The research for regenerative medicine has currently focused on the development
of pluripotent cells, i.e., embryonic stem cells and induced pluripotent
cells. These cells have been proven to differentiate target cells in vitro, but they
could not reproduce an organized arrangement with other types of cells and extracellular
matrices, including collagens, elastins, proteoglycans, and others. Although
growth factors influence cells to proliferate and differentiate target cells,
most of them are unstable or diffusible in vivo. Growth factors, designed to bind to
specific extracellular matrices, have been introduced to the tissue regeneration. Fabrication
and development of three-dimensional structures are highly desired to regenerate
tissues and organs large enough for transplantation.
Collagen is the major extracellular matrix in mammals, also found in the animals belonging to the phylum
polifera, e.g., sponges, and distributed in the jelly-like mesophyl between two thin cell layers.
Therefore, collagen is the oldest extracellular matrix providing a scaffold for cells in multicellular organisms.
Collagen is a protein family consisting of 28 different types, which polymerize into fibrils or
basement membranes. By fabricating graded structures specific for target tissues and organs, one can
obtain suitable scaffolds for tissue regeneration. Decellularized scaffolds would presently be one of the
best options because they can maintain the basic architecture of extracellular matrices such as tissue
size. In this review, the origin, polymerized structure, and graded arrangement of collagen in extracellular
space will be discussed. Some examples of a bioreactor to regenerate the tissue constructs together
with collagen and cells are also presented.