**5. Dermatan Sulfate**

DS is found in the cornea, where it maintains optical clarity, and in the sclera, where it helps to maintain the eye's overall shape [93]. Further, it is found in blood vessel walls, heart valves, and the umbilical cord during pregnancy where it plays a key role in regulation of the extracellular matrix [93]. Its composition is very similar to that of CS, as demonstrated by its former name CS type B, however I-iduronic acid a C5 epimer of glucuronic acid, substitutes for hexuronic acid found in CS [50]. Sulfation is found on C4 or C6 of the galactosamine ring and sulfation levels increase with age [93].

DS has been implicated in the development of many pathologies, such as cancer metastasis [94], connective tissue diseases [95], and inhibited neuron regeneration [96]. Research focusing on DS in tissue engineering is sparse, with the bulk of research focusing on discovery of its functions and some research focusing on DS, modified DS, and DS proteoglycans as therapeutics or as a targeting mechanism for drug delivery [97–101]. This lack of exploration can likely be attributed to two key factors: the recent reclassification of DS from chondroitin sulfate B, and the extreme complexity of DS synthesis and physiological interactions. DS interactions are based upon the composition and sulfate functionalization patterns of the chain allowing for a high diversity of patterns and potential interactions similar to those seen for CS. For example, xyloside-primed dermatan sulfate from breast carcinoma cells has cytotoxic effects and this behavior is only exhibited by DS of a defined disaccharide composition [102]. This is the first example of cytotoxic effects of dermatan sulfate and highlights the complexity of cell interactions with sulfated GAGs. There has, however, been some research focusing on the use of DS in tissue engineering. DS proteoglycans are key moderators of fibrinogenesis and K.M., et al. have shown that this behavior can be recapitulated in vitro when combining DS with collagen scaffolds. Collagen fibril formation was shown to be dependent on DS concentration, with low concentrations resulting in disorganized fibrils and higher concentrations resulting in more organized, but less dense fibrils [103]. A more unique use for DS in tissue engineering may be in surface modification of implantable devices. DS, when combined with chitosan in a multi-layer coating on polyethylene terephthalate surface show high surface wettability and inhibited biofilm formation, two important factors in implantable devices such as vascular prosthetics [104].

It has also been shown recently that mouse embryonic stem cells undergo neuronal differentiation via activation of signal-regulated kinase 1/2 and human neural stem cells undergo neuronal differentiation and neuronal migration in the presence of DS [105]. This lends some promise to the use of DS to drive stem cell differentiation in neuronal tissue engineering constructs similar to the use of HA and CS as mentioned previously.
