Abstract
Oxygenated machine perfusion of human organs has been shown to improve both preservation quality and time duration when compared to the current gold standard: static cold storage. However, existing machine perfusion devices designed for preservation and transportation of transplantable organs are too complicated and organ-specific to merit use as a solution for all organs. This work presents a novel, portable, and nonelectronic device potentially capable of delivering oxygenated machine perfusion to a variety of organs. An innovative pneumatic circuit system regulates a compressed oxygen source that cyclically inflates and deflates silicone tubes, which function as both the oxygenator and perfusion pump. Different combinations of silicone tubes in single or parallel configurations, with lengths ranging from 1.5 to 15.2 m, were evaluated at varying oxygen pressures from 27.6 to 110.3 kPa. The silicone tubes in parallel configurations produced higher peak perfusion pressures (70% increase), mean flow rates (102% increase), and oxygenation rates (268% increase) than the single silicone tubes that had equivalent total lengths. While pumping against a vascular resistance element that mimicked a kidney, the device achieved perfusion pressures (8.4–131.6 mmHg), flow rates (2.0–40.2 mL min−1), and oxygenation rates (up to 388 μmol min−1) that are consistent with values used in previous kidney preservation studies. The nonelectronic device achieved those perfusion parameters using 4.4 L min−1 of oxygen to operate. These results demonstrate that oxygenated machine perfusion can be successfully achieved without any electronic components.
Similar content being viewed by others
Abbreviations
- MP:
-
Machine perfusion
- PBS:
-
Phosphate buffered saline
- PVC:
-
Polyvinyl chloride
- SCS:
-
Static cold storage
- VOPS:
-
Versatile oxygenating perfusion system
- L :
-
Length of tube (m)
- R :
-
Vascular resistance (mmHg min mL−1)
- r :
-
Inner radius of tube (m)
- µ :
-
Greek, small letter Mu, viscosity of PBS (Pa s)
- \(\dot{O}\) 2 :
-
Oxygenation rate (μmol min−1)
- H c :
-
Van ‘t Hoff relationship (mol m−3 Pa−1)
- V sol :
-
Volume of perfusion solution in device (m3)
- ΔP dev :
-
Change in device pressure (Pa)
- t trial :
-
Time of trial (min)
- K :
-
Henry’s law solubility constant for oxygen (mol m−3 Pa−1)
- H :
-
Temperature dependence of the Henry solubility constant (K)
- T amb :
-
Ambient temperature (K)
- T o :
-
Reference temperature (K)
- P amb :
-
Ambient pressure (Pa)
- V i :
-
Initial volume of oxygen in tank (m−3)
- m i :
-
Initial mass of oxygen in tank (kg)
- R :
-
Universal gas constant (J mol−1 K−1)
- \({M}_{{\text{O}}_{2}}\) :
-
Molar mass of oxygen (mol kg−1)
- m f :
-
Final mass of oxygen in tank (kg)
- P f :
-
Final pressure of oxygen tank (Pa)
- P i :
-
Initial pressure of oxygen tank (Pa)
- \({Q}_{{\text{O}}_{2}}\) :
-
Volumetric flow rate of oxygen (L min−1)
- \({\rho }_{{\text{O}}_{2}}\) :
-
Greek, small letter Rho, density of oxygen (kg m−3)
- t total :
-
Time between oxygen tank pressure readings (min)
References
Chandan, G., and M. Cascella. Gas Laws and Clinical Application. 2019.
Chung, K. C., and A. K. Alderman. Replantation of the upper extremity: indications and outcomes. J. Am. Soc. Surg. Hand. 2:78–94, 2002.
D’Alessandro, A. M., J. H. Southard, R. B. Love, and F. O. Belzer. Organ preservation. Surg. Clin. N. Am. 74:1083–1095, 1994.
de Vries, R. J., M. Yarmush, and K. Uygun. Systems engineering the organ preservation process for transplantation. Curr. Opin. Biotechnol. 58:192–201, 2019.
Dillingham, T. R., L. E. Pezzin, and E. J. MacKenzie. Limb amputation and limb deficiency: epidemiology and recent trends in the United States. Southern Med. J. 95:875–884, 2002.
Doorschodt, B., M. Schreinemachers, M. Behbahani, S. Florquin, J. Weis, M. Staat, and R. Tolba. Hypothermic machine perfusion of kidney grafts: which pressure is preferred? Ann. Biomed. Eng. 39:1051–1059, 2011.
