Developments in tissue engineering yield biomaterials with different supporting strategies to promote nerve regeneration. One promising material is the naturally occurring chitin derivate chitosan. Chitosan has become increasingly important in various tissue engineering approaches for peripheral nerve reconstruction, as it has demonstrated its potential to interact with regeneration associated cells and the neural microenvironment, leading to improved axonal regeneration and less neuroma formation. Moreover, the physiological properties of its polysaccharide structure provide safe biodegradation behavior in the absence of negative side effects or toxic metabolites. Beneficial interactions with Schwann cells (SC), inducing differentiation of mesenchymal stromal cells to SC-like cells or creating supportive conditions during axonal recovery are only a small part of the effects of chitosan. As a result, an extensive body of literature addresses a variety of experimental strategies for the different types of nerve lesions. The different concepts include chitosan nanofibers, hydrogels, hollow nerve tubes, nerve conduits with an inner chitosan layer as well as hybrid architectures containing collagen or polyglycolic acid nerve conduits. Furthermore, various cell seeding concepts have been introduced in the preclinical setting. First translational concepts with hollow tubes following nerve surgery already transferred the promising experimental approach into clinical practice. However, conclusive analyses of the available data and the proposed impact on the recovery process following nerve surgery are currently lacking. This review aims to give an overview on the physiologic properties of chitosan, to evaluate its effect on peripheral nerve regeneration and discuss the future translation into clinical practice.

Background: Peripheral nerve lesions are associated with debilitating long-term consequences. Albeit being essential for evidence-based clinical decision making, epidemiological and etiological data are scarce. We therefore aimed to comprehensively analyze epidemiological and etiological factors of peripheral nerve lesions in one of the largest cohorts. Methods: We screened a total of 110,667 patients treated at our level I trauma center between January 2012 and July 2020 for nerve lesions. Subsequently, demographics, etiologies, concomitant injuries, and lesion characteristics were analyzed. Results: A total of 5026 patients, predominantly young males suffering from non-work-related nerve injuries, were treated. Proximal levels of injury were more likely to be accompanied by fractures, whereas more distal injuries with concomitant vessel or tendon injury. Main causes were 54.6% lacerations. Acute traumatic nerve injury was treated within 24 h in 55.9% of cases. Conclusions: Given the young age of affected patients, early diagnosis and treatment in specialized centers may facilitate their early return to work and improve long-term functional outcomes. The data show the importance of a special attention on nerve injuries, which may be masked by large accompanying injuries. New findings on lesion characteristics of selected subgroups and accompanying circumstances can support a change in treatment strategies.

Introduction: If tensionless nerve coaptation is not possible, bridging the resulting peripheral nerve defect with an autologous nerve graft is still the current gold standard. The concept of conduits as an alternative with different materials and architectures, such as autologous vein conduits or bioartificial nerve conduits, could not replace the nerve graft until today. Chitosan, as a relatively new biomaterial, has recently demonstrated exceptional biocompatibility and material stability with neural lineage cells. The purpose of this prospective randomized clinical experiment was to determine the efficacy of chitosan-based nerve conduits in regenerating sensory nerves in the hand. Materials and methods : Forty-seven patients with peripheral nerve defects up to 26 mm distal to the carpal tunnel were randomized to receive either a chitosan conduit or an autologous nerve graft with the latter serving as the control group. Fifteen patients from the conduit group and seven patients from the control group were available for a 12-month follow-up examination. The primary outcome parameter was tactile gnosis measured with two-point discrimination. The secondary outcome parameters were Semmens Weinstein Monofilament Testing, self-assessed pain, and patient satisfaction. Results: Significant improvement (in static two-point discrimination) was observed six months after trauma (10.7 ± 1.2 mm; p < 0.05) for chitosan-based nerve conduits, but no further improvement was observed after 12 months of regeneration (10.9 ± 1.3 mm). After six months and twelve months, the autologous nerve graft demonstrated comparable results to the nerve conduit, with a static two-point discrimination of 11.0 ± 2.0 mm and 7.9 ± 1.1 mm. Semmes Weinstein Filament Testing in the nerve conduit group showed a continuous improvement over the regeneration period by reaching from 3.1 ± 0.3 after three months up to 3.7 ± 0.4 after twelve months. Autologous nerve grafts presented similar results: 3.3 ± 0.4 after three months and 3.7 ± 0.5 after twelve months. Patient satisfaction and self-reported pain levels were similar between the chitosan nerve conduit and nerve graft groups. One patient required revision surgery due to complications associated with the chitosan nerve tube. Conclusion: Chitosan-based nerve conduits are safe and suitable for bridging nerve lesions up to 26 mm in the hand. Tactile gnosis improved significantly during the early regeneration period, and functional outcomes were similar to those obtained with an autologous nerve graft. Thus, chitosan appears to be a sufficient substitute for autologous nerve grafts in the treatment of small nerve defects in the hand.

Background: Peripheral nerve pathology is frequently encountered in clinical practice among peripheral nerve and extremity surgeons. One major factor limiting nerve regeneration and possibly leading to revision surgeries is the development of traumatic or postoperative adhesions and scarring around nerves. In experimental models, different materials have been studied to limit scar tissue formation when wrapped around nerves. Methods: A systematic review of studies describing nerve-wrapping materials in a non-transectional rat sciatic nerve model was performed following the PRISMA guidelines. Literature describing nerve-wrapping methods for the prevention of peripheral nerve scarring in rat sciatic nerve models was identified using PubMed and Web of Science, scanned for relevance and analyzed. Results: A total of 15 original articles describing 23 different materials or material combinations for nerve wrapping were included. The heterogeneity of the methods used did not allow a meta-analysis, thus, a systematic review was performed. Out of 28 intervention groups, 21 demonstrated a preventive effect on scar tissue formation in at least one qualitative or quantitative assessment method. Conclusions: The analyzed literature describes a variety of materials from different origins to limit peripheral nerve scarring and adhesions. Thus, a scar-preventive effect by wrapping peripheral nerves as adhesion prophylaxis seems likely. However, a quantitative comparison of the studies to identify the optimal material or technique is not possible with the diversity of used models and study designs. Therefore, further research needs to be performed to identify the optimal nerve wraps to be used routinely in clinical practice.

Background: Robotic-assisted peripheral nerve surgery (RASPN) has emerged as a promising advancement in microsurgery, offering enhanced precision and tremor reduction for nerve coaptations. This study investigated the largest published patient collective in RASPN and provided specific technical aspects, operative setups, and a learning curve. Methods: Data collection involved creating a prospective database that recorded surgical details such as surgery type, duration, nerve coaptation time, and number of stitches. The experienced surgeon first underwent a 12-hour training program utilizing the Symani robot system in combination with optical magnification tools before using the system clinically. Results: The study included 19 patients who underwent robot-assisted peripheral nerve reconstruction. The cohort included six men (31.6%) and 13 women (68.4%), with an average age of 53.8 ± 18.4 years. The procedures included nerve transfers, targeted muscle reinnervation, neurotized free flaps, and autologous nerve grafts. Learning curve analysis revealed no significant reduction in time per stitch over the initial nine coaptations (4.9 ± 0.5 min) compared with the last 10 coaptations (5.5 ± 1.5 min). Conclusions: The learning curve for RASPN was compared with early experiences with other surgical robots, emphasizing the importance of surgical proficiency and assistant training. Obstacles such as instrument grip strength and blood clot formation were highlighted, and suggestions for future advancements were proposed. RASPN presents an exciting opportunity to enhance precision; however, ongoing research and optimization are necessary to fully harness its benefits.