differentiate into several but not all cell types, have been in use for decades. Hematopoietic2 and mesenchymal3 stem cells are commonly used but have limited capacity. Primary cells, or terminally differentiated cells, lack the capacity to regenerate numerous times, and often cell quality decreases with each passage.

Today, most tissues are too complex to be replicated. First, the ability to create a vascularized tissue remains a fundamental challenge in the field. Mass-transport limitations governing nutrients and waste affect the function and viability of a tissue (Allen et al., 2001; Sachlos and Auguste, 2008). Microfluidic, capillary-like systems exhibit high resistance and require substantial pressures to produce continuous flow. Second, the ability to organize cells in three dimensions is limited. Hydrogel-based and scaffold-based matrices offer little help in the assembly of cellular networks, which are important for cell–cell communication. For example, the heart and muscles must contract synchronously. Discontinuities within the cell organization can result in loss of function or abnormal gene expression, which can lead to a diseased state. Thus, cell organization, mechanics, and electric signals must all be linked to produce a viable, functional tissue.

Focused efforts have tried to repair tissue by mimicking 3-D tissue architecture, extracellular matrix, and cell organization. For example, organ printing was established as a bottom-up approach that uses 100- to 500-µm aggregates of cells, known as tissue spheroids, as building blocks to make 3-D tissue constructs (Ruei-Zeng and Hwan-You, 2008). Robotic bioprinting of hydrogel droplets containing cells can be used to dispense or digitally spray tissue spheroids to achieve multicellular structures (Wang et al., 2006). Cells then self-assemble within and between spheroids to form larger, integrated structures. However, mass-transport limitations hinder the advancement of this technology.

In summary, the ability to enhance tissue performance is limited by (1) the need to obtain adequate and substantial numbers of viable cells, (2) mass-transport characteristics that dictate cell viability, and (3) the need to recapitulate the tissue architecture and cell organization that are required for tissue function. Tissue-engineering methods are focused on clinical repair, and current methods are unable to surpass the functioning of healthy tissue.

Worldwide Research

Tissue engineering has commercial applications in ligament repair and replacement, and epidermal constructs. The committee found that the countries with companies that provide products in this field include Australia, France, Italy, Germany, the United States, the United Kingdom, Switzerland, Japan, and Korea. Research on organ regeneration and bone replacement is also under way.

FATIGUE: JUDGMENT AND DECISION MAKING

Good human–machine system design exploits human strengths (such as pattern recognition and decision making) and protects against human weaknesses. “The human operator brings much more performance variability to a system than one finds in [reliable] software and modern hardware…. Once an operator has been trained and is current in system operation, the greatest

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2“Hematopoietic stem cells are immature cells that develop into all types of blood cells including white blood cells, red blood cells and platelets.” National Institutes of Health, U.S. Department of Health and Human Services. 2011. Stem Cell Information. Available at http://stemcells.nih.gov/info/glossary. Accessed July 31, 212. For more information on hematopoietic stem cells, see http://stemcells.nih.gov/info/basics/basics4.asp. Accessed July 31, 2012.

3Mesenchymal stem cells are “rare cells mainly found in the bone marrow that can give rise to a large number of tissue types such as bone, cartilage (the lining of joints), fat tissue and connective tissue (tissue that is in between organs and structures in the body).” Texas Heart Institute. 2009. Available at http://texasheart.org/Research/StemCellCenter/Glossary.cfm. Accessed July 31, 2012.



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