Abstract
Heparin is widely recognized for its potent anticoagulating effects, but has an additional wide range of biological properties due to its high negative charge and heterogeneous molecular structure. This heterogeneity has been one of the factors in motivating the exploration of functional analogues with a more predictable modification pattern and monosaccharide sequence, that can aid in elucidating structure-function relationships and further be structurally customized to fine-tune physical and biological properties toward novel therapeutic applications and biomaterials. Alginates have been of great interest in biomedicine due to their inherent biocompatibility, gentle gelling conditions, and structural versatility from chemo-enzymatic engineering, but display limited interactions with cells and biomolecules that are characteristic of heparin and the other glycosaminoglycans (GAGs) of the extracellular environment. Here, we review the chemistry and physical and biological properties of sulfated alginates as structural and functional heparin analogues, and discuss how they may be utilized in applications where the use of heparin and other sulfated GAGs is challenging and limited.
Highlights
Glycosaminoglycans (GAGs) are a group of negatively charged linear polysaccharides found in virtually all animal tissues
To the study by Huang, SA was found to increase the activated partial thrombosis time (APTT) compared to the saline control and the non-sulfated alginates, whereas a two- and eight-fold greater effect was observed for LMWH and heparin, respectively, at similar concentrations [61]
From the present status of knowledge, sulfated alginates show in particular promise for cell immobilization and tissue engineering applications, as presented through the works of Zenobi-Wong and Cohen with their respective groups
Summary
Glycosaminoglycans (GAGs) are a group of negatively charged linear polysaccharides found in virtually all animal tissues. While structurally related to heparan sulfate (HS), heparin undergoes a greater degree of enzymatic modification during synthesis, resulting in highly diverse biological activities. An additional aspect regarding widespread use of heparin is concerns regarding safety and sustainability in its production, as the most widely used derivatives of heparin are isolated from animal tissues [1]. For these reasons, over the last few decades numerous heparin derivatives and analogues from natural sources, chemical synthesis, and chemical and/or enzymatic functionalization of polysaccharides have been described [2,3,4,5]. We further wish to discuss future directions of this research, as well as areas of application where sulfated alginates can potentially provide a viable alternative to heparin or other sulfated GAGs and derivatives
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