C-1: The use of engineering modeling in designing cryopreservation protocols for articular cartilage

The transplantation of bone-bearing living articular cartilage is an effective treatment for joint injury and disease. Widespread access to this treatment, however, will require the ability to cryopreserve and bank this tissue. The cryopreservation of articular cartilage has been studied for more than 50years, with early unsuccessful attempts at freezing of cartilage slices [R.C. Curran, T. Gibson, Proc. R. Soc. Lond. B 144 (1956) 572] and the first successful cryopreservation of isolated chondrocytes reported in 1965 [A.U. Smith, Nature 205 (1965) 782]. Recently, our group developed a protocol to cryopreserve human full-thickness articular cartilage attached to bone resulting in chondrocyte membrane integrity of 75.4±12.1% with functionality of chondrocytes confirmed by a metabolic assay and the ability of extracted, pellet-cultured chondrocytes to produce of collagen II and sulfated glycosaminoglycans at levels similar to healthy controls [N.M. Jomha et al., Biomaterials 33 (2012) 6061]. This protocol, aimed at vitrifying the tissue, requires the addition of four different mixtures of four different cryoprotectants added at different temperatures for specific periods of time. To develop this protocol, we relied heavily on engineering modeling. This presentation will review our research over the past 10years on modeling of various key phenomena relevant to the cryopreservation of articular cartilage including solution thermodynamics; water transport; and the transport, toxicity, and vitrifiability of cryoprotectants. The research being reviewed was funded primarily by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, Alberta Innovates, and the Edmonton Orthopaedic Research Committee. J.A.W. Elliott holds a Canada Research Chair in Thermodynamics.