Neuroma Prevention with a Novel In Situ Forming Hydrogel in a Rat Sciatic Nerve Model

Background: Symptomatic neuromas are a common source of chronic pain after transection injury to peripheral nerves. This study evaluated a novel, bioresorbable in situ forming hydrogel nerve cap (allay Nerve Cap, Tulavi Therapeutics) for its ability to reduce the risk of neuroma formation in a rat model of sciatic nerve transection neurectomy. Methods: Sprague-Dawley rats (n = 54) underwent surgical transection of the left sciatic nerve, followed by placement of the hydrogel nerve cap (n = 18), a conventional nerve cap (n = 18), or a sham procedure (n = 18) with no cap. Animals were evaluated weekly for recovery of sensorimotor function (Hargreaves test) and euthanized at 4 weeks and 3 months for gross and histopathologic evaluation. Results: At 4-week and 3-month necropsy, no animals in the hydrogel cap group (0 of 14), 3 of 9 animals in the conventional cap, and 6 of 10 animals in the sham group had developed neuromas. Animals in the hydrogel cap group demonstrated faster return to baseline sensitivity than other groups. Histologically, the hydrogel prevented leukocyte infiltration to the nerves. The observed inflammatory response to the hydrogel cap was consistent with that expected of a resorbable implant. Histological neuroma scores were lower for the hydrogel cap versus conventional cap ( P = 0.0157) and sham ( P = 0.0007). Conclusions: The in situ forming hydrogel-based nerve cap prevented neuroma formation in a rat model of peripheral nerve transection over a clinically relevant timeframe. Although translational study in humans is needed, these results suggest that the hydrogel cap may be capable of preventing neuroma formation following peripheral nerve injury.