Human articular cartilage repair: Sources and detection of cytotoxicity and genotoxicity in photo-crosslinkable hydrogel bioscaffolds

Three-dimensional biofabrication using photo-crosslinkable hydrogel bioscaffolds has the potential to revolutionize the need for transplants and implants in joints, with articular cartilage being an early target tissue. However, to successfully translate these approaches to clinical practice, several barriers must be overcome. In particular, the photo-crosslinking process may impact on cell viability and DNA integrity, and consequently on chondrogenic differentiation. In this review, we primarily explore the specific sources of cellular cytotoxicity and genotoxicity inherent to the photo-crosslinking reaction, the methods to analyze cell death, cell metabolism, and DNA damage within the bioscaffolds, and the possible strategies to overcome these detrimental effects. Significance statement Several hurdles need to be addressed before the clinical translation of articular cartilage regeneration procedures using photo-crosslinkable hydrogels. Cellular cytotoxicity and genotoxicity need to be identified and carefully detected to provide an indication of the safety of the repair treatment approach in patients.