Functional Regeneration of Defected Peripheral Nerve using Conduit Electrode with Electrical Stimulation Taehyung Lee1*, Hui Pan2 In Sook Kim2 Soon Jung Hwang2,3, Sung June Kim1 1
2
School of Electrical Engineering and Computer Science, Seoul National University, Department of Oral & Maxillofacial Surgery, School of Dentistry, Seoul National University, 3 Dental Research Institute, Seoul National University, Seoul, Korea *
[email protected]
INTRODUCTION Peripheral nerve defect can regenerate over long distance by suture repair techniques [1]. Recently, many research groups have studied the regeneration of nerve functionality by electrical stimulation. In this paper, we present a new electrical stimulation device for regeneration of defected nerve. We report that functional regeneration of defected peripheral nerve using the conduit electrode with electrical stimulation. MATERIALS AND METHODS The electrode was fabricated by a polymer-based process. The polyimide was used as a flexible substrate. The fabricated polyimide based electrode was rolled and cured for shaping. Then a collagen solution was coated into surface of electrode for improving adhesion of nerve cells. A stimulator IC was designed using a CMOS fabrication process. The IC was designed to generate a biphasic electrical current for electrical stimulation on the nerve. The stimulator IC was packaged using a biocompatible polymer with a battery. We used a biphasic current pulse with 20 µA of amplitude and 100 Hz of pulse rate. Eighteen adult rats were used in this study. A 7-mm gap was made in rat sciatic nerve by suturing the stumps into a conduit electrode. A control group of rats (n = 8) received no stimulation while an experimental group I (n = 8) and II (n = 4) received continuous stimulation for four weeks and for two weeks and was in the convalescent stage for another two weeks, respectively. After four weeks, all animals were anesthetized and received surgery to expose the sciatic nerve. Functional recovery was characterized by walking behavior test measured by footprint analysis and evoked nerve action potential. RESULTS Every two weeks a walking behavior tests were performed; a sciatic functional index (SFI) and a static sciatic index (SSI). The results of SFI and SSI were measured as Table 1. The defected nerves from the experimental groups of rats were regenerated. There was a clear different in the neural activity in the two groups. When stimulated by a stimulus impulse, the evoked action potentials were clearly shown in the experiment groups while none appeared in the control group. The stimulus threshold had a difference between in the experimental groups. The stimulation threshold for the evoked potential was observed as shown in Table 2. Figure 1 show the evoked action potential recorded from normal (a), control (b) and experimental groups (c).
Table 1: SFI and SSI at four weeks after implantation Behavior test Group (n) Static Sciatic Index Sciatic Functional Index (SFI) (SSI) -95.05 ± 2.537 -109.02 ± 1.384 Control Group (n=8) -90.86 ± 2.587 -95.68 ± 1.772 Experimental Group I (n=4) -90.55 ± 0.993 -92.73 ± 1.683 Experimental Group II (n=8)
Table 2: Recorded nerve action potential at four weeks after implantation Evoked nerve action potential Group (n) Positive/Total (n/n) Threshold (mA) 20/20 0.22 ± 0.11 Normal Group (n=20) 0/8 No response Control Group (n=8) 3/4 1.60 ± 0.40 Experiment Group I (n=4) 7/8 1.69 ± 0.81 Experimental Group II (n=8)
(a)
(b)
(c)
Figure 1: Evoked nerve action potential
CONCLUSIONS The stimulation system for functional regeneration of peripheral nerve consisted of conduit type flexible electrode and implantable electronics designed for one time use. The nerves were continuously stimulated for two and four weeks and two tests were performed to evaluate the functional nerve regeneration. Neural responses were only observed in animals which received electrical stimulation. The effects of electrical stimulation on regeneration between 2 and 4 weeks are similar in this study.
REFERENCES [1] Fu SY, Gordon T, The cellular and molecular basis of pheripheral nerve regeneration, Mol Neurobiol. vol (14): 67-116, 1997 [2] A. A. Al–Majed, C. M. Neumann, T. M. Brushart, and T. Gordon, Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration, The Journal of Neuroscience, vol (20): 2602–2608, 2000 [3] T. M. Brushart, R. Jari, V. Verge, C. Rohde, and T. Gordon, Electrical stimulation restores the specificity of sensory axon regeneration, Experimental Neurology, vol (194): 221–229, 2005
