Biomaterials Tutorial

Tissue Engineering

Stephanie J. Bryant
University of Colorado at Boulder

Tissue engineering can be defined as “an interdisciplinary field that applies the principles of engineering and the life sciences towards the development of biological substitutes that restore, maintain, or improve tissue function” [1, 2]. The success of tissue engineering relies on multidisciplinary teams that are comprised of cell biologists, material scientists, engineers, and clinicians. In tissue engineering, there are three basic strategies: (i) delivery of healthy cells directly to a tissue site to replenish a loss of cells, (ii) delivery of tissue-inducing molecules to stimulate host cells to function normally, and (iii) development of a 3D matrix or scaffolding material within which cells grow to create living 3D tissue substitutes.

Designing scaffolds to promote tissue growth has received a huge amount of focus in recent years. Scaffolds must be biodegradable and can be made from either natural or synthetic polymers. The purpose of the scaffold is to serve as a temporary support for growing cells to form new tissue around.  As the scaffold degrades, the end result consists of only cells and tissue.

In general there are several approaches to using scaffolds for tissue engineering. One approach is to fabricate a porous scaffold of defined shape and architecture onto which cells are seeded (see tutorial on Porous Scaffolds). The cell scaffold is placed in a tissue culture system to support growth, called a bioreactor. Once the 3D tissue equivalent has formed, the engineered tissue is surgically implanted into the host and fixed into place. Alternatively, the scaffold containing cells can be directly implanted, allowing the body to serve as the bioreactor. A third approach is to design a scaffold that forms when placed in the body, such as an injectable liquid that gels in situ.  The attractive feature of this process is that cells can be combined with a liquid solution and injected into the desired regions, creating a minimally invasive surgical procedure. Once injected, the liquid solidifies, encapsulating the cells within the scaffold.

Figure 1. Tissue engineering strategies utilizing 3D scaffolding materials. The patient’s own cells can be isolated, for example, from a small biopsy of healthy tissue (to obtain tissue specific cells) or from the patient’s bone marrow (to obtain mesenchymal stem cells). Once the cells are isolated, their numbers are expanded in vitro.  These cells can either be combined with a liquid solution and injected directly into the desired tissue site to form a 3D scaffold in situ that eventually degrades as the encapsulated cells grow new tissue (Strategy 1) or placed onto a 3D porous scaffold that is implanted directly or is first cultured in a bioreactor to create a living tissue equivalent that is surgically implanted into desired tissue site (Strategy 2).

Although the field of tissue engineering is less than 20 years old, a significant amount of progress has been made in a relatively short period of time. Nearly every tissue in the body is being investigated, including skin, cartilage, bone, nerves, blood vessels, heart valves, heart muscle, to name just a few examples. Engineered skin is the first tissue engineered product to becommercially available. Reconstruction of entire organs is also being investigated. Bladder reconstruction using tissue engineering strategies is currently in clinical trials [3]. More and more, tissue engineering strategies are being accepted as a resource for regenerating tissue

References:

1. Nerem, RM. Cellular Engineering. Ann Biomed Eng 1991; 19: 529-45.
2. Langer R, Vacanti JP. Tissue engineering. Science 1993; 260: 920-6.
3. Atala A. Tissue engineering and regenerative medicine: Concepts for clinical application. Rejuvenation Research 2004; 7: 15-31.

Further Reading

1. Lanza RP, Langer R, Vacanti JP. Principles of tissue engineering. San Diego: Academic Press, 2000.
2. Atala A, Lanza RP. Methods in tissue engineering. San Diego: Academic Press,  2002.
3. Palsson B, Hubbell JA, Plonsey R, Bronzino JD. Tissue engineering. In: Principles and Applications in Engineering. CRC Press, 2003.
4. Palsson B, Bhatia SN. Tissue engineering. Prentice Hall, 2003.
5. Saltzman WM. Tissue engineering: Principles for the design of replacement organs and tissues. Oxford University Press, 2004.