Artificial organs

Summary

Artificial organs are complex systems of natural or manufactured materials used to supplement failing organs while they recover, sustain failing organs until transplantation, or replace failing organs that cannot recover. Some whole organs have artificial counterparts: heart, kidneys, liver, lungs, and pancreas. Smaller body parts also have artificial counterparts: blood, bones, heart valves, joints, skin, and teeth. In addition, there are mechanical support systems for circulation, hearing, and breathing. Artificial organs are composed of biomaterials, biological or synthetic materials that are adapted for use in medical applications.

Definition and Basic Principles

Artificial organs are complex systems that assist or replace failing organs. The human body is composed of ten major organ systems: nervous, circulatory, respiratory, digestive, excretory, reproductive, endocrine, integumentary (skin), muscular, and skeletal. The nervous system transmits signals between the brain and the body via the spinal cord and nerves. The circulatory system transports blood to deliver oxygen and nutrients to the body and to remove waste products. Its organs are the heart, blood, and blood vessels. It works closely with the respiratory system, in which the lungs and trachea perform oxygen exchange between the body and the environment. The digestive system breaks down food and absorbs its nutrients. Its organs include the esophagus, stomach, intestinal tract, and liver. The excretory system rids the body of metabolic waste in the form of urine and feces. The reproductive system provides sex cells and, in females, the organs to develop and carry an embryo to term. The endocrine system consists of the pituitary, parathyroid, and thyroid glands, which secrete regulatory hormones. The integumentary system is the body's external protection system. Its organs include skin, hair, and nails. The muscular system recruits muscles, ligaments, and tendons to move the parts of the skeletal system, which consists of bones and cartilage.

Background and History

While he was still a medical student in 1932, renowned cardiac surgeon Michael DeBakey introduced a dual-roller pump for blood transfusion. It has since become the most widely used type of clinical pump for cardiopulmonary bypass and hemodialysis. Physician John H. Gibbon, Jr., of Philadelphia, developed the first clinically successful heart-lung pump. He initially demonstrated it in 1953 when he closed a hole between the atria of an eighteen-year-old girl.

In 1954, American physician Joseph Murray performed the first successful human kidney transplant from one identical twin to the other in Boston. In 1962, he performed the first kidney transplant in unrelated persons. In 1967, surgeon Christiaan Barnard performed the first successful human heart transplant in Cape Town, South Africa. The patient, a fifty-four-year-old man, lived another eighteen days.

Physician Willem J. Kolff is considered to be “the father of the artificial organ.” In 1967, he emigrated from the Netherlands and spent a good deal of his career at the University of Utah, where he became a distinguished professor emeritus of internal medicine, surgery, and bioengineering. He led the designing of numerous inventions, including the modern kidney dialysis machine, the intra-aortic balloon pump, an artificial eye, an artificial ear, and an implantable mechanical heart.

American physician Robert K. Jarvik refined Kolff's design into the Jarvik-7 artificial heart, intended for permanent use. In 1982, at the University of Utah, American surgeon William C. DeVries implanted it into retired dentist Barney Clark, who survived 112 days. Artificial hearts would eventually be approved for widespread use, though the installation of an artificial heart was usually considered inferior to a heart transplant.

How It Works

The existence and performance of artificial organs depend on the collaboration of scientists, engineers, physicians, manufacturers, and regulatory agencies. Each of these groups provides a different perspective on pumps, filters, size, packaging, and regulation.

Hemodynamics. The human heart acts as a muscular pump that beats an average of seventy-two times a minute. Each of the two ventricles pumps 70 milliliters of blood per beat or 5 liters per minute. Blood pressure is measured and reported as two numbers: the systolic pressure exerted by the heart during contraction and the diastolic pressure when the heart is between contractions. Hemodynamics is the study of forces related to the circulation of the blood. The hemodynamic performance of artificial organs must match that of the natural body to operate efficiently without resulting in damage. Calculations may be made using computational fluid dynamics (CFD); relevant parameters include solute concentration, density, temperature, and water concentration. In addition to artificial hearts, which are intended to perform all cardiac functions, there is a mechanical circulatory implement called a ventricular assist device (VAD) that supports the function of the natural heart while it is recovering from a heart attack or surgery. Its pumping action may be pulsatile, in rhythmic waves matching those of the beating heart, or continuous.

Mass Transfer Efficiency. The human kidney acts as a filter to remove metabolic waste products from the blood. A person's kidneys process about 200 quarts of blood daily to remove two quarts of waste and extra water, which are converted into urine and excreted. Without filtration, the waste would build to a toxic level and cause death. Patients with kidney failure may undergo dialysis, in which blood is withdrawn, cleaned, and returned to the body in a periodic, continuous, and time-consuming process that requires the patient to remain relatively stationary. Portable artificial kidneys, which the patient wears, filter the blood while the patient enjoys the freedom of mobility. Filtration systems may involve membranes with a strict pore size to separate molecules based on size or columns of particle-based adsorbents to separate molecules by chemical characteristics. Mass transfer efficiency refers to the quality and quantity of molecular transport.

