Abstract
Tension-free surgical reconstruction of transected digital nerves in humans is regularly performed using autologous nerve grafts (ANGs) or bioartificial nerve grafts. Nerve grafts with increased bendability are needed to protect regenerating nerves in highly mobile extremity parts. We have recently demonstrated increased bendability and regeneration supporting properties of chitosan nerve guides with a corrugated outer wall (corrCNGs) in the common rat sciatic nerve model (model of low mobility). Here, we further modified the hollow corrCNGs into two-chambered nerve guides by inserting a perforated longitudinal chitosan-film (corrCNG[F]s) and comprehensively monitored functional recovery in the advanced rat median nerve model. In 16 adult female Lewis rats, we bilaterally reconstructed 10 mm median nerve gaps with either ANGs, standard chitosan nerve guides (CNGs), CNGs (CNG[F]s), or corrCNG[F]s (n = 8, per group). Over 16 weeks, functional recovery of each forelimb was separately surveyed using the grasping test (reflex-based motor task), the staircase test (skilled forelimb reaching task), and non-invasive electrophysiological recordings from the thenar muscles. Finally, regenerated tissue harvested from the distal part of the nerve grafts was paraffin-embedded and cross-sections were analyzed regarding the number of Neurofilament 200-immunopositive axons and the area of newly formed blood vessels. Nerve tissue harvested distal to the grafts was epon-embedded and semi-thin cross-sections underwent morphometrical analyses (e.g., number of myelinated axons, axon and fiber diameters, and myelin thicknesses). Functional recovery was fastest and most complete in the ANG group (100% recovery rate regarding all parameters), but corrCNG[F]s accelerated the recovery of all functions evaluated in comparison to the other nerve guides investigated. Furthermore, corrCNG[F]s supported recovery of reflex-based grasping (87.5%) and skilled forelimb reaching (100%) to eventually significantly higher rates than the other nerve guides (grasping test: CNGs: 75%, CNG[F]s: 62.5%; staircase test: CNGs: 66.7%, CNG[F]s: 83.3%). Histological and nerve morphometrical evaluations, in accordance to the functional results, demonstrated best outcome in the ANG group and highest myelin thicknesses in the corrCNG[F] group compared to the CNG and CNG[F] groups. We thus clearly demonstrate that corrCNG[F]s represent promising innovative nerve grafts for nerve repair in mobile body parts such as digits.
Highlights
Traumatic injuries of peripheral nerves represent a frequent reason for morbidity and life-long physical restrictions
While implantation of ANGs still showed fast and most complete functional recovery, we clearly demonstrate that corrugated chitosan nerve guide (corrCNG)[F]s accelerated and for some skilledforelimb reaching significantly increased the recovery of all functions evaluated in comparison to the other bioartificial nerve guides investigated
It needs to be stressed again that in this study 10 mm median nerve gaps were bilaterally reconstructed in 16 female Lewis rats and that the numbers given for specimen analyzed per group refer to median nerves repaired with the respective approach (n = 8 for each group) instead of the number of animals studied
Summary
Traumatic injuries of peripheral nerves represent a frequent reason for morbidity and life-long physical restrictions. About 2.8% of all trauma patients suffer from peripheral nerve injuries (Noble et al, 1998). In many cases, these injuries lead to life-long dependency on aid and substantial reduction of quality of life (Noble et al, 1998). Recovery of peripheral nerve injuries often remains incomplete and progresses slowly. Peripheral nerve injuries most often affect the upper limbs (Kouyoumdjian, 2006; Deumens et al, 2010) and in 6.4% of all hand injuries, the joint-crossing digital nerves are affected (Renner et al, 2004)
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