Modeling the addition/removal of dimethyl sulfoxide into/from articular cartilage treated with the liquidus-tracking method

Abstract

The successful preservation of articular cartilage (AC) is of great clinical and scientific significance. The vitreous cryopreservation of AC through the liquidus-tracking (LT) method has achieved satisfactory levels of post-warming chondrocyte survival, but the design of the entire procedure could be improved further. Mathematical modeling would help to better understand the nature and features of the LT process as experienced by the AC sample, possibly providing additional instructive data useful for guiding experimental design. In this paper, the addition/removal of the cryoprotectant dimethyl sulfoxide (Me2SO) into/from the LT-treated AC was modeled and studied numerically. The cryoprotectant permeation model and the cell membrane transport model were combined, and the spatiotemporal concentrations of Me2SO in the AC matrix and the chondrocytes were profiled. In addition, the possible injuries to the cell were predicted based on the biophysical properties of chondrocytes under both the stepwise and the continuous LT protocols. Based on these results, improvements to the stepwise LT method were proposed. Compared to the existing protocol, these improvements might eliminate two processing steps and reduce the protocol duration by 35%. Decreasing the number of processing steps and protocol duration not only saves labor and material resources, but also lowers the risk that chondrocytes will incur toxicity- and chilling-associated injury.