Biological hydrogel synthesized from hyaluronic acid, gelatin and chondroitin sulfate by click chemistry

Abstract

In order to mimic the natural cartilage extracellular matrix, which is composed of core proteins and glycosaminoglycans, a biological hydrogel was synthesized from the biopolymers hyaluronic acid (HA), chondroitin sulfate (CS) and gelatin via click chemistry. HA and CS were modified with 11-azido-3,6,9-trioxaundecan-1-amine (AA) and gelatin was modified with propiolic acid (PA). The molecular structures were verified by 1H nuclear magnetic resonance, infrared spectroscopy and elemental analysis, giving substitution degrees of 29%, 89% and 44% for HA–AA, CS–AA and gelatin–PA (G–PA), respectively. The –N3 groups of HA–AA and CS–AA were reacted with the acetylene groups of G–PA, catalyzed by Cu(I), to form triazole rings, thereby forming a cross-linked hydrogel. The gelation time was decreased monotonically with increasing Cu(I) concentration up to 0.95mgml−1. The hydrogel obtained was in a highly swollen state and showed the characteristics of an elastomer. Incubation in phosphate-buffered saline for 4weeks resulted in a weight loss of up to 45%. Moreover, about 20% gelatin and 10% CS were released from the hydrogel in 2weeks. In vitro cell culture showed that the hydrogel could support the adhesion and proliferation of chondrocytes.