Fucoidans are multifunctional marine macromolecules that are subjected to numerous and various downstream processes during their production. These processes were considered the most important abiotic factors affecting fucoidan chemical skeletons, quality, physicochemical properties, biological properties and industrial applications. Since a universal protocol for fucoidans production has not been established yet, all the currently used processes were presented and justified. The current article complements our previous articles in the fucoidans field, provides an updated overview regarding the different downstream processes, including pre-treatment, extraction, purification and enzymatic modification processes, and shows the recent non-traditional applications of fucoidans in relation to their characters.
of 22reproductive, immune and cell-to-cell communicative roles [23]. As recommended by the International Union of Pure and Applied Chemistry (IUPAC), fucoidans is a general term used to describe sulfated L-fucose-based polymers including sulfated fucans cited by the Swedish scholar Kylin, as well as other fucose-rich sulfated heteropolysaccharides [23,28]. Their chemical structures, in terms of monomeric composition and branching, are quite simple in marine invertebrates compared to their analogues in brown algae [13,29].Hundreds of articles have thoroughly discussed and reviewed the biological, pharmacological and pharmaceutical applications of fucoidans [30][31][32][33], including nanomedicine, [34] which has made it a hot topic in the last few decades [35][36][37]. All these studies tried to investigate fucoidans molecular mechanisms in relation to their chemical structure and physicochemical properties. Therefore, different hypotheses were suggested for each activity, such as anti-tumor [31,[38][39][40], anti-coagulant [41,42], anti-viral [43,44] and anti-inflammatory activity [45,46]. These investigations revealed that various factors are relevant, such as molecular weight, sulfation pattern, sulfate content and monomeric composition [47][48][49]. For example, different fractions were produced with different physicochemical properties in our previous experiments; sulfation pattern and sulfate content were highly related to anti-viral and cytotoxic activities against HSV-1 and Caco-2 cell lines, respectively, while molecular weight and sugar composition were potential factors in anti-coagulation activity [41,50]. In addition, degree of purity was reported as an influential factor [32], where co-extracted contaminants (e.g., phlorotannins or polyphenols) could lead to significant interference in anti-oxidant activity and, consequently, cosmetic applications [51,52].Therefore, several key production challenges regarding fucoidans were discussed in our last review article in order to obtain a product that follows the universal good manufactured practice (GMP) guidelines. The article discussed sources of heterogeneity in extracted fucoidans, including the different biotic (e.g., biogenic, geographical and seas...