Agarose is the major component of agar, a polysaccharide (PS) from red algae that has been used for centuries as a traditional food gelling agent. Recently, agarose hydrogels received high interest for advanced applications such as cell encapsulation and tissue engineering because they are non-cytotoxic, show high mechanical strength, and are highly porous with a high water content ≈ 99%. However, agarose is bio-inactive and does not stimulate important cell processes such as adhesion, migration, proliferation, and stem-cell differentiation. Aim of the present work is to overcome this limitation by synthesis of well-defined agarose derivatives that are subsequently transformed into novel PS hydrogels. Two different homogeneous synthesis strategies were pursued in this context using dipolar aprotic solvents (with and without LiCl) and ionic liquids as reaction media: (i) Non-natural agarose sulfates (AS) were prepared under different reaction conditions. The derivatives showed a regioselective modification at the primary G-6 position and were either completely soluble in water or showed thermoreversible gelation depending on the degree of substitution (DSsulfate). Natural PS sulfates and materials derived therefrom are renowned for their bioactivity. Thus, it is evaluated how introducing sulfate moieties can influence the interaction of agarose hydrogels with cells. (ii) Tosylated agarose derivatives (TOSA) with DStosyl ≤ 1.8 were prepared as activated intermediates. The derivatives showed a unique transition from regioselective G-6 to non-preferential G-6/LA-2 substitution depending on whether the reaction was performed in the absence or presence of LiCl. By quantitative nucleophilic displacement reaction, azido-deoxy-agarose derivatives were obtained that showed thermoreversible gelation at DSazide &lt; 0.5. The functional hydrogels obtained are highly versatile and it is studied how they can be further functionalized directly in the gel state (e.g., with dyes, drugs, affinity ligands) by exploiting “azide-alkyne click chemistry”. The current approach is well suited to prepare novel highly porous PS materials. It is demonstrated how specific functionalities can be introduced into agarose based hydrogels and how the chemical derivatization affects the gel formation and properties. Based on the presented results, highly functional hydrogels for specific bio-applications can be tailored. Moreover, further conversion into organo-, xero-, and aerogels is feasible.

Functional polysaccharide hydrogels through chemical derivatization of agarose

253rd National Meeting (2017)

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