Bioengineering Tissue    

    Defects for collagen usually come in their molecular formation. Sometimes, the domains in collagen get the wrong types of proteins, the order gets skewed, or the wrong alpha chain might get added to a collagen type. The two primary forms of collagen defects are mutagenic defects and secondary issues, where the mutation is coming from somewhere else, but the collagen/tissue gets injured as a byproduct (for example, Alkaptonuria and Menkes syndrome) (McKusick et al., 1974). Any defect in the synthesis of the collagen can lead to a connective tissue disease (Uitto & Lichtenstein, 1976). Not all defects are bad; some irregularities are often to be expected within the repeating units, and they occasionally help formation of the triple helix, but it is largely the case that mutations are not beneficial, especially when it is glycine that is being replaced (glycine substitutions are what leads to osteogenesis imperfecta, or OI) (Shoulders & Raines, 2009). Moreover, collagen deficiencies pose huge problems in the body (Uitto & Lichtenstein, 1976; Glorieux & Rowe, 2012). 

    As for durability, as described in the structures section, the strength of collagen is somewhat dependent on its type (fibrils are much stronger than other macromolecules), but in general, the rods themselves, are not too structurally sound; the macrostructures and the orientation/alignment of the fibers is what gives collagen so much strength (although it typically requires additives to get even stronger) (Shoulders & Raines, 2009). Therefore when the macrostructures are broken down, collagen loses its strength. Collagen is particularly susceptible to UV light exposure and aging, which reduce its strength Jariashvili et al., 2012; Zayas, 1997, pp. 11-12). Also, while collagen is insoluble in water, exposure to enzymes or alkaline materials will eventually break it down, dissolve it, and make it soluble/able to be hydrolyzed (Mohammad et al., 2014; Wu et al., 1981; Bowes & Kenten, 1950). For this reason, it is very important that endothelial cells (and other cells) are able to grow properly on engineered/decellularized collagen scaffolds, as they serve as a protective layer between collagen scaffolds and bodily fluids, which forever change pH and get exposure to a multitude of enzymes/acids/alkaline materials/water.