Effects of the bonding intensity between hyaluronan and gelatin on chondrogenic phenotypic maintenance

Abstract

Although there have been many reports on the use of crosslinked hyaluronic acid and gelatin derivatives as injectable hydrogels in cartilage tissue engineering, however, almost no reports have analyzed the kinds of bonding intensity that were most conducive for the maintenance of cartilage phenotypes. Herein, the biomimetic composite hydrogels based on thiolated hyaluronic acid and modified gelatin derivatives with physical mixed, weak, and strong bonding intensity were fabricated, wherein the thiolated hyaluronic acid ensured the basic network structure of composite hydrogels, and gelatin derivatives endowed the bioactivity to hydrogels. These physicochemical properties of composite hydrogels implied that strong bonding intensity (HA–GSH) contributed to the maintenance of a more uniform pore structure, and increased the ability of water retention and resistance to degradation. Further immunohistochemical and RT-PCR analyses demonstrated that the HA–GSH hydrogel greatly improved the expression level of the associated cartilage matrix and the possibility of hyaline cartilage formation in comparison to the physically blended HA–Gel gel and weak bonding crosslinked HA–GMA gel. Overall, all results proved that strong bonding intensity of the disulfide bonds in the HA–GSH hydrogel was more beneficial for the proliferation of chondrocytes and the maintenance of the hyaline cartilage phenotype, which might provide valuable inspiration for designing cartilage repair scaffolds.