The purpose of this paper is to present results from methodologies used in our laboratory that are targeted toward identifying specific brain injury thresholds. Results from studying one form of brain injury, diffuse axonal injury, are presented in this report. Physical models, or surrogates, of the skull–brain complex are used to estimate the relationship between inertial loading and brain deformation. A porcine model of diffuse axonal injury, developed with information from these physical models and earlier in vitro tissue modeling studies, is used to correlate histologic and radiologic evidence of axonal injury to predicted regions of injury from the experimental and theoretical analysis. These results form the basis for developing improved diffuse brain injury tolerance levels, as well as identifying new means of diagnostic and treatment techniques for diffuse axonal injury. Key words: diffuse axonal injury; physical models; animal models; diffuse brain injury tolerance levels

The dura mater is the outermost and most substantial meningial layer of central nervous system (CNS) tissue that acts as a protective membrane for the brain and spinal cord. In animal models of traumatic brain injury and spinal cord injury, mechanical insults are often delivered directly to the dura to injure the underlying tissue. As such, including a description of the mechanical properties of dura mater is critical for biomechanical analyses of these models. We have characterized the mechanical response of dura mater from the rat brain and spinal cord in uniaxial tension. Testing was performed at low (0.0014 sec ⁻¹ ) and high (19.42 sec ⁻¹ ) strain rates. Both rat cranial dura and spinal dura demonstrated non-linear stress-strain responses characteristic of collagenous soft tissues. The non-linear increase in stress lagged in the spinal dura compared to the cranial dura. The slow rate data was fit to a one-term Ogden hyperelastic constitutive law, and significant differences were observed for the stiffness, G , and the parameter, α, which nominally introduces non-linearity. High strain rate stress-relaxation tests were performed to 10% strain, which was held for 10 sec. The relaxation was fit to a four-term Prony series exponential decay. Cranial dura and spinal dura demonstrated similar overall relaxation, but significant differences were identified in the distribution of the relaxation over the Prony series parameters, which demonstrated that cranial dura tended to relax faster. Polarized light microscopy revealed that the structural entities of spinal dura were aligned in the axial direction, whereas cranial dura did not demonstrate a preferential alignment. This was confirmed qualitatively with Masson's Tri-chrome and Verhoeff's Van Gieson staining for collagen and elastin, which also indicated greater elastin content for the spinal dura than for the cranial dura.

Type-I collagen is an attractive scaffold material for tissue engineering due to its ability to self-assemble into a fibrillar hydrogel, its innate support of tissue cells through bioactive adhesion sites, and its biodegradability. However, a lack of control of material properties has hampered its utility as a scaffold. We have modified collagen via the addition of methacrylate groups to create collagen methacrylamide (CMA) using a synthesis reaction that allows retention of fundamental characteristics of native collagen, including spontaneous fibrillar self-assembly and enzymatic biodegradability. This method allows for a rapid, five-fold increase in storage modulus upon irradiation with 365 nm light. Fibrillar diameter of CMA was not significantly different from native collagen. Collagenolytic degradability of uncrosslinked CMA was minimally reduced, while photocrosslinked CMA was significantly more resistant to degradation. Live/Dead staining demonstrated that a large majority (71%) of encapsulated mesenchymal stem cells remained viable 24 h after photocrosslinking, which further increased to 81% after 72 h. This material represents a novel platform for creating mechanically heterogeneous environments.