Tissue engineered cartilage constructs have potential clinical applications in human healthcare. Their effective utilization is, however, hampered by the lack of an optimal cryopreservation procedure that ensures their availability as and when required at the patient’s bedside. Cryopreservation-induced stress represents a major barrier towards the cryopreservation of such tissue constructs, and they remain a scientific challenge despite the significant progress in the long-term storage and banking of isolated chondrocytes and thin cartilage tissue slices. These stresses are caused by intra- and extracellular ice crystallization, cryoprotectant (CPA) toxicity, suboptimal rates of cooling and warming, osmotic imbalance, and altered intracellular pH that might cause cellular death and/or a disruption of extracellular matrix (ECM). This paper reviews the cryopreservation-induced stresses on tissue engineered cartilages and discusses how they influence the integrity of the tissue during its long-term preservation. We have also reported how various antioxidants, vitamins, and plant extracts have been used to inhibit and overcome the stress during cryopreservation and provide promising results. Based on the reviewed information, the paper has also proposed some novel ways which might help in increasing the postthawing cell viability of cryopreserved cartilage. 1. Introduction Defects and diseases of articular cartilage are common ailments in humans. Osteoarthritis, the most common form of arthritis involving the inflammation of the articular cartilage, is observed in 60–70% of the people above the age of 65 [1]. In the USA alone, over 27 million people are known to be suffering from these articular defects [2]. Cartilage also has a limited regeneration capacity, and hence, available therapeutic modalities provide a temporary relief and have a limited clinical success. In recent years, with the rapid advancement in the tissue engineering, artificial cartilages engineered from biopolymers and stem cells have shown promising clinical results, and therefore, they have been envisaged as a future therapy for an effective and long-term clinical outcome. Preservation of tissue engineered articular cartilage is also essential for their widespread commercialisation so that they can be provided to patients as and when required. The growing need and limited availability of viable transplantable cartilaginous tissues have necessitated the development and optimization of the preservation techniques and banking of tissue engineered cartilage constructs. Preservation of
References
[1]
K. Baker, J. Goggins, H. Xie, et al., “A randomized crossover trial of a wedged insole for treatment of knee osteoarthritis,” Arthritis and Rheumatism, vol. 56, no. 4, pp. 1198–1203, 2007.
[2]
B. D. Furman, S. A. Olson, and F. Guilak, “The development of posttraumatic arthritis after articular fracture,” Journal of Orthopaedic Trauma, vol. 20, no. 10, pp. 719–747, 2006.
[3]
R. Sharma, G. K. Law, K. Rekieh et al., “A novel method to measure cryoprotectant permeation into intact articular cartilage,” Cryobiology, vol. 54, no. 2, pp. 196–203, 2007.
[4]
J. Y. Bae, K. Matsumura, S. Wakitani, A. Kawaguchi, S. Tsutsumi, and S.-H. Hyon, “Beneficial storage effects of epigallocatechin-3-o-gallate on the articular cartilage of rabbit osteochondral allografts,” Cell Transplantation, vol. 18, no. 5, pp. 505–512, 2009.
[5]
S. K. Williams, D. Amiel, S. T. Ball et al., “Prolonged storage effects on the articular cartilage of fresh human osteochondral allografts,” Journal of Bone and Joint Surgery A, vol. 85, no. 11, pp. 2111–2120, 2003.
[6]
J. Bakhach, “The cryopreservation of composite tissues: principles and recent advancement on cryopreservation of different type of tissues,” Organogenesis, vol. 5, no. 3, pp. 119–126, 2009.
[7]
W. F. Enneking and E. R. Mindell, “Observations on massive retrieved human allografts,” Journal of Bone and Joint Surgery A, vol. 73, no. 8, pp. 1123–1142, 1991.
[8]
M. Salai, U. Givon, Y. Messer, and R. von Versen, “Electron microscopic study on the effects of different preservation methods for meniscal cartilage,” Annals of Transplantation, vol. 2, no. 1, pp. 52–54, 1997.
