Synthesis of a disulfide cross-linked polygalacturonic acid hydrogel for biomedical applications

Polygalacturonic acid (PGA) hydrogel cross-linked via disulfide bonds was synthesized using a thiol oxidation reaction. PGA was grafted with cysteine to yield thiolated PGA (denoted PGAcys). Per gram, PGA-conjugated cysteine was 725 ± 77 μmol, and the degree of modification was 16.24 %. A PGAcys hydrogel film was fabricated under physiological conditions, with gel content 91.6 % and water content 43.3 %. The PGAcys hydrogel was used as a drug carrier for rosmarinic acid (RA) (denoted PGAcys/RA) and to prevent postsurgical adhesion. The in vitro dynamic release behavior of RA from the PGAcys hydrogel was analyzed. The profiles showed that 80 % of the total RA was released from the hydrogel within 15 min, followed by zero-order kinetic release. Animal implant studies showed that PGAcys and PGAcys/RA hydrogel films reduced adhesion incidence by over 90 %, significantly higher than did Hyaluronate/Carboxymethylcellulose (analogous Seprafilm™) (42 %). The PGAcys/RA hydrogel film also reduced the early inflammatory reaction.