Collagen: The Oldest Scaffold for Tissue Regeneration

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.