Dr Cedric Ghevaert of the Department of Haematology is working with Professors Ruth Cameron and Serena Best of the Department of Materials Science and Metallurgy to use collagen to create a bone-like niche to grow bone marrow cells, or megakaryocytes, for the production of blood platelets from adult stem cells. In theory, this could be used to produce platelets as and when they are needed, without having to rely on blood donations.
It may not look like much to the naked eye, but collagen is remarkably strong. The most abundant protein in the animal kingdom, it gives strength and structure to skin, tendons, ligaments, smooth muscle tissue and many other parts of the body.
Through precise manipulation at a structural level, collagen can also be used as a construction material in the laboratory or clinic to help regenerate new tissue, repair damaged cartilage and bone, or aid in the development of new therapies for cardiac disease, blood disorders and cancer.
To understand these conditions better and develop new treatments, or regenerate new tissue, researchers require models that very closely mimic the complex, three-dimensional environments found in human tissue.
As a natural material, collagen is ideal for these biomimetic applications. By shaping it into porous structures, collagen acts as a ‘scaffold’ on which cells and tissue can grow in three dimensions in predetermined forms, mimicking those found in the body.
To build the scaffolds, Cameron and Best began with a solution of collagen and water and freeze it, creating ice crystals. As the collagen cannot incorporate into ice, it gathers around the edges of the crystals. When the pressure around the ice is dropped to very low levels, it converts directly from a solid to vapour, leaving the collagen structure behind. By precisely controlling how the ice crystals grow as the water freezes, the researchers are able to control the shape and properties of the resulting collagen scaffold.
By adding small groups of amino acids known as peptide sequences to the surface of the scaffold at different points, the way in which the collagen interacts with the growing cells changes, altering the potential uses for the scaffold. The peptide sequences signal certain cells to bind to the scaffold or to each other, while signalling other cells to migrate. Collectively, these signals direct the scaffold to form a certain type of tissue or have a certain type of biological response.
“The technology for culturing the cells is actually quite generic, so the range of applications it could be used for in future is quite broad,” said Best. “In terms of clinical applications, it could be used in almost any situation where you’re trying to regenerate tissue.”
“In some senses, it can be used for anything,” added Cameron. “As you start to create highly organised structures made up of many different types of cells – such as the liver or pancreas – there is an ever-increasing complexity. But the potential of this technology is huge. It could make a huge difference for researchers and patients alike.”