Potential use of alginate beads as a chondrocyte delivery vehicle and stepwise dissolving porogen in a hydrogel scaffold for cartilage tissue engineering

The submicron- or nano-sized pores and uncontrollable degradation of conventional hydrogels have severely constrained cell growth and neo-tissue formation. In this study, alginate beads are explored as both delivery vehicles of chondrocytes and stimuli-responsive porogens within hydrogel scaffolds for cartilage tissue engineering. A typical chondroitin sulfate (CS)-alginate beads composite gel (CS-ABG) is fabricated by photo-encapsulating alginate beads into the CS gel, and subsequently batch-wise dissolution and leaching out of the alginate beads is achieved by twice exposing CS-ABG to chelating agents. The combining and gradual removal of alginate beads effectively modulate the gel's physical properties (e.g. swelling ratio, crosslink density) as well as create macro-scale cavities within CS-ABG. The efficacy of CS-ABG as a scaffold for cartilage tissue engineering is compared with a conventional photocrosslinked CS gel (CS-G). The CS-ABG constructs are developed by co-encapsulating chondrocytes and cell-laden alginate beads within the CS gel body and undergo EDTA treatment on day 7 and 14 of culture, respectively, for stepwise removal of the alginate beads. The chondrocytes cultured in CS-ABG constructs exhibit higher cell viability and proliferation, enhanced cartilage-specific gene expressions as well as ECM production compared with those in CS-G constructs. This study demonstrates the potential of alginate beads as cell delivery vehicles and gradually dissolving porogens within gel scaffolds for cartilage tissue engineering.