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Repair of a Segmental Peripheral Nerve Injury with an Aligned-Nanofiber Conduit Filled with a Collagen and Hyaluronan Hydrogel in a Rat Model
Sonja Limburg, MD1; Sunil Kumar Joshi, BA1; Rebeccah Landmann, MS1; Jenny Jin, MD1; Qia Zhang, BA1; Hubert Kim, MD, PhD2; Alfred Kuo, MD, PhD1; (1)San Francisco VA Medical Center, (2)University of California
San Francisco VA Medical Center, San Francisco, 94121, CA, USA

No current treatment reliably restores function after segmental peripheral nerve injuries. The gold standard, nerve autograft, is limited by availability and donor site morbidity. Longitudinally aligned-nanofiber conduits are a promising alternative to autograft, and enhance nerve regeneration compared to non-aligned conduits in animal models. We hypothesized that biological cues provided by delivery of a collagen and hyaluronan hydrogel and nerve growth factor (NGF) within a tubular, aligned-nanofibrous conduit will further stimulate nerve regeneration over conduit alone. The purpose of this study was to assess motor and sensory recovery after repair of a segmental sciatic nerve defect in a rat model using an aligned poly-L-lactide-co-caprolactone (PLCL) conduit filled with hydrogel and NGF.

Ten millimeter segments of the right sciatic nerve were resected in female Lewis rats (n = 9/group) and repaired with reversed sciatic nerve autograft, PLCL, PLCL/Hydrogel, and PLCL/Hydrogel/NGF. Sensory recovery was assessed at three weeks and twelve weeks using a withdrawal assay from thermal stimulation. At twelve weeks, bilateral gastrocnemius tetanic force, muscle weight, nerve conduction, and compound muscle action potential (CMAP) were measured.

After 12 weeks, there was no significant difference in gastrocnemius tetanic force among the groups, with a trend towards larger force generation with autograft repair (p=0.09). Autograft also had the greatest recovery of gastrocnemius muscle mass (*p<0.0001). The amplitude of the gastrocnemius CMAP was higher with autograft compared to the three conduit groups (**p=0.0018). For nerve conduction latency, all four treatment groups were slower than normal nerve, which served as a control (*p<0.05) but there was no difference among the four groups (p=0.5983). At three weeks, the withdrawal from thermal stimulus was significantly slower in the operated limb compared to contralateral limb in all groups (p<0.0208) (See Figure). At 12 weeks, the two hydrogel groups had statistically equivalent withdrawal times in both limbs (p>0.3133), while the autograft and empty PLCL groups still withdrew slower than control limbs (p<0.021).

Our optimized PLCL conduit provides a promising alternative to nerve autograft. In this study, we demonstrated enhanced sensory recovery, but no improvement of motor recovery. Ultimately, we hope to design a conduit that can successfully replace autograft repair, avoiding the morbidity of donor nerve harvest while producing equivalent or better results than autograft for both, sensory and motor function.


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