The “onion net” mechanics behind wound repair key to fibrosis, organ failure, says IBBME researcher

A new study published in the Journal of Cell Biology by the University of Toronto’s Faculty of Dentistry Research Institute has uncovered one of the mechanisms responsible for organ failure. Surprisingly, the body’s own natural responses to wounds are responsible for this condition – and may be the key to stopping or even potentially reversing organ damage leading to failure.

According to experts in the U.S., approximately 40-45% of all deaths can be attributed to a condition called fibrosis, a state in which cells in the body don’t recognize when to stop healing damaged tissue. This overactive response leads to scar tissue, which can overwhelm healthy tissue to the point of causing severe organ dysfunction or failure.

Professor Boris Hinz, a member of the Faculty of Dentistry’s cutting-edge research team the Matrix Dynamics Group, focused on the body’s natural to ability to repair damaged tissue. By studying the mechanical processes at work in this wound repair, Hinz was able to uncover a unique culprit behind overactive wound repair.

When tissue is initially wounded, the cells surrounding the injured site secrete a weak substance, extracellular matrix, to block the wound and patch up the damage. But eventually, the wound and the body’s response to the injury cause the cells around the damaged tissue to stretch the matrix.

“Think of an onion net,” explains Hinz. “When you put the bag down the net relaxes and everything is in normal shape. But if you pick it up the weight of the onions will straighten the net and you can’t see the mesh holes any longer. This is what our repair cells are doing. They pick on the net and straighten it over time.”

Once the cells have stretched the matrix “net” to the limit, a dormant key player in wound repair is triggered – a protein called transforming growth factor beta one (TGF-β1). “TGF-β1 released from the matrix turns weak cells into stronger cells, so the body can now create more resistant matrix,” describes Hinz. If TGF-β1 release is not controlled, though, the repair response can become indefinite, leading to fibrotic scar tissue that continuously stiffens the organs, ultimately leading to failure.

The findings, recently gracing the cover of the Journal of Cell Biology, will help researchers create targeted therapies for ending – and potentially even reversing – fibrosis by controlling the release of TGF-β1 through manipulating the mechanical strain exerted by cells.

But one strategy, Hinz stresses, will likely not be enough. “I expect that we will need a multiple drug strategy to really be effective,” argues Hinz.

Still, the discovery represents a significant leap forward in understanding not only wound repair, but the similar physiology of tumors.

“What Dr. Hinz’s work does is it links the mechanical and chemical signals together into a common approach,” adds Professor Chris McCulloch, Canada Research Chair in Matrix Dynamics in the Faculty of Dentistry’s Dental Research Institute. “This helps determine how various diseases, particularly chronic diseases such as lung and heart disease, occur in humans.”

“If you know if something works in general terms, you can use that knowledge to develop new strategies,” argues Hinz, who hopes to further his research into the reactions between cells, their matrix, and the growth factor.