Chondroitin sulfate (CS), the main component of cartilage extracellular matrix, has attracted attention as a biomaterial for cartilage tissue engineering. However, current CS hydrogel systems still have limitations for application in successful cartilage tissue engineering owing to their unsuitable degradation kinetics, insufficient mechanical similarity, and lack of integration with the native cartilage tissue. In this study, using mussel adhesive-inspired catechol chemistry, we developed a functional CS hydrogel that exhibits tunable physical and mechanical properties as well as excellent tissue adhesion for efficient integration with native tissues. Various properties of the developed catechol-functionalized CS (CS-CA) hydrogel, including swelling, degradation, mechanical properties, and adhesiveness, could be tailored by varying the conjugation ratio of the catechol group to the CS backbone and the concentration of the CS-CA conjugates. CS-CA hydrogels exhibited significantly increased modulus (∼10 kPa) and superior adhesive properties (∼3 N) over conventional CS hydrogels (∼hundreds Pa and ∼0.05 N). In addition, CS-CA hydrogels incorporating decellularized cartilage tissue dice promoted the chondrogenic differentiation of human adipose-derived mesenchymal stem cells by providing a cartilage-like microenvironment. Finally, the transplantation of autologous cartilage dice using tissue-adhesive CS-CA hydrogels enhanced cartilage integration with host tissue and neo-cartilage formation owing to favorable physical, mechanical, and biological properties for cartilage formation. In conclusion, our study demonstrated the potential utility of the CS-CA hydrogel system in cartilage tissue reconstruction.
Keywords: cartilage tissue engineering; cartilage-like microenvironment; chondrogenic differentiation; chondroitin sulfate; tissue-adhesive hydrogel.