Cell and Tissue Engineering

Summary

Cell and tissue engineering are fields dedicated to discovering the mechanisms that underlie cellular function and organization to develop biological or hybrid biological and nonbiological substitutes to restore or improve cellular tissues. The most immediate goal of cell and tissue engineering is to allow physicians to replace damaged or failing tissues within the body. The field was first recognized as a distinct branch of bioengineering in the 1980s and has since grown to attract participation from numerous medical and biological disciplines.

Engineered cellular materials may be used to grow new tissue within a patient's heart or to replace damaged bone, cartilage, or other tissues. In addition, research into the mechanisms affecting cellular organization and development may aid in the treatment of congenital and developmental disorders. Cell and tissue engineering has developed in conjunction with stem cell research and is, therefore, subject to debate over the ethics of stem cell research.

Definition and Basic Principles

Cell and tissue engineering is a branch of bioengineering concerned with two basic goalsstudying and understanding the processes that control and contribute to cell and tissue organization and developing substitutes to replace or improve existing tissues in an organism. Substitute tissues can be composed either of biological materials or a blend of biological and non-biological materials.

The basic goal of cell and tissue engineering is to create more effective treatments for tissue degeneration and damage resulting from congenital disorders, disease, and injury. Engineers may, for instance, introduce foreign tissues that have been modified to stimulate healing within the patient's own tissues, or they may implant synthetic structures that help control and stimulate cellular development. Another goal in cell and tissue engineering is to create tissues that are resistant to rejection from the host organism's immune system. Rejection is one of the primary difficulties in organ transplantation and limb replacement surgery.

One of the basic principles of cell and tissue engineering is to use and enhance an organism's innate regenerative capacity. Engineers examine the ways that tissues grow and change during development. Using cutting-edge developments in genomics and gene therapy, engineers work to develop ways to stimulate a patient's immune system and enhance healing.

Cell and tissue engineering have a wide variety of potential applications. In addition to creating new therapies, engineering principles can be used to create new methods for delivering drugs and engineered cells to target locations within a patient. The potential applications of cell and tissue engineering depend on the capability to create cultures of cells and tissues to use for experimentation and transplantation. Research on cell growth is a major facet of the bioengineering field.

Background and History

Cell and tissue engineering emerged from a field of study known as regenerative medicine, a branch concerned with developing and using methods to enhance the regenerative properties of tissues involved in the healing process. Ultimately, cell and tissue engineering became most closely associated with transplant medicine and surgery.

Medical historians have found documents from as early as 1825 recording the successful transplantation of skin. The first complete organ transplants occurred in the 1950s, and the first heart transplant was completed successfully in 1964.

The science of cell and tissue engineering arose from attempts to combat the problems that affect transplantation, including scarcity of organs and frequent issues involving rejection by the host's immune system. In the 1970s and 1980s, scientists began working on ways to build artificial or semi-artificial substitutes for organ transplants. Most early work in tissue engineering involved the search for a suitable artificial substitute for skin grafts.

By the mid-1980s, physicians were using semi-synthetic compounds to anchor and guide transplanted tissues. The first symposium for tissue engineering was held in 1988, by which time the field had adherents around the world. The rapid advance of research into the human genome and genetic medicine in the mid-1990s had a considerable effect on bioengineering. In the twenty-first century, cell and tissue engineers work closely with genetic engineers in an effort to create new and better tissue substitutes.

How It Works

Broadly speaking, cell and tissue engineering involves creating cell cultures and tissues that are introduced to an organism to repair damaged or degenerated tissues. There are a wide variety of techniques and specific applications for cell and tissue engineering, ranging from cellular manipulation at the chemical or genetic level to the creation of artificial organs for transplant.

Most cell and tissue engineering methods share several common procedures. First, scientists must produce cells or tissues. Next, engineers must tell the cells what to do. This can be done in a variety of ways, from physically manipulating cellular development and tissue formation to altering the genes of cells in such a way as to direct their function. Finally, engineered tissues and cells must be integrated into the body of the host organism under controlled conditions to limit the potential for rejection. Cell and tissue engineering can be divided into two main categories, in vitro engineering and in vivo engineering.

