Hiemstra, C. Novel in situ forming, degradable dextran hydrogels by michael addition chemistry synthesis, rheology, and degradation

Hiemstra, C., Aa, L.J. van der, Zhong, Z., Dijkstra, P.J. & Feijen, J

Macromolecules, 40, 1165-1173

Various vinyl sulfone functionalized dextrans with degrees of substitution ranging from 2 to 22 were conveniently prepared by a one-pot synthesis procedure at room temperature. This procedure involved reaction of a mercaptoalkanoic acid with an excess amount of divinyl sulfone yielding vinyl sulfone alkanoic acid, followed by conjugation to dextran using N,N‘-dicyclohexylcarbodiimide (DCC)/4-(dimethylamino)pyridinium 4-toluenesulfonate as a catalyst system. By using two different mercaptoalkanoic acids, 3-mercaptopropionic acid (1a) and 4-mercaptobutyric acid (1b), dex-VS conjugates with either an ethyl spacer or a propyl spacer between the thioether and ester groups were obtained. Linear and four-arm mercaptopoly with two or four thiol groups were also prepared. Hydrogels were rapidly formed in situ under physiological conditions by Michael type addition upon mixing aqueous solutions of dex-VS and multifunctional PEG-SH at a concentration of 10−20% w/v. The gelation time ranged from 0.5 to 7.5 min, depending on the DS, concentration, dextran molecular weight, and PEG-SH functionality. Rheological studies showed that these dextran hydrogels are highly elastic. The storage modulus increased with increasing DS, concentration, and dextran molecular weight, and hydrogels with a broad range of storage moduli from 3 to 46 kPa were obtained. Swelling/degradation studies revealed that these dextran hydrogels have a low initial swelling and are degradable under physiological conditions. The degradation time varied from 3 to 21 days depending on the DS, concentration, dextran molecular weight, and PEG-SH functionality. Interestingly, dex-Pr-VS hydrogels showed prolonged degradation times, but otherwise similar properties compared to dex-Et-VS hydrogels.