Sutureless nerve repair has been regarded as a promising technique for nerve repair as the suture materials often results in neuroma formation and scar tissue that impede nerve regeneration. The aim of this study was to analyze the mechanical stability and morphological outcome of sutureless repair using fibrin glue conduit and an alternative approach of modified suture placement. Using rat sciatic nerve, we tested the following experimental conditions: conventional suture repair; single suture combined with fibrin glue repair, and fibrin conduit reinforced with modified suture or fibrin glue. Nerve detachment anatomical measures such as axon density, myelin, and fiber caliber were analyzed for evaluation of nerve regeneration. Muscle atrophy were evaluated by muscle wet weight and H&E staining. All animals in sutureless repair group exhibited complete detachment or elongation by two or four weeks after repair. No detachment was found in any other groups. Animals treated with fibrin conduit reinforced with modified suture showed better axonal regeneration with good alignment. There were no significant differences in axon caliber among the groups. Muscle atrophy was found in all groups and there was no significant difference in muscle wet-weight among the groups. In summary, sutureless nerve repair with fibrin glue was mechanically unstable for resistance of mechanical stretches, fibrin glue conduit with modified suture placement is mechanically stable and resulted in better morphological outcome.

Animals treated with CR and epineural stem cell injection showed enhanced anatomical and functional recovery. Muscle Nerve 58: 566-572, 2018.

Peripheral nerve injuries often result in lifelong disabilities despite advanced surgical interventions, indicating the urgent clinical need for effective therapies. In order to improve the potency of adipose-derived stem cells (ASC) for nerve regeneration, the present study focused primarily on ex-vivo stimulation of ASC by using growth factors, i.e., nerve growth factor (NGF) or vascular endothelial growth factor (VEGF) and secondly on fibrin-hydrogel nerve conduits (FNC) assisted ASC delivery strategies, i.e., intramural vs. intraluminal loading. ASC were stimulated by NGF or VEGF for 3 days and the resulting secretome was subsequently evaluated in an in vitro axonal outgrowth assay. For the animal study, a 10 mm sciatic nerve gap-injury was created in rats and reconstructed using FNC loaded with ASC. Secretome derived from NGF-stimulated ASC promoted significant axonal outgrowth from the DRG-explants in comparison to all other conditions. Thus, NGF-stimulated ASC were further investigated in animals and found to enhance early nerve regeneration as evidenced by the increased number of β-Tubulin III+ axons. Notably, FNC assisted intramural delivery enabled the improvement of ASC’s therapeutic efficacy in comparison to the intraluminal delivery system. Thus, ex-vivo stimulation of ASC by NGF and FNC assisted intramural delivery may offer new options for developing effective therapies.

We demonstrate the potential of the micro computed tomography for non-destructive monitoring of peripheral nerves inside the conduits.