Scale. The development of artificial organs requires that biological processes that can be duplicated in the laboratory be scaled up to work within the human body without also magnifying the weaknesses. Biological functions occur at the organ, tissue, cellular, and molecular levels, which are on micro- and nanoscales. In addition, machines that work in the engineering laboratory must be scaled down to work within the human body without crowding the other organs. Novel power sources and electronic components have facilitated miniaturization. Size must also be balanced with efficiency and cost. Computer-aided design software is being used to create virtual three-dimensional models before fabrication.

Biomaterials. Artificial organs are made of natural and/or manufactured materials that have been adapted for medical use. The properties of these materials must be controlled down to the nanometer scale. The biological components may serve in gene therapy, tissue engineering, and the modification of physiological responses. The synthetic materials must be biocompatible, which means that they do not trigger an adverse physiological reaction such as blood clotting, inflammatory response, scar-tissue formation, or antibody production. The biomechanics of the artificial organ, such as friction and wear, must be known, and parts must be sterile before use. Biomaterials have been developed for subspecialties such as orthopedics and ophthalmics.

Regulation. The body has natural feedback systems that allow the exchange of information with the brain for optimal regulation. Artificial organs that communicate directly with the brain are still in development. The present models require sensors and data systems that may be monitored by physicians. Implanted devices must be able to be inspected without direct observation. Another aspect of regulation is the uniform manufacturing of artificial organs in compliance with performance and patient safety specifications.

Applications and Products

The collective knowledge of scientists, engineers, physicians, manufacturers, and regulatory agencies has produced the applications and products in the interdisciplinary realm of artificial organs.

Hemodynamics. Knowledge of hemodynamics, the study of blood-flow physics, has led to the development of artificial circulatory assistance. The ventricular assist device (VAD) supplements the contraction of the two lower chambers of the heart, so the heart muscle does not have to work as hard while it is healing. The cardiopulmonary bypass pump, also known as a heart-lung machine, provides blood oxygenation and circulating pressure during open-heart surgery when the heart is stopped. A similar application called extracorporeal membrane oxygenation (ECMO) is used to assist neonates and infants in the intensive care unit and to maintain the viability of organs pending transplantation. The natural pressure generated by a healthy heart is used to send blood through versions of artificial lungs and kidneys without batteries.

Mass Transfer Efficiency. Information about molecular transport and delivery, known as mass transfer efficiency, has been applied to the separation and secretion functions of artificial organs. In hemodialysis, toxins are removed from circulating blood that passes through a filter called a dialyzer. This process also removes excess salts and water to maintain a healthy blood pressure. The dialyzer is composed of a semipermeable membrane or cylinder of hollow synthetic fibers that separates out the metabolic-waste solutes in the incoming blood by diffusion into dialysate solution, leaving cleaner outgoing blood. Hemofiltration is a similar process; however, the filtration occurs without dialysate solution because instead of diffusion, the solutes are removed more quickly by hydrostatic pressure. Another separation technique in medical applications is apheresis, in which the constituents of blood are isolated. This may be achieved by gradient density centrifugation or absorption onto specifically coated beads. The therapeutic application is the absorptive removal of a specific blood component that is causing an adverse reaction in a patient, with the remaining components returned to the patient's circulatory system. The pathogenic blood component might be malignant white blood cells, excess platelets, low-density lipoprotein, autoantibodies, or plasma. The second application of apheresis is the separation of components following blood donation. Concentrated red blood cells are administered in the treatment of sickle-cell crisis or malaria. Plasmapheresis is used to collect fresh frozen plasma as well as rare antibodies and immunoglobulins.

Scale. Miniaturization of artificial organs has been facilitated by the application of smaller, more efficient batteries, transistors, and computer chips. For example, hearing aids once had to be worn with cumbersome amplifiers and batteries disguised in a purse or camera case with a carrying strap. Existing models fit completely in the ear canal, and a computer chip facilitates digital rather than analogue processing for crisper sound. The artificial kidney has evolved into a wearable model that weighs 10 pounds and is seventeen times smaller than a conventional dialysis machine. Its hollow-fiber filter must be replaced once a week, and its dialysate solution must be replenished daily. However, this maintenance is a trade-off that many patients are willing to make for freedom of movement. On the horizon is an artificial retina that depends on a miniature camera to transmit images. Conversely, research is underway to produce large-scale cultures of tissues on biohybrid matrices and scaffolding for transplantation.