In Vitro Engineering. In vitro engineering is the development of cell cultures and tissues outside of the body in a controlled laboratory environment. This method has several advantages. Producing tissues in a laboratory has the potential for growing large amounts of tissue and, eventually, entire organs. This could help solve a major issue with transplant surgery—the scarcity of viable organs for transplantation. Scientists can more precisely control the growing environment and can exert greater control over developing cells and tissues. In vitro engineering allows engineers to modify and adjust cellular properties without the need for surgery or invasive techniques.

In vitro engineering is commonly used in the creation of skin tissues, cartilage, and some bone replacement tissues. Although in vitro techniques have certain advantages, they have serious drawbacks, including a higher rejection rate for cells and tissues created in vitro. In addition, there are physiological advantages to engineering within the host organism's body, including the presence of accessible cellular nutrients.

In Vivo Engineering. In vivo engineering is the family of techniques that involves creating engineered cellular cultures or tissues within the host's body. It involves the use of chemicals to alter cellular function and the use of synthetic materials that interact with the host's body to stimulate or direct cellular growth.

In vivo procedures typically involve introducing only minor changes to the host's internal environment, and, therefore, these tissues are more likely to be resistant to rejection. In addition, working in vivo allows engineers to take full advantage of the host's existing cellular networks and the physiological environment of the body. The body provides the essential nutrients, exchange of materials, and disposal of waste, helping create healthy tissues.

The primary disadvantages of the in vivo approach are that engineers have less direct control over the development of the cells and tissues and cannot make exact changes to the microenvironment during development. In addition, in vivo engineering does not allow for the production of mass quantities of cells and is, therefore, not an avenue toward addressing the shortage of available tissues and organs for transplant.

Applications and Products

Hundreds of bioengineers are working around the world, and they have created a wide variety of applications using cell and tissue engineering research. Among the most promising applications are cell matrices and bioartificial organ assistance devices.

Cell Matrices. In an effort to improve the success of tissue transplants, bioengineers have developed a method for using artificial matrices, also called "scaffolds," to control and direct the growth of new tissues. Using cutting-edge microengineering techniques and materials, engineers create three-dimensional structures that are implanted into an organism and, thereafter, serve as a "guide" for developing tissues.

The scaffold acts like an extracellular matrix that anchors growing cells. New cells anchor to the artificial matrix rather than to the organism's own extracellular material, allowing engineers to exert control over the eventual size, shape, and function of the new tissue. In addition, scaffolds can aid in the diffusion of resources within the growing tissue and can help engineers direct the placement of functional cells, as the scaffold can be installed directly at the site of an injury.

Matrices may be constructed from a variety of materials, including entirely synthetic combinations of polymers and other structures that are created from derivatives of the extracellular matrix. Many researchers have been designing scaffolds that dissolve as the tissues form and are then absorbed into the organism. These biodegradable scaffolds allow engineers to avoid further surgical procedures to remove implanted material.

Cellular scaffolds represent a middle ground between in vivo and in vitro engineering. Engineers can create a scaffold in a laboratory environment and can allow tissue to anchor and grow around the matrix before implantation, or they can place a scaffold in their target area within the organism and allow the organism's own cells to populate the matrix.

Scaffolds have been used successfully in cardiac repair, especially with stem cells. A scaffold seeded with stem cells may be implanted directly into a heart valve, roughly at the site of a cardiac infarction. The scaffold then directs the growing cells toward the injured area and facilitates the regeneration of damaged tissue.

Artificial matrices have also successfully treated disorders affecting the kidney, bone, and cartilage. Researchers are hopeful that cellular scaffolds could eventually allow the creation of entire organs by coaxing cells to develop around a scaffold designed as an organ template.

Bioartificial Organs. One of the major areas of research in tissue engineering is the creation of machines that assist organs damaged by disease or injury. Made from a combination of synthetic and organic materials, these machines are sometimes called bioartificial devices.

