Light-driven biofabrication of 3D stem-cell chondrogenic tissue analogues

Articular cartilage (AC) defects are one of the major causes of immobility and poor quality of life for millions of individuals worldwide. Current medical therapies have proven to be insufficient for the long-term regeneration of AC defects. Alternatively, the application of bioprinting in tissue engineering (TE) allows for the fabrication of complex 3D constructs via the precise spatial deposition of multiple cells and biomaterials. When integrated with human pluripotent stem cells (hPSCs), bioprinting opens up the possibility to generate human chondroprogenitor-containing tissue substitutes that can then be transplanted into AC defects and produce cartilage to repair the defect. cartilage. Despite significant progress, the current differentiation protocols for hPSCs towards chondrocytes still present several challenges, including the high cost, inducing factor batch to batch variation and precise timing of administered growth factors and cellular receptor expression together with poor precision of pathway activation. Based on previous work [1], we hypothesise that through using optogenetics, which combines optical and genetic approaches to control cell signalling and hence phenotype, cell-signalling receptors that are critical for regulation of chondrogenesis can be replaced with engineered light sensitive receptors, allowing activation of signalling by specific light wavelengths. This will enable precision fine-tuning of differentiation in 3D bioprinted cell-laden hydrogels by light. If successful, this innovative approach would enable, for the first time, the dynamic manipulation of cell signalling pathways with high spatio-temporal precision.