Hydrogels Based On Functionalized Polysaccharides

A process for preparing a functionalized alginate based hydrogel, the process comprising

• i) converting one or more carboxylic acid functional groups of alginate or one or more carboxylate functional groups of alginate salt into TBA carboxylates,
• ii) modifying one or more hydroxyl groups of said alginate, or salt thereof, by reacting one or more hydroxyl groups in the presence of carbodiimidazole followed by precipitation,
• iii) preparing thiol-functionalized PEG derivatives by
• iii1) reacting the intermediates α-amino-ωazido poly (ethylene glycol) with protected 3-mercaptopropanoic acid, followed by simultaneous reduction of the azido group and deprotection of the thiol functionality, to produce PEG I, or
• iii2) conjugating intermediates α-amino-ωazido poly (ethylene glycol) to activated lipoic acid followed by reduction in the presence of LiAlH4 so as to deliver PEG II as mixtures of opened (reduced) and closed (oxidized) forms of the lipoyl functionality, or
• iii3) contacting intermediates α-amino-ωazido poly (ethylene glycol) 1a and 1b with a triazole moiety using a click reaction catalyzed by copper species to produce PEG III,
• iv) grafting the modified alginate with PEG I, PEG II and/or PEG III to allow the formation of a covalent bond between the functionalized alginate and PEG I, PEG II and/or PEG III on one hydroxyl group of said alginate or salt thereof,
• v) purifying alginate grafted to PEG through dialysis and freeze drying.

A heterobifunctional PEG, or a derivative thereof, of formula I, II and/or III:

• wherein
• n=8 to 50;
• R1 is independently selected from NH2, N3, OH, and C1-6 alkyl-CO2H;
• R2 is independently selected from (CH2)pSH, with p=2 to 10,
• with q=2 to 5,
• with m=2 to 10;
• R3 is independently selected from