Exploring the role of directly coupled alternating electric fields on chondrocyte morphology and redifferentiation capacity with a focus on sex differences.

Purpose: In cell-based therapies addressing articular cartilage lesions, a central challenge is to avoid the formation of fibrous cartilage resulting from dedifferentiation processes. Electrical stimulation emerges as a promising approach for promoting chondrocytic redifferentiation. This study investigated the effects of varying electric fields on morphological changes and the redifferentiation capacity of human chondrocytes with regard to alterations in sex. Methods: Chondrocytes, isolated from the articular cartilage of male and female patients undergoing total knee replacement, were exposed to alternating electric fields of varying strengths ranging from 0.8 to 1.2, 15 to 20 and 100 to 140 V/m. Afterwards, cell morphology and viability, as well as the deposition of collagen (Col) 1 and 2, were evaluated. Results: Following electrical stimulation, in particular at 15-20 V/m, an increase in the Col2/Col1 ratio and an elevated proportion of rounded, chondrocyte-like cell morphology were observed, indicating a promoting effect on the redifferentiation of chondrocytes. Comparative analysis between both sexes revealed that chondrocytes from female donors exhibit higher Col1 synthesis rates, a decreased Col2/Col1 ratio, and a higher proportion of elongated, fibroblast-like cells compared to chondrocytes derived from male donors. Conclusion: Our in vitro study suggests that chondrocytes from male donors are more prone to re-differentiate after electrical stimulation. Level of Evidence: N/A.