Peripheral nerves are highly susceptible to injuries induced from everyday activities such as falling or work and sport accidents as well as more severe incidents such as car and motorcycle accidents. Many efforts have been made to improve nerve regeneration, but a satisfactory outcome is still unachieved, highlighting the need for easy to apply supportive strategies for stimulating nerve growth and functional recovery. Recent focus has been made on the effect of the consumed diet and its relation to healthy and well-functioning body systems. Normally, a balanced, healthy daily diet should provide our body with all the needed nutritional elements for maintaining correct function. The health of the central and peripheral nervous system is largely dependent on balanced nutrients supply. While already addressed in many reviews with different focus, we comprehensively review here the possible role of different nutrients in maintaining a healthy peripheral nervous system and their possible role in supporting the process of peripheral nerve regeneration. In fact, many dietary supplements have already demonstrated an important role in peripheral nerve development and regeneration; thus, a tailored dietary plan supplied to a patient following nerve injury could play a non-negotiable role in accelerating and promoting the process of nerve regeneration.

Peripheral nerve injury remains a clinical challenge with severe physiological and functional consequences. Despite the existence of multiple possible therapeutic approaches, until now, there is no consensus regarding the advantages of each option or the best methodology in promoting nerve regeneration. Regenerative medicine is a promise to overcome this medical limitation, and in this work, chitosan nerve guide conduits and olfactory mucosa mesenchymal stem/stromal cells were applied in different therapeutic combinations to promote regeneration in sciatic nerves after neurotmesis injury. Over 20 weeks, the intervened animals were subjected to a regular functional assessment (determination of motor performance, nociception, and sciatic indexes), and after this period, they were evaluated kinematically and the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed confirming the beneficial effects of using these therapeutic approaches. The use of chitosan NGCs and cells resulted in better motor performance, better sciatic indexes, and lower gait dysfunction after 20 weeks. The use of only NGGs demonstrated better nociceptive recoveries. The stereological evaluation of the sciatic nerve revealed identical values in the different parameters for all therapeutic groups. In the muscle histomorphometric evaluation, the groups treated with NGCs and cells showed results close to those of the group that received traditional sutures, the one with the best final values. The therapeutic combinations studied show promising outcomes and should be the target of new future works to overcome some irregularities found in the results and establish the combination of nerve guidance conduits and olfactory mucosa mesenchymal stem/stromal cells as viable options in the treatment of peripheral nerves after injury.

The repair of severe nerve injuries requires an autograft or conduit to bridge the gap and avoid axon dispersion. Several conduits are used routinely, but their effectiveness is comparable to that of an autograft only for short gaps. Understanding nerve regeneration within short conduits could help improve their efficacy for longer gaps. Since Schwann cells are known to migrate on endothelial cells to colonize the “nerve bridge”, the new tissue spontaneously forming to connect the injured nerve stumps, here we aimed to investigate whether this migratory mechanism drives Schwann cells to also proceed within the nerve conduits used to repair large nerve gaps. Injured median nerves of adult female rats were repaired with 10 mm chitosan conduits and the regenerated nerves within conduits were analyzed at different time points using confocal imaging of sequential thick sections. Our data showed that the endothelial cells formed a dense capillary network used by Schwann cells to migrate from the two nerve stumps into the conduit. We concluded that angiogenesis played a key role in the nerve conduits, not only by supporting cell survival but also by providing a pathway for the migration of newly formed Schwann cells.

Thousands of people worldwide suffer from peripheral nerve injuries and must deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee adequate outcomes, and the development of new and compelling therapeutic options require the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. The anatomy of the common peroneal nerve and topographically related nerves, the functional consequences of its injury and a neurological examination directed at this nerve have been described. Furthermore, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options were described. Finally, a preliminary morphological and stereological study was carried out to establish control values for the healthy common peroneal nerves regarding this animal model and to identify preliminary differences between therapeutic methods. This study allowed to define the described lateral incision as the best to access the common peroneal nerve, besides establishing 12 and 24 weeks as the minimum periods to study lesions of axonotmesis and neurotmesis, respectively, in this specie. The post-mortem evaluation of the harvested nerves allowed to register stereological values for healthy common peroneal nerves to be used as controls in future studies, and to establish preliminary values associated with the therapeutic performance of the different applied options, although limited by a small sample size, thus requiring further validation studies. Finally, this study demonstrated that the sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in humans and veterinary patients.

Before clinical approval of chitosan nerve conduits (CNCs) less than 10 years ago, substantial material degradation was not reported from pre-clinical research. The current study investigated the biodegradation of two different CNC variants in the median nerve model. In adult rats, 10 mm long CNCs were secured covering end-to-end repair sites. After 2, 6, 12, and 18 months, the implantation sites were inspected, and samples harvested. Histology was performed in order to analyze local immune response or foreign body tissue reaction around the devices or within nerve samples. Further, the number of myelinated nerve fibers and the condition of the chitosan material was evaluated. Data confirmed that different CNC variants did not induce tissue reaction or negatively impact the condition of the regenerated nerve. At late time points, some specific variants were demonstrated to have resulted in encapsulated material debris in the vicinity of the original implantation side. The reported degradation behavior resembles recent clinical reports and indicates that implantation sites for CNCs need to be chosen carefully. Nerve regeneration itself is undisturbed, but narrow implantation sites should be avoided for eliminating the risk of foreign body sensation with immunologically inert material degradation.

Peripheral nerve injuries significantly impair quality of life due to limited regenerative capacity, which is affected by factors such as neuroma formation, injury severity, scarring, and comorbidities. The Muscle-in-Vein (MIV) repair technique, consisting of a vein filled with skeletal muscle fibers, has emerged as a promising alternative to nerve autografts. This approach supports regeneration by providing growth factors, guiding axonal growth, enhancing Schwann cell migration, and limiting scar and neuroma formation. However, its clinical use is currently restricted mainly to short gaps in sensory digital nerves, and the biological mechanisms underlying its effectiveness remain incompletely understood. In this study, we investigated the role of muscle fibers in the early phases of nerve regeneration, with a particular focus on vascularization. An 8 mm gap in rat median nerves was repaired using the MIV technique and analyzed at 3, 7, 14, and 21 days post-injury. Immunofluorescence analysis demonstrated complete macrophage infiltration and well-organized vascularization throughout the entire graft as early as 7 days post-injury. Consistently, RNA sequencing at early time points revealed significant enrichment of pathways associated with vascular development and identified key angiogenesis-related genes. Notably, our findings indicate partial anastomosis between vessels originating from the nerve stumps and those within the muscle component of the graft. These results suggest that the success of muscle-in-vein nerve repair strategy may be due to an early vascularization process mediated by the synergistic contribution of both muscle and vein.