Ligand Composition and Coating Density Co-Modulate the Chondrocyte Function on Poly(glycerol-dodecanedioate)

Inducing chondrocyte redifferentiation and promoting cartilaginous matrix accumulation are key challenges in the application of biomaterials in articular cartilage repair. Poly(glycerol-dodecanedioate) (PGD) is a viable candidate for scaffold design in cartilage tissue engineering (CTE). However, the surface properties of PGD are not ideal for cell attachment and growth due to its relative hydrophobicity compared with natural extracellular matrix (ECM). In this study, PGD was coated with various masses of collagen type I or hyaluronic acid, individually or in combination, to generate a cell–material interface with biological cues. The effects of ligand composition and density on the PGD surface properties and shape, metabolic activity, cell phenotype, and ECM production of human articular chondrocytes (hACs) were evaluated. Introducing ECM ligands on PGD significantly improved its hydrophilicity and promoted the chondrocyte’s anabolic activity. The morphology and anabolic activity of hACs on PGD were co-modulated by ligand composition and density, suggesting a combinatorial effect of both coating parameters on chondrocyte function during monolayer culture. Hyaluronic acid and its combination with collagen maintained a round cell shape and redifferentiated phenotype. This study demonstrated the complex mechanism of ligand-guided interactions between cell and biomaterial substrate and the potential of PGD as a scaffold material in the field of CTE.