Utilizing biological responses to evaluate thein vivofate and biocompatibility of reduced graphene oxide-integrated nerve guidance conduits for peripheral nerve repair.

Reduced graphene oxide (rGO) has been widely incorporated into nerve guidance conduits (NGCs) to promote peripheral nerve regeneration owing to its physicochemical properties. However, some studies have reported potential biocompatibility risks of rGO and raised concerns about its possible adverse effects on nerve regeneration. In this study, anin vivochallenge model was established. Optical microscopy techniques were comprehensively employed to track the distribution and degradation behavior of rGO after implantation of rGO-incorporated NGCs, and biological evidence at both cellular and tissue levels was integrated to support the degradation-compatibility evaluation of rGO. Histological observations revealed the presence of rGO fragments and the formation of fibrous capsule walls. Immunofluorescence staining showed that rGO did not persistently interfere with the expression of nerve repair-related proteins up to 26 weeks post-implantation. RNA-sequencing confirmed inflammation at the implantation site within 4 weeks, as well as enrichment of differentially expressed genes in categories associated with nerve repair and cellular energy metabolism. These findings indicate that, within the framework of this model, the material exhibits biosafety during nerve repair and regeneration, although non-transient biocompatibility risks still warrant careful consideration. This study provides a theoretical support and experimental reference for improving the biocompatibility evaluation of graphene oxide derivatives.