An improved injectable polysaccharide hydrogel: modified gellan gum for long-term cartilage regeneration in vitro

摘要

Polysaccharide-based hydrogels have been proven promising in tissue engineering applications due to their good biocompatibility, controllable properties and abundance, and are therefore in great demand as therapeutic cell vehicles. Gellan gum, a natural polysaccharide and FDA-approved food additive, has been well exploited in food and pharmaceutical industries. For tissue engineering purposes, however, gellan-based hydrogels need to be modified in order to meet the requirement of encapsulating living cells while maintaining their injectability, because the gelling point of this temperature-dependent gel is too high (above 42 °C). This study started from chemically scissoring {via oxidative cleavage) the gellan backbones to optimize the gelation temperature for injection as a result of down-regulating their molecular size. Chondrocytes were then seeded into the modified gellan gels, the cytocompatibility and the capability to promote in vitro tissue regeneration of which were evaluated. Notably, chondrocytic constructs based on modified gellan gel were kinetically monitored for 150 days in comparison with those based on agarose gel, showing superiority for long-term cartilaginous development in terms of many aspects such as cell proliferation and specific matrix formation. Biochemical analysis, histological staining, and immunofluorescent observation indicate that the modified gellan is able to retain the chondrocytes viability, enhance the extracellular matrix (ECM) secretion and maintain normal phenotype, which demonstrates that gellan is a potential and promising injectable vehicle for therapeutic chondrocyte delivery.