Introduction: Strategies for improving nerve regeneration through nerve gaps include the development of new biological and synthetic materials, such as poly (3, 4-ethylenedioxythiophene) or PEDOT, which is an electrically conducting polymer. PEDOT functions similar to a wire; it increases electrical signals within the nerve in order to compensate for the lack of nerves.

Materials &Methods: We constructed a grafting material to augment regenerated nerve conduction. We incorporated PEDOT, as the lining of an agarose-based hydrogel tube. We tested the following concepts: 1) nerve fibers regenerate through a nerve graft containing PEDOT, and 2) successfully reinnervate target skeletal muscles. We tested four synthetic materials as peripheral nerve conduits; two of which included PEDOT. The recovery of these two grafts was compared with a control nerve autograft. The groups compared were: nerve autograft (AUTO), polydimethylsiloxane (PDMS), plain agarose (AG-P/Hydrogel), agarose with a spiral layer of PEDOT lining (S-OT), and agarose completely lined with PEDOT (F-DOT). Rat peroneal nerve was lesioned and repaired with a 12 mm long interpositional graft or conduit (n=5 per group). Following a 90 day recovery period, muscle force properties were measured by stimulating the peroneal nerve proximal to the repair. Nerve histology was performed. Data was collected with bright-light microscopy and with integrated morphometry analysis software.

Results & Conclusion: Review of mid-graft histology (Figure 1) indicates there are regenerating nerve fibers in all the grafts. When ranked on nerve fiber density (nerve count/total area), the group order is AUTO>PDMS>S-DOT = F-DOT>>AG-P. Nerve fibers grew beside the agarose and the PEDOT but not through it. Muscle contractile forces indicate muscle fibers were successfully reinnervated in all groups except the AG-P/ Hydrogel group (Table 1). Nerve fibers regenerate through a nerve graft containing PEDOT and successfully reinnervate target skeletal muscles. Based on the latter half of Table 1, quantitative analysis confirms that nerve fiber density ranks in the order mentioned above. Measurements taken were % Neural Area, which calculates the percentage of nerves over the whole region. % Neural Debris calculates the percentage of debris over the entire region.  % Collagen is the amount of collagen in the region. Axon: Fiber Ratio is calculated as the total area of the axoplasm: total area of the nerve. After analysis of these measurements, it can be concluded that PEDOT is the best synthetic material out of the four grafts in terms of muscle force and the aforementioned measurements.

The views expressed in this work are those of the authors and do not necessarily reflect official Army policy. This work was supported by the Department of Defense Multidisciplinary University Research Initiative (MURI) program administered by the Army Research Office under grant W911NF0610218.

Table 1. Summary of Statistical Test Data by Graft Material
	Graft Material
	AUTO (Control)	PDMS	AG-P (Hydrogel)	S-DOT	F-DOT
Sample size	4	5	5	5	5
EDL muscle force (mN)	2118±988	628±743*	7±11*	243±536*	125±174*
TA muscle force (mN)	5453±3555	1095±1558*	3.0±3.2*	521±1107*	564±1023*
EDL muscle mass (mg)	108±30.3	67.0±27	50.0±7.5*	60±16*	54±6.4*
TA muscle mass (mg)	385±168	203±86*	144±17*	178±52*	189±29*
Nerve Count	176	38	0	2	4
Nerve Fiber Density	7.96x10-3	1.65 x10-3	0	8.64x10-5	1.73 x 10-4
% Neural Area	54.80 %	1.72%	0 %	0.11%	0.16%
% Neural Debris	2.69 %	7.37%	37.94%	17.18%	11.54%
% Collagen	42.51%	90.90%	62.06 %	82.71%	88.30%
Axoplasm: Nerve Fiber Ratio	0.30	0.33	N/A	0.17	0.22
Values are group mean±SD. * Indicates statistically different from AUTO group, p<0.05. AUTO = autograft; PDMS = silicone graft; AG-P = agarose alone graft; S-DOT = agarose with a spiral layer of PEDOT, and F-DOT = agarose completely lined with PEDOT. EDL=extensor digitorum longus muscle; TA = Tibialis Longus muscle.