Senescent cells in tissue engineering

Tissue engineers have long worked to develop cells, biomaterial matrices, and signaling molecules designed to restore or promote the repair of lost or damaged tissue. Senescent cells (SnCs), that is, cells that have entered permanent cell-cycle arrest, exert powerful cell non-autonomous effects on their local environments. As such, SnCs influence cell fates and pathologies in adult tissue, including in settings where tissue engineers have directed their efforts. Here, we compare transient SnCs in tissue repair, contrasted with chronic SnCs in osteoarthritic pathology and the foreign-body response. Then, we discuss recent advances in strategies to control the presence and downstream effects of SnCs in tissues, such as immunomodulatory biomaterials, human trials of senolytic molecules, and senescent-cell-directed CAR-T therapy.