Hyaluronate-Alginate Gel-Coated Porcine Small Intestine Submucosa for Nerve Protection Minimizes Extraneural Collagen Deposition in a Preclinical Model.

Purpose: This study evaluated the use of a hyaluronate-alginate gel-coated small intestine submucosa (HA-SIS) to protect a nontransected nerve in an adhesion rodent model. Methods: The sciatic nerve of 60 male Lewis rats underwent neurolysis, with subsequent surgical treatments varying according to their assigned groups. The sham group (n = 20) was surgically closed immediately after neurolysis. The muscle bed of the untreated group (n = 20) was traumatized with a bipolar coagulator and then surgically closed. The muscle bed of the HA-SIS group (n = 20) was traumatized with a bipolar coagulator, the nerve was wrapped with HA-SIS, and the site was surgically closed. Ten animals in each group were terminated at each timepoint, 6 and 26 weeks. Surgical sites were assessed by gross pathology and histology. Results: Gastrocnemius muscle wet weight was significantly higher in the HA-SIS group than in the untreated and sham groups at 26 weeks. At both timepoints, adhesion scores were highest in the untreated group. At both timepoints, extraneural collagen deposition was significantly higher in the untreated group than in the sham and the HA-SIS groups. At 26 weeks, CD68-positive macrophages were significantly higher in the untreated group than in the HA-SIS group. No significant differences were noted across groups for intraneural collagen-to-cell ratio and blood vessel count. Conclusions: These results demonstrate that nerve wrapping with HA-SIS in an injured muscle bed reduces external nerve adhesions, extraneural collagen deposition, and long-term inflammation (CD68-positive macrophages) compared with the results of unwrapped nerves. Clinical relevance: This level five study examines the impact of a hostile environment on nerve health, as well as the influence of a nerve protection device on diminishing its detrimental effects.