[9]
G. Cetinkaya and S. Arat, “Cryopreservation of cartilage cell and tissue for biobanking,” Cryobiology, vol. 63, no. 3, pp. 292–297, 2011.
[10]
J. D. Boer, C. V. Blitterswijk, P. Thomsen et al., “Chapter 13: cryobiology,” in Tissue Engineering, Academic Press, 2008.
[11]
S. C. Chan, S. K. Lam, V. Y. Leung, D. Chan, K. D. Luk, and K. M. Cheung, “Minimizing cryopreservation-induced loss of disc cell activity for storage of whole intervertebral discs,” European Cells & Materials, vol. 19, pp. 273–283, 2010.
[12]
K. D. Luk, D. K. Ruan, D. S. Lu, and Z. Q. Fei, “Fresh frozen intervertebral disc allografting in a bipedal animal model,” Spine, vol. 28, no. 9, pp. 864–869, 2003.
[13]
J. Bujia, D. Kremer, H. Sudhoff, E. Viviente, C. Sprekelsen, and E. Wilmes, “Determination of viability of cryopreseved cartilage grafts,” European Archives of Otorhinolaryngol, vol. 252, no. 1, pp. 30–34, 1995.
[14]
C. A. Acosta, I. Izal, P. Ripalda, and F. Forriol, “Cell viability and protein composition in cryopreserved cartilage,” Clinical Orthopaedics and Related Research, no. 460, pp. 234–239, 2007.
[15]
D. E. Pegg, M. C. Wusteman, and L. Wang, “Cryopreservation of articular cartilage—part 1: conventional cryopreservation methods,” Cryobiology, vol. 52, no. 3, pp. 335–346, 2006.
[16]
Y. C. Song, F. G. Lightfoot, Z. Chen, M. J. Taylor, and K. G. M. Brockbank, “Vitreous preservation of rabbit articular cartilage,” Cell Preservation Technology, vol. 2, no. 1, pp. 67–74, 2004.
[17]
Y. C. Song, H. A. Yuehuei, K. K. Qian, et al., “Ice-free cryopreservation of articular cartilage,” Tissue Engineering, vol. 8, no. 6, p. 1181, 2002.
[18]
B. Weber, M. Y. Emmert, R. Schoenauer, C. Brokopp, L. Baumgartner, and S. P. Hoerstrup, “Tissue engineering on matrix: future of autologous tissue replacement,” Seminars in Immunopathology, vol. 33, no. 3, pp. 307–315, 2011.
[19]
J. Leor, Y. Amsalem, and S. Cohen, “Cells, scaffolds, and molecules for myocardial tissue engineering,” Pharmacology and Therapeutics, vol. 105, no. 2, pp. 151–163, 2005.
[20]
V. Vindigni, R. Cortivo, L. Iacobellis, G. Abatangelo, and B. Zavan, “Hyaluronan benzyl ester as a scaffold for tissue engineering,” International Journal of Molecular Sciences, vol. 10, no. 7, pp. 2972–2985, 2009.
[21]
A. G. Mikos, S. W. Herring, P. Ochareon et al., “Engineering complex tissues,” Tissue Engineering, vol. 12, no. 12, pp. 3307–3339, 2006.
[22]
K. A. Athanasiou, E. M. D. Davis, and C. H. Jerry, Articular Cartilage Tissue Engineering, Synthesis Lectures on Tissue Engineering, 2009.
[23]
D. S. Vara, H. J. Salacinski, R. Y. Kannan, L. Bordenave, G. Hamilton, and A. M. Seifalian, “Cardiovascular tissue engineering: state of the art,” Pathologie Biologie, vol. 53, no. 10, pp. 599–612, 2005.
[24]
M. Risbud, “Tissue engineering: implications in the treatment of organ and tissue defects,” Biogerontology, vol. 2, no. 2, pp. 117–125, 2001.
