Perfusion bioreactors for cardiovascular tissue engineering

V. Kasyanov, J. J. Sistino, T. C. Trusk, R. R. Markwald, V. Mironov

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Citation (Scopus)

Abstract

Since the discovery of the circulation by William Harvey, it has become clear that medical research would eventually employ artificial perfusion systems for the ex vivo study of living organs. As early as the 19th century, perfusion systems were used for physiological studies. However, there were significant technical limitations including the inability to prevent infection, and the lack of adequate blood oxygenators and blood pumps. In 1929, Alexis Carrel of the Rockefeller Institute began working on organ preservation. Together with Charles Lindbergh, who worked in Carrel's lab as a laboratory assistant, they made the major contributions to the development of organ perfusion systems. They constructed a complete pump-oxygenator apparatus for organ perfusion. Lindbergh's pump-oxygenator used compressed air, which was pulsed across cotton to maintain sterile conditions. The pulsating air oxygenated the blood as it circulated through the organ. The Lindbergh-Carrel apparatus is on display in the Smithsonian Institution of Technology in Washington D.C., and at the University of Florida where there is a collection carefully maintained by Professor Theodor Malinin. The textbook, "Culture of Organs" by Carrel and Lindbergh, which was published in 1939, has been inspiration for many generations of biomedical researchers. During the same time period, a student and future world-renowned cardiothoracic surgeon, Michael DeBakey, designed a roller pump for use in ex vivo perfusion. Also, John Gibbon began to develop during this same time period a heart and lung machine for use as a clinical device during heart surgery. The death of a young patient in 1931 had stirred Dr. Gibbon's imagination about developing an artificial device for bypassing the heart and lungs. Many others with whom he broached the subject dissuaded him, but he continued his experiments independently. In 1935 he successfully used a prototype heart-lung bypass machine to keep a cat alive for 26 minutes. John Gibbon joined forces with Thomas Watson in 1946. Watson was an engineer and the chairman of IBM (International Business Machines). He provided the financial and technical support for Gibbon to further develop his heart-lung machine. Later, Dr. John Gibbon performed the first successful human open heart operation on May 6, 1953 using this device. Thus began a new era surgical repair of the heart utilizing cardiopulmonary bypass. The Lindbergh-Carrel perfusion apparatus was used for a classic experiment in which a melanoma tumor was implanted in an isolated perfused rabbit thyroid gland. This experiment was performed by a young navy surgeon Judah Folkman, (Judah Folkman, personal communication). Folkman demonstrated that without an adequate vascular supply, the melonoma tumor implanted in the perfused thyroid gland stopped its growth. This was the foundation for the discovery of angiodependency of tumor growth. The eventual isolation and identification multiple angiogenic growth factors and inhibitors of angiogenesis led to the development of the concept of antitumor antiangiogenic therapy (Folkman, 1971). Tissue engineering has reactivated interest to perfusion systems. Mechanical conditioning is a powerful stimulator for tissue growth, deposition of extracellular matrix, and tissue remodeling (Kim et al., 1999; Niklason et al., 1999, Nerem and Seliktar, 2002; Mironov et al., 2003). The first successful clinical use of tissue engineered vascular grafts stimulated an urgent need to develop clinically acceptable perfusion bioreactors (Hibino et al., 2002; Naito et al., 2003). The recent development of organ printing (Mironov et al., 2003), opens a new phase in cardiovascular tissue engineering research which will require designing perfusion bioreactors to maintain the entire heart. The goal of this review is: i) to describe the original perfusion bioreactor for vascular tissue engineering with capacities for longitudinal stretch; ii) to discuss the special requirements for next generation of perfusion bioreactors for 3D vascularized tissue engineered myocardial tissue and the printed tissue engineered heart; and iii) to review some emerging (on different stage of development) industrial perfusion systems which could be adapted for experimental, industrial and clinical cardiovascular tissue engineering. Perfusion bioreactors for tissue engineered heart valves and clinical perfusion systems, which are used routinely in cardiothoracic surgery, are outside the scope of this review.

Original languageEnglish
Title of host publicationBioreactors for Tissue Engineering
Subtitle of host publicationPrinciples, Design and Operation
PublisherSpringer Netherlands
Pages285-307
Number of pages23
ISBN (Print)1402037406, 9781402037405
DOIs
Publication statusPublished - 2005
Externally publishedYes

Field of Science

  • 2.6 Medical engineering

Publication Type

  • 3.1. Articles or chapters in proceedings/scientific books indexed in Web of Science and/or Scopus database

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