Collagen epineurial substitute-assisted neurorrhaphy is superior to conventional end-to-end neurorrhaphy in a rat model of peripheral nerve injury.

Background: Peripheral nerve injuries (PNIs) are common and may result in profound and persistent functional deficits. Although end-to-end neurorrhaphy remains the gold standard for nerve repair, clinical outcomes are frequently suboptimal. This study aimed to validate a novel surgical method using a collagen epineurial substitute (CES) to minimize the number of sutures and reduce nerve tension at the coaptation site. Methods: Finite element analysis (FEA) was performed to simulate stress distribution and guide suture configuration. Sprague-Dawley (SD) rats underwent sciatic nerve transection and were allocated into six groups: control; end-to-end neurorrhaphy using 1, 3, or 6 epineurial sutures; or epineurial substitute-assisted repair with one or no coaptation-site sutures. Mechanical stability was validated by tensile testing, while the Sciatic Functional Index (SFI) and gastrocnemius muscle weight were used as screening assessments to evaluate functional recovery. Histological outcomes, including vascularization and cellular alignment at the transection site, were also assessed. A further comparison between two representative groups, based on the equivalent mechanical stability was performed using behavioural tests for sensory recovery and electrophysiological testing for motor recovery to precisely track functional outcomes, together with Osmium staining for myelin and Silver staining for nerve fibres, to further investigate nerve tissue regeneration associated with microenvironmental changes. Results: To test if CES-assisted repair can stabilize the mechanical strength and reduce nerve tension at the coaptation site, we first used FEA and demonstrated that, under physiological tension (2%), CES-assisted nerve coaptation redistributed mechanical stress along the covering of nerve segment. In contrast, conventional neurorrhaphy showed the concentrated tension of nerve at the coaptation. These computational findings were further supported by biomechanical testing in the rat model. The failure load of constructs repaired with three coaptation-site sutures was not significantly different from that of epineurial substitute-assisted constructs without coaptation-site sutures (p = 0.0635) and was significantly lower than that of CES-assisted constructs incorporating a single coaptation-site suture (p = 0.0022). This optimised mechanical environment offered by CES-assisted neurorrhaphy led to a 63-82% increase in parallel direction ratios relative to suture-only repairs, thereby promoting superior cellular alignment at the nerve transection site, enhancing epineurial and intraneural vascularization and reducing suture-related inflammation. In contrast, excessive suturing impaired early regenerative responses, whereas the epineurial substitute approach facilitated a tension-free microenvironment conducive to axonal regeneration and tissue integration. Repair of transected nerves with epineurial substitute demonstrated accelerated sensory functional recovery, reflected by improved SFI, earlier responses to thermal and mechanical stimuli, significantly higher maximum evoked compound muscle action potential (CMAP) of the gastrocnemius muscle (P = 0.0034), preservation of distal nerve calibre, and improved fascicular organization compared with suture-only repairs. Conclusion: Repair of transected nerves using an epineurial substitute can mechanically stabilize the coaptation site and reduce the nerve tension compared with conventional end-to-end neurorrhaphy, thereby preserving alignment of fascicular architecture, promoting early pro-regenerative vascularization, minimizing suture-related trauma and enhancing functional recovery. The translational potential of this article: The integration of computational modelling and biomechanical validation in this study reveals a new way of repairing nerve using CES-assisted neurorrhaphy with less suture. The approach transfer point-load fixation in the end-to-end neurorrhaphy to distributed-load stabilization with less nerve tension at the coaptation site. While the study showed a translational potential for changing current clinical practice in peripheral nerve repair, further validation in large animal models and clinically relevant settings are required before application in routine surgical practice.