Engineered hydrogels for boosting chimeric antigen receptor (CAR)-cell therapy: strategies and biomedical applications.

Chimeric antigen receptor (CAR)-cell therapy has emerged as a revolutionary approach to treat various diseases, including cancers and non-cancer diseases. However, as a type of living drug, the therapeutic performance and persistence of CAR cells can be markedly affected by multiple factors, from in vitro manufacturing to in vivo conditions. In recent years, bioactive materials, especially hydrogel-based strategies, have emerged as powerful tools to improve ex vivo and in vivo CAR-cell therapy. In brief, engineered hydrogels might regulate CAR-cell expansion or activation states during manufacturing and as models for cell functional assessments in vitro; in vivo, hydrogels might preserve CAR cells and regulate their retention, release and tissue infiltration while reprogramming adverse disease microenvironments. Despite promising advances, the progress, limitations and future directions of this field have not been comprehensively evaluated. In this mini-review, we evaluate the framework of hydrogel-based strategies in boosting CAR-cell therapy over the past five years, from cell manufacturing to functional improvement. Together, current findings suggest that engineered hydrogels provide spatial and temporal cues to enhance CAR-cell manufacturing and therapeutic capacity. This review might provide insights into design principles for developing tailored hydrogels to improve CAR-cell therapies to treat diverse types of diseases.