gms | German Medical Science

Objectives/Interrogation: Nitric oxide (NO) is a pivotal biological molecule in revascularization and nerve regeneration process after peripheral nerve injury. Recently, biomaterial advances introduce NO-releasing silica nanoparticle, which may offer the controlled and sustained delivery of NO to the targeted tissues. We hypothesized that NO-releasing nanoparticle promotes revascularization and functional recovery in rat sciatic nerve crushing model.

Methods: Forty-eight Lewis rats were divided in two groups of 24 rats each. A standardized crushed sciatic nerve of group I was treated with NO-releasing silica nanoparticle in fibrin glue carrier. The crushed sciatic nerve of group II was augmented in fibrin glue without NO nanoparticle. Four rats from each group were sacrificed and micro-angiography using a colored polymer dye was performed to evaluate the neural capillary density of sciatic nerve. We evaluated the sciatic functional index (SFI) using the walking tract test weekly. We measured maximum isometric tetanic force of tibialis anterior (TA) muscle and posterior calf muscle weight at 3 and 6 weeks after injury. All results of TA muscle force and muscle weight were normalized to the contralateral side. We also evaluated the histomorphometry of sciatic nerve.

Results and Conclusions: Microangiography showed that NO-releasing silica nanoparticle increased the neural capillary density of the crushing site of sciatic nerve 3 days after injury. Sciatic function index of animals treated NO-releasing silica nanoparticle was better than that of animals without NO on 4 weeks after injury. NO-releasing silica nanoparticle reduced muscle atrophy on 3 weeks after injury in terms of wet muscle weight. NO- nanoparticle enhanced the TA muscle force on 3 and 6 weeks after injury, but a significant effect was apparent with a mean intergroup difference on 6 weeks after injury. The number of myelinated axon and muscle weight of animals treated NO-nanoparticle was higher on 3 weeks after injury.

In conclusion, our results suggest that NO releasing silica nanoparticle enhance the revascularization of rat sciatic nerve in early phase after crushing injury, promote axonal regeneration and functional recovery in the early phase based on evidences from morphometric analysis and sciatic functional assessment. These findings provide a possible new avenue of using exogenous nitric oxide therapeutically.