This research will enable the development of comprehensive criteria to evaluate the efficacy and safety of a new generation of neural implants. In the development of such criteria, they will develop fundamental insight into the relationship between nerve biomechanics, morphology, and electrophysiological function. Several aspects of our project are transformative. They have developed a rigorous quantitative approach to directly examine in vivo nerve structure-function relationships. This will bridge numerous gaps in the literature regarding influences of nerve architecture on function. They will also use kinematic analysis to calibrate our measurements of nerve deformation to a baseline physiological frame of reference, allowing one to scale and compare relative nerve deformation across species or in different experimental configurations.
This approach represents a logical and necessary shift from arbitrary or non-normalized nerve strains and strain rates reported in previous studies of peripheral nerve plasticity. Several elements of the experimental design are innovative, including the integration of nerve electrode implantation with in vivo biomechanical and electrophysiological measurement, and the use of cellular elements such as Bands of Fontana to assess regional nerve deformation.
Devices of increasing functionality, complexity, and innovation have been designed to interface with the peripheral nervous system, to restore motor and sensory functional losses resulting from a wide range of neuromuscular disorders or injury. Through our NSF-funded research, in collaboration with scientists at the USFDA, our team of undergraduates, graduate students, postdoctoral scholars, and principal investigators examined the possibility that implantation of peripheral nerve devices can change the mechanical environment of a nerve, and as a consequence, also disrupt nerve function. This study was motivated by the fact that an appropriate mechanical environment typically enables a nerve to function properly during movement of joints spanned by that nerve. Disruption of this environment can result in inefficient conduction of electrical signals by the nervous system, in a manner analogous to conduction deficits in entrapment neuropathies such as carpal tunnel syndrome. To test this hypothesis, we developed a new experimental platform to simultaneously measure the deformation (stretch) in a rat sciatic nerve and its ability to conduct electrical signals. We validated this system by comparing nerve deformation and action potential propagation during knee and ankle movement in uncuffed nerves (control) with those connected to a cylindrical cuff electrode. Such electrodes are similar to those used for a variety of clinical applications, ranging from phrenic nerve stimulation to functional stimulation to restore movement following spinal cord injury. We also performed preliminary Micro-CT imaging of peripheral nerves (Figure), as an initial approach to assess nerve deformation after implantation without need for additional surgery. Our results indicated that while nerves were still able to conduct action potentials in the presence of a cuff electrode, there was significantly more variability in this conduction. This inefficiency strongly correlated with observed differences in the regional deformation of the nerve, suggesting that an appropriate mechanical environment indeed influences nerve electrical function. Micro-CT results indicated that rat sciatic nerves distribute their deformation regionally when stretched, with the points at which the sciatic nerve trunk splits into tibial, peroneal, and sural branches playing a major influence on this distribution. Based on our findings, we propose that the mechanical environment of a nerve should be factored into the design of new nerve-interfacing devices, as well as their implantation. Such consideration has strong implications for successful device development and post-implantation performance, towards improved restoration of motor and sensory function. Disclaimer: The content of this report does not reflect the opinions of the U.S. Food and Drug Administration.
