Bioinspired chondroitin sulfate/poly(levodopa) hydrogels as photothermal platforms for NIR controlled drug release and cartilage tissue engineering.

Stimuli-responsive hydrogels capable of combining tissue regeneration with on-demand drug delivery represent an attractive strategy for cartilage repair. In this work, bioinspired chondroitin sulfate/poly(levodopa) (CS/P(L-DOPA)) hydrogels were prepared through EDC/NHS-mediated self-crosslinking of CS followed by the in situ polymerization of L-DOPA to generate a secondary eumelanin photothermal network. The hydrogels were characterized by FTIR spectroscopy, swelling measurements, SEM, photothermal performance, NIR-triggered ibuprofen release, cytocompatibility, and chondrogenic differentiation assays. The incorporation of P(L-DOPA) preserved the interconnected porous morphology while reducing equilibrium swelling under physiological conditions through additional intermolecular interactions. CS/P(L-DOPA) hydrogels exhibited an efficient photothermal conversion upon NIR irradiation, reaching temperatures of 43-46 °C. NIR irradiation promotes the ibuprofen release from the hydrogels, demonstrating remote-controlled drug delivery. In vitro studies confirmed cell viabilities above 80% in L-929 fibroblasts and dental pulp stem cells, while cytoskeletal staining revealed enhanced cell organization. Safranin O and Alcian Blue staining showed an increase in glycosaminoglycan- and proteoglycan-rich extracellular matrix deposition, consistent with a chondrogenic response of the stem cells. These findings demonstrate the potential of CS/P(L-DOPA) hydrogels as a multifunctional platform for NIR-controlled drug delivery and cartilage tissue engineering.