Nanowarming and ice-free cryopreservation of large sized, intact porcine articular cartilage
Published in Nanowarming, Vitrification.
Peng Chen, Shangping Wang, Zhenzhen Chen, Pengling Ren, R. Glenn Hepfer, Elizabeth D. Greene, Lia H. Campbell, Kristi L. Helke, Xingju Nie, Jens H. Jensen, Cherice Hill, Yongren Wu, Kelvin G. M. Brockbank & Hai Yao
Abstract
Successful organ or tissue long-term preservation would revolutionize biomedicine. Cartilage cryopreservation enables prolonged shelf life of articular cartilage, posing the prospect to broaden the implementation of promising osteochondral allograft (OCA) transplantation for cartilage repair. However, cryopreserved large sized cartilage cannot be successfully warmed with the conventional convection warming approach due to its limited warming rate, blocking its clinical potential. Here, we develope a nanowarming and ice-free cryopreservation method for large sized, intact articular cartilage preservation. Our method achieves a heating rate of 76.8 °C min-1, over one order of magnitude higher than convection warming (4.8 °C min-1). Using systematic cell and tissue level tests, we demonstrate the superior performance of our method in preserving large cartilage. A depth-dependent preservation manner is also observed and recapitulated through magnetic resonance imaging and computational modeling. Finally, we show that the delivery of nanoparticles to the OCA bone side could be a feasible direction for further optimization of our method. This study pioneers the application of nanowarming and ice-free cryopreservation for large articular cartilage and provides valuable insights for future technique development, paving the way for clinical applications of cryopreserved cartilage.
Introduction
Organ or bulk tissue transplantation has saved millions of lives and improved the quality of life for patients suffering from organ failure or tissue diseases1,2. However, the number of organs and tissues ready for transplantation is far from reaching the patient population’s needs. For instance, in 2020, 39,036 organ transplantations were performed in the United States while 55,121 new candidates were added to the waitlist3; many patients die while waiting for organ transplantation. Despite the huge unmet demand for organs and tissues, the disappointing fact is that many organs and tissues are not viable for implantation and are discarded because they reach the maximum postmortem preservation time limit1,4. In the case of organ transplantation, up to 70% of donor organs expire before reaching patients1,4. Achieving long-term organ and tissue preservation is critical to improving utilization rates and alleviating existing shortages.