Feng, C.-P., L.-B. Chen, G.-L. Tian, S.-S. Wan, L. Bai, R.-Y. Bao, Z.-Y. Liu, M.-B. Yang, and W. Yang. Multifunctional thermal management materials with excellent heat dissipation and generation capability for future electronics. ACS Appl. Mater. Interfaces. 11:18739–18745, 2019.
Gannon, M. Miniaturization Makes Pneumatics the Choice in Medical Applications. 2014.
Goldberg, D., B. French, P. Abt, and R. Gilroy. Increasing the number of organ transplants in the United States by optimizing donor authorization rates. Am. J. Transpl. 15:2117–2125, 2015.
Guibert, E. E., A. Y. Petrenko, C. L. Balaban, A. Y. Somov, J. V. Rodriguez, and B. J. Fuller. Organ preservation: current concepts and new strategies for the next decade. Transf. Med. Hemotherapy. 38:125–142, 2011.
Hicks, M., A. Hing, L. Gao, J. Ryan, and P. S. MacDonald. Organ preservation. Transpl Immunol. 13:331–373, 2006.
Hosgood, S. A., B. Yang, A. Bagul, I. H. Mohamed, and M. L. Nicholson. A comparison of hypothermic machine perfusion versus static cold storage in an experimental model of renal ischemia reperfusion injury. Transplantation. 89:830–837, 2010.
Hostetler, S. G., L. Schwartz, B. J. Shields, H. Xiang, and G. A. Smith. Characteristics of pediatric traumatic amputations treated in hospital emergency departments: United States, 1990–2002. Pediatrics. 116:e667–e674, 2005.
Houtzager, J. H., S. D. Hemelrijk, I. C. Post, M. M. Idu, F. J. Bemelman, and T. M. van Gulik. The use of the oxygenated AirdriveTM machine perfusion system in kidney graft preservation: a clinical pilot study. Eur. Surg. Res. 61:153–162, 2020.
Jing, L., L. Yao, M. Zhao, L. Peng, and M. Liu. Organ preservation: from the past to the future. Acta Pharmacol Sin. 39:845–857, 2018.
Kaminski, J., P. Delpech, S. Kaaki-Hosni, X. Promeyrat, T. Hauet, and P. Hannaert. Oxygen consumption by warm ischemia-injured porcine kidneys in hypothermic static and machine preservation. J. Surg. Res. 242:78–86, 2019.
Kirnap, M., and M. Haberal. Organ preservation. Transplantation surgery. New York: Springer, pp. 89–102, 2021.
Lloyd, M., T. Teo, M. Pickford, and P. Arnstein. Preoperative management of the amputated limb. Emerg. Med. J. 22:478–480, 2005.
Mazzantini, L., M. Dimitri, F. Staderini, F. Cianchi, and A. Corvi. Design and realization of a normothermic perfusion system for laboratory tests on pig liver. Int. J. Artif. Organs. 43:3–9, 2020.
Nowadly, C., D. J. Portillo, M. Davis, L. Hood, and R. De Lorenzo. The use of portable oxygen concentrators in low-resource settings: a systematic review. Prehospital Disaster Med. 37:247–254, 2022.
O’Callaghan, J., K. Pall, and L. Pengel. Supplemental oxygen during hypothermic kidney preservation: a systematic review. Transpl. Rev. 31:172–179, 2017.
OCS Liver Information. https://www.transmedics.com/ocs-hcp-liver/.
Patel, S., O. Pankewycz, N. Nader, M. Zachariah, R. Kohli, and M. Laftavi. Prognostic utility of hypothermic machine perfusion in deceased donor renal transplantation. Transpl. Proc. 44:2207–2212, 2012.
Patel, K., T. B. Smith, D. A. Neil, A. Thakker, Y. Tsuchiya, E. B. Higgs, N. J. Hodges, A. R. Ready, J. Nath, and C. Ludwig. The effects of oxygenation on ex vivo kidneys undergoing hypothermic machine perfusion. Transplantation. 103:314–322, 2019.
Petrenko, A., M. Carnevale, A. Somov, J. Osorio, J. Rodríguez, E. Guibert, B. Fuller, and F. Froghi. Organ Preservation into the 2020s: the era of dynamic intervention. Transf. Med. Hemotherapy. 46:151–172, 2019.