[25]
J. van der Valk, D. Mellor, R. Brands et al., “The humane collection of fetal bovine serum and possibilities for serum-free cell and tissue culture,” Toxicology in Vitro, vol. 18, no. 1, pp. 1–12, 2004.
[26]
C.-Y. Liu, Y.-H. Liu, S.-M. Lin et al., “Apoptotic neutrophils undergoing secondary necrosis induce human lung epithelial cell detachment,” Journal of Biomedical Science, vol. 10, no. 6, pp. 746–756, 2003.
[27]
H. Jaeschke and J. J. Lemasters, “Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury,” Gastroenterology, vol. 125, no. 4, pp. 1246–1257, 2003.
[28]
W. Wilson, C. C. Van Donkelaar, B. Van Rietbergen, and R. Huiskes, “A fibril-reinforced poroviscoelastic swelling model for articular cartilage,” Journal of Biomechanics, vol. 38, no. 6, pp. 1195–1204, 2005.
[29]
A. Maroudas and P. Bullough, “Permeability of articular cartilage,” Nature, vol. 219, no. 5160, pp. 1260–1261, 1968.
[30]
F. Guilak, G. R. Erickson, and H. P. Ting-Beall, “The effects of osmotic stress on the viscoelastic and physical properties of articular chondrocytes,” Biophysical Journal, vol. 82, no. 2, pp. 720–727, 2002.
[31]
F. Guilak, B. C. Meyer, A. Ratcliffe, and V. C. Mow, “The effects of matrix compression on proteoglycan metabolism in articular cartilage explants,” Osteoarthritis and Cartilage, vol. 2, no. 2, pp. 91–101, 1994.
[32]
A. Maroudas, “Physiochemical properties of articular cartilage,” in Adult Articular Cartilage, M. A. R. Freeman, Ed., pp. 215–290, Pitman Medical, Tunbridge Wells, UK, 1979.
[33]
F. Guilak, “Compression-induced changes in the shape and volume of the chondrocyte nucleus,” Journal of Biomechanics, vol. 28, no. 12, pp. 1529–1541, 1995.
[34]
M. Wong, P. Wuethrich, M. D. Buschmann, P. Eggli, and E. Hunziker, “Chondrocyte biosynthesis correlates with local tissue strain in statically compressed adult articular cartilage,” Journal of Orthopaedic Research, vol. 15, no. 2, pp. 189–196, 1997.
[35]
J. Schiller, M. Wagner, A. Werner, K. Arnold, and W. Grunder, “The effect of temperature on the storage of porcine articular cartilage—an NMR-Study,” Biomedizinische Technik/Biomedical Engineering, vol. 40, no. 1-2, pp. 19–23, 1995.
[36]
N. Mukherjee, Z. Chen, A. Sambanis, and Y. Song, “Effects of cryopreservation on cell viability and insulin secretion in a model Tissue-Engineered Pancreatic Substitute (TEPS),” Cell Transplantation, vol. 14, no. 7, pp. 449–456, 2005.
[37]
N. M. Jomha, P. C. Anoop, and L. E. McGann, “Intramatrix events during cryopreservation of porcine articular cartilage using rapid cooling,” Journal of Orthopaedic Research, vol. 22, no. 1, pp. 152–157, 2004.
[38]
S. Zheng, Y. Xia, A. Bidthanapally, F. Badar, I. Ilsar, and N. Duvoisin, “Damages to the extracellular matrix in articular cartilage due to cryopreservation by microscopic magnetic resonance imaging and biochemistry,” Magnetic Resonance Imaging, vol. 27, no. 5, pp. 648–655, 2009.
[39]
K. Muldrew, K. Novak, H. Yang, R. Zernicke, N. S. Schachar, and L. E. McGann, “Cryobiology of articular cartilage: ice morphology and recovery of chondrocytes,” Cryobiology, vol. 40, no. 2, pp. 102–109, 2000.
