Abstract Maintaining the integrity of articular cartilage is paramount to joint health and function. Under constant mechanical stress, articular cartilage is prone to injury that often extends to the underlying subchondral bone. In this study, we incorporated arginine–aspartate–glycine (RGD) peptide into chondroitin sulfate-based cryogel for hyaline cartilage regeneration. Known to promote cell adhesion and proliferation, RGD peptide is a double-edged sword for cartilage regeneration. Depending on the peptide availability in the microenvironment, RGD may aid in redifferentiation of dedifferentiated chondrocytes by mimicking physiological cell-matrix interaction or inhibit chondrogenic phenotype via excessive cell spreading. Here, we observed an increase in chondrogenic phenotype with RGD concentration. The group containing the highest RGD concentration (3 mM; RGD group) experienced a 24-fold increase in COL2 expression in the 1st week of in vitro culture and formed native cartilage-resembling ectopic tissue in vivo. No sign of dedifferentiation (COL1) was observed in all groups. Within the concentration range tested (0–3 mM RGD), RGD promotes chondrocyte redifferentiation after monolayer expansion and thus, formation of hyaline cartilage tissue.
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