Perspectives on the role of bioengineering in neurotrauma research.

We are very pleased to have served as guest editors for this special issue on Bioengineering in Neurotrauma Research. This assembly of articles was particularly challenging, as we tried to capture cutting-edge research across an extremely diverse and broad engineering discipline. According to the online Merriam-Webster dictionary, bioengineering is the ‘‘biological or medical application of engineering principles or engineering equipment, also called biomedical engineering. ’’ The topics of the articles in this issue range from novel studies of axon stretching and guided regeneration, to computer modeling and new image processing techniques. In introducing this issue, we thought it would be of interest to put current research accomplishments in the context of history, as well as to anticipate future innovations. Although evidence of engineering influences in treating neurotrauma can be found as early as Neolithic times in the surgical practice of trephination to relieve symptoms of head injury (Levin et al., 1982; Granacher, 2007), the Renaissance period brought Galileo’s mathematics and measurement devices to physicians, launching the beginning of medical engineering. The first use of the term bioengineering was not until c. 1955, however, when there was a growing need for better medical instrumentation, surgical advancements, replacement organs, and life support in space. This was also the era that witnessed the beginning of tissue culture (Gey et al., 1952), and the pioneering human tolerance experiments of Colonel Stapp (Stapp, 1948; Stapp and Gell, 1951). Intracranial pressure monitoring began during the 1950s as well, initiating modern neurocritical care (Marion 1999; Marshall, 2000). Today, bioengineering in neurotrauma research encompasses areas from biosensing to intraoperative magnetic resonance imaging (MRI). Engineering applications to neurotrauma research can be seen in the use of cell and tissue preparations. Transection has been a model of injury since Galen accidently cut laryngeal nerves of a pig and Ramon y Cajal systematically cut axons (Ramon y Cajal, 1928). Biomechanics began to influence the field of cellular neurotrauma research in the 1990s (Ellis et al., 1995, Lucas and Wolf, 1991; Shepard et al., 1991), and over the next two decades, in vitro models became more sophisticated (Morrison et al., 1998; Kumaria and Tolias, 2008; Chen et al., 2009). In the present issue, Maguo and associates present a novel axonal injury system, addressing the need for even more high-throughput systems than most current systems can provide. Cullen and colleagues show the differences between loading mode of 3-D cultures, underlying the need to define input biomechanics. Elkin and co-workers use in vitro brain samples to study edema, lending mechanistic insight into the complex phenomenon of brain swelling, a basic yet critical physiological response to neural trauma. In addition to the study of cellular biomechanics and the acute injury response, cultures can be used to investigate regeneration of the damaged nervous system. The last three articles in this issue demonstrate different approaches to understanding growth cues and exploiting axogenesis for regenerative therapies. Voyiadjis and associates examine neurite outgrowth using novel microengineered channels and compare neurite preference to simulations based on predictive modeling. From the same group, Sundarataghavan and colleagues use microfluidics to guide neurites through 3-D collagen cultures, representing in vivo-like architecture. Loverde and co-workers present an innovative mechanical axon growth environment to slowly stretch axons and image growth and retraction in real time, providing a means to better understand tensioninduced growth of axons. The application of mechanics and finite element modeling to neural trauma has its roots in cadaver testing, from which the Wayne State Tolerance Curve was derived (see McLean and Anderson, 1997 for an account of the evolution of the biomechanics of traumatic brain injury [TBI] in the 20th century). In parallel, Denny-Brown and Russell proposed that a change in velocity would be required to cause brain damage (Denny-Brown and Russell, 1941). These and other studies led to the development of initial tolerance criteria, such as the Head Injury Criterion (HIC). Computer simulation capability has become much more advanced over the last two decades, and there is a need to use more accurate material properties for both human and animal studies. To this end, in the current issue Elkin and associates have measured the viscoelastic regional properties of juvenile and adult rat brain. Finite element models can also be used to better understand the