# Routes towards Novel Collagen-Like Biomaterials
### Molecular Structure of Collagen  
Collagen is typically found in all animals, occurring early in evolution in several simple multicellular organisms such as sponges (_Porifrae_) [3] and _Cnidariae_[4]; however it is not present in plants and fungi, where its role has been taken over by polysaccharides such as cellulose and chitin. While it has been shown that collagen plays a crucial role in the formation of the animal extracellular matrix [5], collagen-like proteins have also been identified in several bacteria [6], where they mask the bacterial cell from animals' immune receptors and facilitate the formation of biofilms as well as the adhesion to host tissue. Not taking into account several exceptions from the rule, such as collagen-based insect silks which are spun from specialized glands [2], collagens in higher eukaryotes are generally not secreted outside the respective tissue and contribute to and often largely define its mechanical and biochemical characteristics. While several classes of collagens are fibrous, especially those abundantly found in bone, skin, tendon, cartilage and connective tissues (types I, II, III, V, XI, XXIV and XXVII) [7], most people associate collagen with gelatin (made from type I collagen). While the extraction of gelatin from collagen-rich tissues involves partial hydrolysis of the protein, as well as the partial or complete unfolding of the triple helix due to thermal denaturation, some mild extraction methods for triple helical collagen exist (see below) [8; 9]. Although based on the same polypeptide, gelatin and collagen have vastly different properties, which largely stem from the fact that mature collagen has lost its ability to self-assemble into discrete fibrils, and therefore, once the triple helix has been denatured, restructures into an amorphous gelatin network. Recent advances in both the recombinant production of synthetic collagen-like proteins and new, mild extraction and purification techniques out of natural sources, as well as the advanced processing of these extracts have opened a range of possibilities allowing the production of collagen-based materials with remarkable mechanical and biological properties. Many new methods to process collagen are biomimetic and some are inspired by the natural fiber spinning process of silk-producing animals [10; 11; 12]. Collagen fibers are hierarchically assembled structures that can be readily identified by their amino acid sequence [13]. A specific consensus sequence has been identified for collagen which follows the pattern (GXY)\({}_{n}\), with the X-position often being proline residues and the Y-position often being 4-hydroxyproline residues. On a genetic level the high glycine and proline content of collagen-encoding genes creates GC-rich patches, which makes the identification of such genes from genomic sequences difficult, so that most known collagen sequences were obtained by cross-referencing cDNA-libraries with Edman-based peptide sequencing [14; 15]. The (GXY)\({}_{n}\) consensus sequence can be explained by the spatial requirements for the formation of the triplehelical collagen tropomolecule [16]: Being a right-handed triple-helix with one turn every three amino acids and a very narrow diameter of 1.6 nm, in order for the molecule to fold, steric hindrances due to bulky amino acid side chains must be omitted on every position pointing said residue inwards, explaining the occurrence of glycine as every third residue. This glycine is essential, and mutations or deletions of the consensus motif have been shown to have a strong destabilizing effect on the collagen molecule, often described as \"nicks\" due to the localized breaking of the rigid helix and the resulting angular flexibility [17; 18].