• The Morgan lab has developed a new ring-shaped 3D microtissue model of fibrosis. Fibrosis is a disease of multiple organs including skin, liver, kidney, heart and lung where excess deposition of collagen by connective tissue cells results in scarring that severely compromises organ function.
• The ring-shaped microtissues are comprised of human fibroblasts, the cells of connective tissue that are responsible for the production of collagen as well as the other proteins that constitute the extracellular matrix (ECM).
• The ECM surrounds all cells and is largely responsible for the mechanical properties of tissues and organs. The pathological overproduction of collagen and ECM during fibrosis increases the stiffness of organs which adversely affects organ function.
• In the ring-shaped microtissue model, the human fibroblasts elongate, align and contract to form a 3D ring-shaped tissue with a histology that mimics human connective tissue. The fibroblasts synthesize abundant amounts of collagen and other ECM proteins and organize these proteins into complex fibers that encircle the ring.
• Using a mechanical testing instrument, we’ve measured the stiffness and tensile strength of the rings. We’ve shown that addition of TGF-b1, a growth factor implicated in promoting fibrosis, increases the stiffness and tensile strength of the rings. Conversely, we’ve shown that addition of the drug SB-431542 which inhibits TGF-b1 actions, decreases the stiffness and ultimate tensile strength of the rings.
• Because we can carefully measure changes to the stiffness of the ring-shaped microtissues, we now have a new model based on human cells that more closely mimics the increase in stiffness that adversely affects fibrotic organs.
• We are using ring-shaped microtissues to measure the effects of chemicals and growth factors that may promote fibrosis. And, we are using ring-shaped microtissues to measure the effects of drugs that may be useful for the treatment of fibrosis.

Wilks, B.T., Evans, E.B., Howes, A., Hopkins, C.M., Nakhla, M.N., Williams, G. & Morgan, J.R. (2022) Quantifying cell-derived changes in collagen synthesis, alignment, and mechanics in a 3D connective tissue model. Advanced Science. In press.