Biomaterials. Synthetic materials are used in artificial organs. Dacron (polyethylene terephthalate) is a polyester fiber with high tensile strength and resistance to stretching, whether wet or dry, chemical degradation, and abrasion. Patches of it are sewn to arteries to repair aneurysms. When tubing of it is used as an aortic valve bypass, the patient will not require subsequent blood-thinning medications. Gore-Tex (expanded polytetrafluoroethylene) is an especially strong microporous material that is waterproof. Vascular grafts made from it are supple and resist kinks and compression. It is also used for replacing torn anterior and posterior cruciate ligaments in the knee.

Perfluorocarbon fluids are synthetic liquids that carry dissolved oxygen and carbon dioxide with negligible toxicity, no biological activity, and a short retention time in the body. These features make them ideal for medical applications. One of these fluids, perfluorodecalin, is typically used as a blood substitute (also called a blood extender) because it mixes easily with blood without changing the hemodynamics. It increases the oxygen-carrying capacity of the blood and penetrates ischemic (oxygen-deprived) tissues especially easily because of its small particle size. This makes it particularly useful in the healing of ulcers and burns. It is also used in conjunction with ECMO in the life support of preterm infants to increase oxygenation and to keep the lungs inflated, reducing exertion. Furthermore, it is used in the preservation of harvested organs and cultured tissue for transplantation, extending their viable storage time.

Regulation. The application of regulatory systems has allowed artificial organs to be adjusted while they are in use. Artificial cardiac pacemakers, which supplement the natural electrical pacemaking capabilities of the heart to normalize a slow or irregular heartbeat, are externally programmable so that cardiologists are able to establish the optimal pacing parameters for each patient. Adjustments are made with radio frequency programming, so no further surgery is required. Contemporary hearing aids have volume controls that the wearer can adjust to suit changing surroundings. The inability to detect high- or low-pitch sounds is not a function of volume, yet pitch range can be adjusted in a hearing aid by an audiologist. Other parameters are also adjustable, and the audiologist can reprogram the hearing aid as a person's hearing loss changes.

Careers and Course Work

Universities offer various undergraduate and graduate programs related to artificial organs. The University of Pittsburgh's Swanson School of Engineering offers undergraduate degrees in bioengineering with concentration choices of cellular and medical product engineering, biomechanics, and biosignals and imaging. Brown University's Department of Molecular Pharmacology, Physiology, and Biotechnology offers master's and doctoral degrees in artificial organs, biomaterials, and cellular technology.

Medical schools support researchers in the field of biotechnology development. Some schools have specialized programs or facilities, such as the Artificial Organs Laboratory at the University of Maryland School of Medicine's Department of Surgery. This is a collaborative field, and scientists, biomedical engineers, physicians, and businesspeople work together in commercial ventures to design and fabricate functional artificial organs. Because artificial organs fall under the regulatory domain of the Food and Drug Administration (FDA) as medical devices, manufacturers must undergo rigorous product development, clinical trials, and patent protection prior to FDA approval. Components are then made to custom specifications. Some companies produce a multitude of medical devices, while some specialize in specific technologies such as biotransport, dialysis, perfusion, and cell culture matrices.

Social Context and Future Prospects

The number of Americans older than sixty-five years of age has increased steadily and was expected to continue to grow into the mid-twenty-first century. The increasing life span of the general population drives greater demand for organ replacement, and a shortage of donor organs exacerbates the situation. For example, each year, the number of people waiting for kidney transplants greatly exceeds the number of available kidneys. Therefore, the need for artificial organs as a bridge to transplantation or even as a permanent substitute for failed organs is becoming increasingly urgent.

Once only made of synthetic components, artificial organs are becoming biohybrid organs: a combination of biological and synthetic components. Examples include functionally competent cells enveloped within immuno-protective artificial membranes and tissues cultured on chemically constructed matrices. Experiments are underway to develop an antibacterial agent that can be incorporated into biomaterials to reduce the risk of infection from these organ surfaces. Emerging technologies also involve sensors and intelligent control systems, biological batteries and alternate power sources, and innovative delivery systems.

Other research areas include the miniaturization of artificial organs for pediatric use and the development of smaller and more efficient batteries and sensors capable of more accurate communication between the artificial organ and the brain. Another goal is to incorporate wireless capabilities so the artificial organ may be programmed, monitored, and recharged remotely so the patient has increased freedom of mobility. Several other areas of research exist and are expanding as well. The ability to 3D print artificial organs has allowed artificial organs to contain more customizable components. New types of materials for artificial organs are also being developed. Artificial organs that can repair themselves through regeneration are also becoming a reality through stem cell technology. Finally, implementing Artificial Intelligence in artificial organs has aided devices in becoming more innovative and intuitive following transplants. The scientific and medical community continues to innovate the field of artificial organs through new techniques, materials, and technology. 

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