab work of three-dimensional skin models, which they now will use for research in scleroderma.
“Our research will lay the groundwork to better understand the molecular mechanisms underlying the development and progression of scleroderma,” Wuertz-Kozak said in a press release. “This could be a way to realize improvements in the care and quality of life of those affected by scleroderma-induced skin alterations.”
Scleroderma occurs when the body’s immune system mistakenly attacks the connective tissue, a type of tissue that builds a scaffold around other tissues to hold them in place. In scleroderma, the connective tissue makes too much of a protein called collagen, and too much collagen causes tissue hardening and fibrosis (scarring).
“Collagen is one of the most important matrix proteins in your body. And although a loss of collagen is associated with numerous diseases, overproduction of collagen also has detrimental effects, as seen during scleroderma,” said Wuertz-Kozak.
Joining Wuertz-Kozak in the three-yea project will be Benjamin Korman, MD, who is a professor of allergy/immunology and rheumatology at the University of Rochester Medical Center.
Together they’ll develop three-dimensional skin models that can simulate scleroderma and how it responds to different medicines.
This will be done using electrospinning, a technology that allows researchers to make very fine threads (fibers) that are “spun” from drops of liquid polymer. A polymer is a chemical with large molecules made of many smaller molecules of the same kind. As the fibers are laid down on a surface, they build up and mimic the natural collagen fibers.
“Using variations in this process and the selected polymers, you can create nanofibrous constructs simulating different types of tissues,” said Wuertz-Kozak. “We started doing this as a way to have a more cost effective and controllable, high-throughput system for skin testing that can be used as an alternative to animal testing.”
Because a scaffold laid down by conventional (classical) electrospinning has very small openings or pores, the team also will use cryogenic electrospinning to build a second scaffolding layer with larger pores. Cryogenic electrospinning uses ice crystals to control how large the pores in a scaffold will be.
“For our skin model, we combine classical electrospinning with cryogenic electrospinning to create bi-layered tissue constructs that simulate the dense structure of the epidermis and the more fluffy structure of the dermis,” said Wuertz-Kozak. The epidermis is the outermost layer of cells that make up the skin, whereas the dermis lies just beneath the epidermis.
But to develop skin models of fibrosis, the team will need to seed dermal cells onto the two-layer scaffold and force them to make high amounts of collagen.
They plan to do this by treating the dermal cells with transforming growth factor beta, a protein involved in fibrosis, or by exposing them to serum obtained from people with scleroderma.
In the end, what Wuertz-Kozak’s team will want to know is whether fibrosis resulting from too much collagen can be reversed or stopped in response to medicines.
“First results look really promising,” said Wuertz-Kozak.