Tissue Engineering: Applications, Techniques, and Future Potential

Introduction to Tissue Engineering

Tissue engineering is an interdisciplinary field that utilizes the principles of life sciences and engineering for the creation of biological substitutes or replacements that can heal, improve, maintain, or restore the functions of tissues. It involves contributions from doctors, chemical engineers, cell biologists, chemists, and materials scientists. Since it is a comparatively new field, tissue engineering faces various challenges ahead (Shoseyov & Levy, 2007).

Tissue engineering can be used to manufacture whole tissues in vitro, or outside the body. These manufactured tissues can then be used for transplant, for the repair and regeneration of various connective tissue structures such as bone and cartilage, and for the replacement of skin. Tissue engineering can offer treatment for various diseases such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, diabetes, kidney disease, chronic heart disease, liver failure, and cancer. It can also be used for gene therapy. It is estimated that the worldwide market for tissue engineering products will be worth around $5 billion in the coming years, with future projections placing that figure at more than $10 billion by 2013 ("Tissue Engineering and Stem Cell Technology Report 2007," 2007).

The tissue engineering process involves growing a network of cells outside the body to form fully functional tissues. The initial group of cells may be obtained from donors or from the patients in whom transplantation is to be performed. This could make many severe medical conditions perfectly curable. For instance, an artificial pancreas grown in the laboratory using tissue engineering techniques and transplanted into a patient could make Type I diabetes perfectly curable (Gazit, 2006).

Fabrication Techniques: Biological Printing and Bionanotechnology

One way in which tissue can be manufactured in vitro is through a "biological printing" technique. This technique involves the deposition of proteins on various surfaces in the form of microscopic patterns. Several chunks of clear silicone rubber with an array of microscopic lines imprinted on them are arranged in a Petri dish. Next, a liquid containing fibronectin — a common protein — is applied onto each "stamp." As it dries on the silicone surface, a thin layer of this protein is formed. Each stamp is then pressed onto a round glass coverslip that is also silicone-coated. The proteins on the raised portions of the microscopic array are transferred onto the silicone film of the coverslip in a similar pattern. This process is repeated with every stamp.

The coverslips are then immersed in a solution of young, developing cells of the target tissue harvested from the donor. These cells adhere to the fibronectin in organized lines. The entire solution, containing the coverslips and cells, is placed in an incubator. Over the next few days, the young cells slowly begin developing along the protein lines. These lines aid in cell alignment; without them, cells would clash with each other as they developed in a disorganized manner (Bullis, 2008).

The new tissue is removed from the incubator and, upon cooling, the temperature-sensitive adhesive binding the silicone to the glass coverslip begins to melt. The tissue can then be cut into appropriate shapes. Using this technique, researchers have been able to grow heart tissues and use them to screen the effects of various drugs on cardiac contraction. The technique could also be used to produce muscle cells that line arteries and veins, and to test the effects of hypertension drugs. Even smaller devices could be fabricated from these tissues for use as implantable robots inside the human body (Bullis, 2008).

Another technology being used to engineer tissues is bionanotechnology. One major advantage of this approach is that the patient's own cells can be used to fabricate the artificial tissue, effectively addressing the issue of organ rejection, since the new tissue would share the same immunological characteristics as the patient's own tissue. Tissue engineering with the help of nanotechnology involves the manufacture of a "smart matrix" on a nano-scale, containing signals for the growth and differentiation of cells. The matrix provides a scaffold framework for the systematic arrangement of embryonic or adult stem cells and supplies them with an optimum environment for the growth of the engineered tissue.

An important property of stem cells is their capability to differentiate into diverse tissues with different morphology, sensory abilities, functions, and synthetic capabilities. Research has suggested that the application of external electrical stimuli can effectively control the process of organ formation. One particularly important application is the engineering of brain tissue. Approximately 4 million Americans were affected by Alzheimer's disease in 2006, and tissue engineering may offer a ray of hope in this area (Gazit, 2006). Recent advances in the field also include three-dimensional (3D) cell culture, which more closely replicates the natural body environment compared to the conventional two-dimensional (2D) approach. This 3D approach is especially advantageous for certain organ systems, such as the heart (Petersen, Lazar, Jacob, & Wakatsuki, 2007).

Clinical Applications in Organ and Tissue Repair

Another major health problem affecting a large number of individuals is bone defects caused by trauma or tumors. These can be addressed by supporting the natural healing and development processes with tissue engineering. Bone tissue engineering mimics natural bone formation by combining stem cells, growth factors, and differentiation factors on appropriate scaffolds in a regulated manner.

Tissue engineering also holds promise for those suffering from liver disease. Unlike the kidneys and lungs, the liver does not occur in pairs, and its failure is therefore often life-threatening. There is also a dire shortage of donor livers. Bioartificial livers can be used to sustain patients until a donor liver becomes available. The components of a bioartificial liver include: (i) a bioreactor — a structure consisting of a cell compartment with hollow channels connected to it for the supply of gases and essential nutrients; (ii) cells mimicking liver tissue inside the cell compartment; and (iii) a microenvironment composed of growth factors, a nutrient medium, serum supplements, hormones, and extracellular matrix or scaffolding material (Atala, 2007).

A major challenge for clinicians is the repair of the damaged human retina, which has a limited capacity for self-repair or regeneration. Tissue engineering involving stem cells or progenitor cells from various parts of the central nervous system (CNS) may prove to be an effective therapy for retinal degeneration. CNS stem cells not only possess the capability for self-renewal but also carry a reduced risk of immunologic rejection due to their intrinsic immune status (Tombran-Tink & Barnstable, 2007).

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