The Effect of Physical, Biochemical, and Electrical Culture Conditions on Articular Chondrocytes Used for Cartilage Tissue Engineering: A Narrative Review.

Osteoarthritis is a leading cause of disability, most commonly affecting the articular cartilage of the knee in older individuals. Younger people are also at risk of developing post-traumatic osteoarthritis, including athletes and those with a history of joint injury. Focal cartilage defects can be treated through clinical interventions such as autologous chondrocyte implantation, where cells from the patient are isolated, cultured, and subsequently reimplanted into the defect site. Despite recent clinical advances, there is a lack of standardisation in the preparation of chondrocytes for cartilage tissue engineering therapies, with considerable variation in culture conditions reported in the literature. A major challenge in cell-based cartilage repair is the dedifferentiation of chondrocytes during monolayer expansion, which leads to a change in phenotype. Native articular chondrocytes exhibit a rounded morphology and express collagen type II and aggrecan, whilst dedifferentiated cells adopt a fibroblastic phenotype, characterised by an elongated morphology and increased expression of collagen type I. This review summarises the key physical, biochemical, and mechanical factors that mitigate chondrocyte dedifferentiation to support the maintenance of a chondrogenic phenotype and preserve the capacity of cells to redifferentiate. A mechanistically informed approach to chondrocyte culture will enhance cartilage tissue engineering therapies.