[40]
T. M. Farooque, Biochemical and Mechanical Stimuli for Improved Material Properties and Preservation of Tissue-Engineered Cartilage, Georgia Institute of Technology, 2008.
[41]
K. Y. Teo, J. C. Dutton, and B. Han, “Spatiotemporal measurement of freezing-induced deformation of engineered tissues,” Journal of Biomechanical Engineering, vol. 132, no. 3, article 031003, 8 pages, 2010.
[42]
R. H. J. Das, G. J. V. M. Van Osch, M. Kreukniet, J. Oostra, H. Weinans, and H. Jahr, “Effects of individual control of pH and hypoxia in chondrocyte culture,” Journal of Orthopaedic Research, vol. 28, no. 4, pp. 537–545, 2010.
[43]
P. I. Milner, R. J. Wilkins, and J. S. Gibson, “Cellular physiology of articular cartilage in health and disease,” in Principles of Osteoarthritis- Its Definition, Character, Derivation and Modality-Related Recognition, pp. 567–590, Intech, 2012.
[44]
M. D. Valeria, J. S. Mort, S. Leverty, et al., “Cleavage of telopeptides causes the depolymerisation of fibrillar collagen network, and cleavage of the triple helix present in collagen results in depolymerisation accompanied by denaturation,” The American Journal of Pathology, vol. 173, p. 1, 2008.
[45]
Y. Zheng, H. Lv, Y. Wang, H. Lu, L. Qing, and T. Xi, “Performance of novel bioactive hybrid hydrogels in vitro and in vivo used for artificial cartilage,” Biomedical Materials, vol. 4, no. 1, Article ID 015015, 2009.
[46]
P. Mazur, “Freezing of living cells: mechanisms and implications,” The American Journal of Physiology, vol. 247, no. 3, pp. C125–C142, 1984.
[47]
B. Han, E. D. Grassl, V. H. Barocas, J. E. Coad, and J. C. Bischof, “A cryoinjury model using engineered tissue equivalents for cryosurgical applications,” Annals of Biomedical Engineering, vol. 33, no. 7, pp. 972–982, 2005.
[48]
A. Mobasheri, “Ion transport in chondrocytes: membrane transporters involved in intracellular ion homeostasis and the regulation of cell volume, free [Ca2+] and pH,” Histology and Histopathology, vol. 13, no. 3, pp. 893–910, 1998.
[49]
C. Z. Jin, J.-H. Cho, B. H. Choi et al., “The maturity of tissue-engineered cartilage in vitro affects the repairability for osteochondral defect,” Tissue Engineering A, vol. 17, no. 23-24, pp. 3057–3065, 2011.
[50]
R. Vasita and D. S. Katti, “Nanofibers and their applications in tissue engineering,” International Journal of Nanomedicine, vol. 1, no. 1, pp. 15–30, 2006.
[51]
M. R. Seddighi, D. J. Griffon, D. J. Schaeffer, B. A. Fadl-Alla, and J. A. C. Eurell, “The effect of chondrocyte cryopreservation on cartilage engineering,” Veterinary Journal, vol. 178, no. 2, pp. 244–250, 2008.
[52]
R. F. Loeser, “Chondrocyte integrin expression and function,” Biorheology, vol. 37, no. 1-2, pp. 109–116, 2000.
[53]
D. L. Reid, M. B. Aydelotte, and J. Mollenhauer, “Cell attachment, collagen binding, and receptor analysis on bovine articular chondrocytes,” Journal of Orthopaedic Research, vol. 18, no. 3, pp. 364–373, 2000.
[54]
C. Ruiz-Romero, V. Calamia, J. Mateos et al., “Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance,” Molecular and Cellular Proteomics, vol. 8, no. 1, pp. 172–189, 2009.
[55]
G. K. Gorti, J. Lo, S. Falsafi et al., “Cartilage tissue engineering using cryogenic chondrocytes,” Archives of Otolaryngology—Head and Neck Surgery, vol. 129, no. 8, pp. 889–893, 2003.