One of the most promising organ assistance devices is the bioartificial liver (BAL), which was developed to help patients suffering from congenital liver disease, acute liver failure, and other metabolic disorders affecting the liver. The BAL consists of cells incorporated into a bioreactor, which is a small machine that provides an environment conducive to biological processes. Cells growing within the BAL receive optimal nutrients and are exposed to hormones and growth factors to stimulate development. The bioreactor is also designed to facilitate the delivery of any chemicals produced by the developing tissues to surrounding areas.

The BAL performs some of the functions usually performed by the liver. It processes blood, removes impurities, produces proteins, and aids in synthesizing digestive enzymes. The BAL is not intended to permanently replace the liver but rather to supplement liver function or to allow a patient to survive until a liver transplant can be arranged. The bioartificial liver enables patients to forgo dialysis treatments, and some researchers hope to develop BAL devices that may function as a permanent replacement for patients in need of dialysis.

Researchers are working on bioartificial kidney devices that would aid patients with diabetes and other disorders leading to kidney failure. Again, the bioartificial kidney devices are bioreactors, using stem cells and kidney cells to perform some of the purification and detoxification functions of the kidney. Researchers are also developing bioartificial devices to treat disorders of the pancreas and the heart and to help patients suffering from nervous system or circulatory disorders. Taken as a whole, the development of organ assistance devices may be a step toward the development of bioartificial devices that can function to fully replace a patient's malfunctioning organ.

Careers and Course Work

Students interested in cell and tissue engineering might start at the undergraduate level, working toward a biology or biochemistry degree focusing on cellular biology. They might also enter the bioengineering field with a background in engineering, though they will still need a significant background in biology and medical science.

After undergraduate education, students can progress by pursuing graduate studies in cell biology, bioengineering, or related fields. Many professionals working in other disciplines, such as orthopedic medicine, dermatology, and cardiac surgery, may also become involved with cell and tissue engineering during their careers. Graduate institutions are increasingly trying to introduce programs focusing on cell and tissue engineering. The University of Pittsburgh and Duke University offer specializations in tissue and cell engineering for qualified graduate candidates.

Professionals seeking cell and tissue engineering work can seek employment with nonprofit research institutions, such as those in many universities. A combination of public and private funds generally funds university positions. Additionally, those interested in bioengineering careers can find employment within many corporations. Hundreds of biotechnology companies in the United States employ chemists, mechanical engineers, physicians, and individuals explicitly trained in bioengineering.

Social Context and Future Prospects

Bioengineering is intended to improve daily life for the general population and those suffering from injury and illness. Cell and tissue engineers focus on ways to replace damaged tissues. They may engineer new skin tissue where the skin has been destroyed, such as Cell Therapy 2.0, or develop technology to supplement the function of essential organs. The industry aims to create artificial organs that can fully and permanently replace damaged organs. Bioengineers hope to provide patients with various organs, particularly the heart, liver, or pancreas, on which most research focuses.

Although most cell and tissue engineers focus on combating physical illness and injury, bioengineering also has the potential to produce technology that will allow humans to improve their functional abilities. Combinations of synthetic computer technology and biological components could improve human visual capacity or endow humans with more precise access to memory.

Humans are not the only targets for bioengineers, as other organisms may also be altered to improve their basic physiological functions. For example, in the early 2000s, the Australian Centre for Plant Functional Genomics researchers attempted to bioengineer plants to withstand higher salt levels in the soil. This breakthrough could turn into a major benefit for agriculture. Salt-resistant strains of important crops could grow where agriculture was previously impossible because of the soil's alkalinity. In the late 2010s, scientists at Brandeis University created a soft tissue that mimics the behavior of natural neural tissue. 

As a distinct discipline, bioengineering is relatively new, and scientists have only begun to unlock its potential. As the field expands, so too do opportunities for scientists, engineers, and physicians interested in exploring the future of medicine and science. Universities, hospitals, and biomedical corporations will likely increase their investment in these emerging technologies and techniques, creating a strong and growing industry. Research is trending toward precision medicine, machine learning-enabled drug discovery, new drug delivery methods, and revolutionary materials, such as self-repairing fabric.

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