Pinezich, M., and G. Vunjak-Novakovic. Bioengineering approaches to organ preservation ex vivo. Exp. Biol. Med. 244:630–645, 2019.
Portillo, D. J., L. Bayliss, S. Rivas, G. Pineda, S. Kaur, L. Bunegin, and R. L. Hood. Characterizing and tuning perfusion parameters within an innovative, versatile oxygenating perfusion system. Ann. Biomed. Eng. 49:1–11, 2021.
Portillo, D. J., E. N. Hoffman, M. Garcia, E. LaLonde, E. Hernandez, C. S. Combs, and L. Hood. Modal Analysis of a Sweeping Jet Emitted by a Fluidic Oscillator. AIAA AVIATION 2021 FORUM. 2835, 2021.
Post, I. C., M. C. Dirkes, M. Heger, R. Bezemer, J. van’t Leven, and T. M. van Gulik. Optimal flow and pressure management in machine perfusion systems for organ preservation. Ann. Biomed. Eng. 40:2698–2707, 2012.
Rana, A., A. Gruessner, V. G. Agopian, Z. Khalpey, I. B. Riaz, B. Kaplan, K. J. Halazun, R. W. Busuttil, and R. W. Gruessner. Survival benefit of solid-organ transplant in the United States. JAMA Surg. 150:252–259, 2015.
Ravaioli, M., V. De Pace, A. Angeletti, G. Comai, F. Vasuri, M. Baldassarre, L. Maroni, F. Odaldi, G. Fallani, and P. Caraceni. Hypothermic oxygenated new machine perfusion system in liver and kidney transplantation of extended criteria donors: first Italian clinical trial. Sci. Rep. 10:1–11, 2020.
Tay, T.-T., I. Mareels, and J. B. Moore; High performance control; Springer Science & Business Media; 1998, pp.
Urbanellis, P., M. Hamar, J. M. Kaths, D. Kollmann, I. Linares, L. Mazilescu, S. Ganesh, A. Wiebe, P. M. Yip, and R. John. Normothermic ex vivo kidney perfusion improves early DCD graft gunction compared with hypothermic machine perfusion and static cold storage. Transplantation. 104:947–955, 2020.
U.S. Department of Health and Human Services. Organ Procurement and Transplantation Network, National Data. 2020.
van Suylen, V., K. Vandendriessche, A. Neyrinck, F. Nijhuis, A. van der Plaats, E. K. Verbeken, P. Vermeersch, B. Meyns, M. A. Mariani, and F. Rega. Oxygenated machine perfusion at room temperature as an alternative for static cold storage in porcine donor hearts. Artif. Organs. 46:246–258, 2022.
Xu, J., J. E. Buchwald, and P. N. Martins. Review of current machine perfusion therapeutics for organ preservation. Transplantation. 104:1792–1803, 2020.
XVIVO Perfusion System (XPS) Summary of Safety and Effectiveness Data. 2019.
Yuan, X., A. J. Theruvath, X. Ge, B. Floerchinger, A. Jurisch, G. García-Cardeña, and S. G. Tullius. Machine perfusion or cold storage in organ transplantation: indication, mechanisms, and future perspectives. Transpl. Int. 23:561–570, 2010.
Zimrin, T., Y. F. Haruvy, and S. Margel. High-resolution measurements of water permeability and solubility in microelectronic-casing made of a hydrophobic polymeric composite. J. Appl. Polym. Sci. 102:4523–4527, 2006.
Acknowledgments
This work was funded through a Department of Defense PRMRP; Award Number: W81XWH-18-1-0640. The authors would like to thank Dr. Ender Finol and Dr. Christopher Combs for providing data collection equipment and David Kuenstler for assisting with the fabrication of the VOPS.
Conflict of interest
This team has filed for a provisional patent that includes the design and operation of the device described in this study.
Author information
Authors and Affiliations
Corresponding author
Additional information
Associate Editor Emmanuel Opara oversaw the review of this article.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Portillo, D.J., Gonzalez, J., Villarreal, C. et al. Development and Characterization of a Nonelectronic Versatile Oxygenating Perfusion System for Tissue Preservation. Ann Biomed Eng 50, 978–990 (2022). https://doi.org/10.1007/s10439-022-02977-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10439-022-02977-2