Bioengineers belonging to Rice University are working on building an experimental device using paper to study heart diseases. The team is using paper-based structures that resemble the layered nature of aortic valves, the tough, flexible tissues that maintain blood flow through the heart in a single direction. The devices allow engineers to carry out a detailed study on how calcifying diseases can slow or stop the heart from functioning. The team from Brown School of Engineering published their work in Acta Biomaterialia, describing how collagen 1, a natural protein and a component of the valves’ fibrous extracellular matrix, has a strong link with calcification when existing outside of its usual domain. Valves that are hardened by calcium deposits are less flexible and are unable to seal the heart’s chambers.
Jane Grande-Allen, a Rice bioengineer, who directed the study along with lead author Madeline Monroe, a Rice graduate, explains that fibrosis occurs when tissues produce excess type 1 collagen and can happen in various types of tissues. It accompanies calcific aortic valve disease (CAVD) that does not imply collagen will always lead to CAVD, although it did drive the calcification-associated phenotype in the cells, cultured by the team, added Grande-Allen. Collagen typically stays in the valve’s fibrosa layer, which is one of three in each of the three leaflets that constitute an aortic valve. The researchers designed paper layers to support heart valve cells that were embedded in either collagen or hyaluronan and discovered that when collagen 1 proteins are present in multiple layers, the cells can potentially cause mineralized lesions.
Grande-Allen went on to explain that the layers of extracellular matrix in a healthy aortic valve are well structured, and in a more pathological state, the collagen is not localized but scattered, and their models indicate that non-localized collagen could bring about the cell overexpression of the calcific factors. The researchers created the device aiming to see how valve cells would respond to collagen spreading through a three-dimensional tissue, and they found common filter paper to be a suitable substitute.