Comparative evaluation of nerve repair and local tissue response following ReFeel^® nerve cuff implantation in a rat sciatic model

Peripheral nerve injuries (PNIs) pose a persistent clinical challenge, with current repair strategies limited by material biocompatibility, degradation, and regenerative efficacy. This study evaluates the in vivo performance of ReFeel®, a novel bioresorbable alginate-polyglycolic acid (PGA) nerve cuff, in two rat sciatic nerve models, compared to commercial collagen-based repair devices NeuroMatrix® (conduit) and NeuroMend® (wrap).

Two studies were conducted in Sprague-Dawley rats using either a 10 mm sciatic nerve gap model (ReFeel® vs. NeuroMatrix®) or a no-gap intact sciatic nerve perineural wrap model (nerve exposed but not transected), comparing ReFeel® with NeuroMend®. Functional, histological, immunohistochemical, and morphometric assessments were performed at 1 week, 8 weeks, and 26 weeks (gap model) and 1 week, 8 weeks, and 13 weeks (wrap model). Tissues were analyzed using hematoxylin and eosin (H&E), Masson's trichrome, Safranin-O, NF200, S-100, and toluidine blue staining. Degradation, host response, axon regeneration, Schwann cell activity, and fibrosis were quantified.

ReFeel® demonstrated superior Schwann cell alignment and axonal regeneration, particularly at 26 weeks, with near-complete scaffold resorption and minimal fibrotic encapsulation. Quantitative scores showed higher axon densities and comparable G-ratios versus NeuroMatrix®. In the wrap model, ReFeel® matched NeuroMend® in axon count and morphology at 13 weeks, with greater consistency in tissue remodeling. ReFeel® showed earlier material clearance, reduced chronic inflammation, and increased fatty infiltration, suggesting improved biocompatibility and scaffold integration.

ReFeel® supports robust peripheral nerve regeneration and degrades in synchrony with tissue remodeling. Compared to collagen-based devices, it enhances central and distal regeneration, promotes restoration of normal nerve homeostasis, and reduces fibrosis and chronic host response. Its ease of application further supports its potential as an effective scaffold for peripheral nerve repair. These findings validate the regenerative potential of alginate-PGA biomaterials and support the clinical translation of ReFeel® as a next-generation nerve repair solution, particularly for bridging nerve gaps or preventing perineural adhesions.