Abstract
AbstractSulfated polysaccharides are ubiquitous in living systems and have central roles in biological functions such as organism development, cell proliferation and differentiation, cellular communication, tissue homeostasis, and host defense. Engineered sulfated polysaccharides (ESPs) are structural derivatives not found in nature but generated through chemical and enzymatic modification of natural polysaccharides, as well as chemically synthesized oligo‐ and polysaccharides. ESPs exhibit novel and augmented biological properties compared with their unmodified counterparts, mainly through facilitating interactions with other macromolecules. These interactions are closely linked to their sulfation patterns and backbone structures, providing a means to fine‐tune biological properties and characterize structural–functional relationships by employing well‐characterized polysaccharides and strategies for regioselective modification. The following review provides a comprehensive overview of the synthesis and characterization of ESPs and of their biological properties. Through the pioneering research presented here, key emerging application areas for ESPs, which can lead to novel breakthroughs in biomedical research and clinical treatments, are highlighted.
Highlights
Natural sulfated polysaccharides are found in a large variety of living organisms and have widely diverse biological roles, depending on their molecular structure and interaction with other biomolecules
3.1.1 Effects of sulfation degree on anti-coagulating properties The importance of the sulfate groups is evident, as sulfated polysaccharides are commonly observed to prolong coagulation times compared to their non-sulfated controls, and the anti-coagulant properties of natural sulfated polysaccharides can be enhanced through over-sulfation.[115-117]For instance, oversulfation of fucans derived from brown algae resulted in an increased activated partial thromboplastin time (APTT) compared with the native sulfated fucan as well as heparin.[118]
The results show that the sulfation pattern is a more important factor than dermatan sulfate (DS) for differentiation in this specific model, and they further imply that the process by which sulfated chitosan promotes neural differentiation of embryonic stem cell (ESC) is similar to heparin/heparan sulfate (HS).[513]
Summary
Natural sulfated polysaccharides are found in a large variety of living organisms and have widely diverse biological roles, depending on their molecular structure and interaction with other biomolecules. Structural variants of heparin, CS, and HS have been identified,[3] as well as sulfated galactans and fucans with or without branching[4] in other marine invertebrates such as bivalves, echinoderms, and ascidians These GAGs are studied less than their vertebrate counterparts, their biological functions in tissue development and maintenance are presumably related.[5, 6]. The anionic nature of the sulfated polysaccharides further allows formation of electrostatic complexes toward dynamic sequestration of bioactive compounds and assembly of biomaterial structures such as hydrogels, films, or fibers for drug and cell delivery vehicles For some of these applications, native GAGs may exhibit limitations with respect to production cost, batch standardization, immunogenicity, degradability, or other aspects.
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