[56]
K. Mansfield, C. C. Teixeira, C. S. Adams, and I. M. Shapiro, “Phosphate ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism,” Bone, vol. 28, no. 1, pp. 1–8, 2001.
[57]
K. A. Almansoori, V. Prasad, J. F. Forbes, et al., “Cryoprotective agent toxicity interactions in human articular chondrocytes,” Cryobiology, vol. 64, no. 3, pp. 185–191, 2012.
[58]
E. A. Kennedy, D. S. Tordonado, and S. M. Duma, “Effects of freezing on the mechanical properties of articular cartilage,” Biomedical Sciences Instrumentation, vol. 43, pp. 342–347, 2007.
[59]
T. L. Willett, R. Whiteside, P. M. Wild, U. P. Wyss, and T. Anastassiades, “Artefacts in the mechanical characterization of porcine articular cartilage due to freezing,” Proceedings of the Institution of Mechanical Engineers H, vol. 219, no. 1, pp. 23–29, 2005.
[60]
K. A. Athanasiou, M. P. Rosenwasser, J. A. Buckwalter, T. I. Malinin, and V. C. Mow, “Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage,” Journal of Orthopaedic Research, vol. 9, no. 3, pp. 330–340, 1991.
[61]
A. J. Kerin, M. R. Wisnom, and M. A. Adams, “The compressive strength of articular cartilage,” Proceedings of the Institution of Mechanical Engineers H, vol. 212, no. 4, pp. 273–280, 1998.
[62]
A. de Wolf, Future Directions in Human Cryopreservation Combinational Pharmacotherapy, 2007.
[63]
K. Muldrew, M. Hurtig, K. Novak, N. Schachar, and L. E. McGann, “Localization of freezing injury in articular cartilage,” Cryobiology, vol. 31, no. 1, pp. 31–38, 1994.
[64]
X. Xu, Z. F. Cui, R. J. Wilkins, and J. P. G. Urban, “Intracellular pH changes in isolated bovine articular chondrocytes during the loading and removal of cryoprotective agents,” Cryobiology, vol. 46, no. 2, pp. 161–173, 2003.
[65]
A. Abazari Torqabeh, Modeling the transport of cryoprotective agents in articular cartilage for cryopreservation [Ph.D. thesis], 2011.
[66]
E. Wernike, Z. Li, M. Alini, and S. Grad, “Effect of reduced oxygen tension and long-term mechanical stimulation on chondrocyte-polymer constructs,” Cell and Tissue Research, vol. 331, no. 2, pp. 473–483, 2008.
[67]
M. Deberg, A. Labasse, S. Christgau, et al., “New serum biochemical markers (Coll 2-1 and Coll 2-1 NO2) for studying oxidative-related type II collagen network degradation in patients with osteoarthritis and rheumatoid arthritis,” Osteoarthritis and Cartilage, vol. 13, no. 3, pp. 258–265, 2005.
[68]
F. Zaman, D. Chrysis, K. Huntjens, B. Fadeel, and L. S?vendahl, “Ablation of the pro-apoptotic protein bax protects mice from glucocorticoid-induced bone growth impairment,” PLoS ONE, vol. 7, no. 3, article e33168, 2012.
[69]
D. Acehan, X. Jiang, D. G. Morgan, J. E. Heuser, X. Wang, and C. W. Akey, “Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation,” Molecular Cell, vol. 9, no. 2, pp. 423–432, 2002.
[70]
C. Polge, A. U. Smith, and A. S. Parkes, “Revival of spermatozoa after vitrification and dehydration at low temperatures,” Nature, vol. 164, no. 4172, p. 666, 1949.
[71]
Y. Orief, A. Schultze-Mosgau, K. Dafopoulos, and S. Al-Hasani, “Vitrification: will it replace the conventional gamete cryopreservation techniques?” Middle East Fertility Society Journal, vol. 10, no. 3, pp. 171–184, 2005.