Photo-driven dynamic hydrogel modulates bone marrow mesenchymal stem cells behavior for enhanced cartilage regeneration

Regenerating damaged cartilage remains a challenge due to limited cell availability and inefficient chondrogenic differentiation. Here, we present a photo-driven dynamic hydrogel with a double-network structure to meet this challenge. The fabrication strategy involves a combination of a photosensitive host-guest network with a covalent network, providing tunable mechanical cues that effectively regulate bone marrow mesenchymal stem cells (BMSCs) behavior within their microenvironment while maintaining macroscopical stability. Employing a two-step stiffness-tunable process mediated by controlled low-dose light exposure, the hydrogel exerts precise control over BMSCs proliferation and orchestrates chondrogenic differentiation, leading to the upregulation of crucial chondrogenic genes, notably SOX9 and ACAN. Empirical evidence derived from histological analysis substantiates the functional efficacy of the hydrogel, confirming the regenerative potential of cartilage tissues. This study presents an innovative and promising strategy for stem cell culture, in vitro differentiation, and cell delivery, with implications for cartilage defect repair and tissue regeneration.