JOURNAL/nrgr/04.03/01300535-202603000-00045/figure1/v/2025-06-16T082406Z/r/image-tiff Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge. Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity, highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury; however, its role in modulating neuroinflammation post-peripheral nerve injury remains unknown. Here, we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms. Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel, we evaluated structural and functional recovery, macrophage phenotype alteration, specific cytokine expression, and changes in related signaling molecules in vivo . Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium. These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages. Additionally, porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro . Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway, providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.

The FDA's recent approval of pafolacianine, the first molecular targeted contrast agent for fluorescence-guided surgery (FGS), signifies a remarkable milestone in precision medicine. This advance offers new hope for cancer patients by enabling guided removal of cancerous tissues, where completed surgical removal remains a consistent challenge without real-time intraoperative guidance. For optimal surgical outcomes, delicate nerve tissues must be preserved to maintain patient quality of life. Despite advances in the clinical translation pipeline, the development of clinically viable nerve-specific contrast agents for FGS remains a significant challenge. Herein, a medicinal chemistry-based matrix design strategy was applied to effectively generate a synthetic roadmap permitting management of nerve-specificity within the near-infrared (NIR) oxazine fluorophore family. Many of these newly developed fluorophores demonstrated robust nerve-specificity and superior safety profiles, while also offering spectral profiles that are compatible with the clinical surgical FGS infrastructure. Notably, improving observed brightness in vivo enabled exceptional visibility of buried nerve tissue, a priority during surgical procedures. Critically, the lead probe showed a large dosage safety window capable of generating substantial contrast at doses 100x lower than the maximum tolerated dose. Following clinical translation, such NIR nerve-specific fluorophores stand poised to significantly improve outcomes for surgical patients by improving identification and visualization of surface and buried nerve tissues in real time within the surgical arena.

To create functional neuronal circuit units during nervous system development and/or regeneration, axons are subjected to guidance signals. Expression of these signals occurs in spatiotemporal variations and is translated by the growth cone into a pathway to reach the connecting target which can be a neuron or a non-neuronal cell such as a muscle cell. This path is generated by interactions with the surrounding environment such as cells or the extracellular matrix, a complex molecular substrate. Understanding the interactions with this last component is essential to stimulate nerve regeneration in the context of motor peripheral nerve trauma, the most common source of disabilities, increasing with aging. The goal is to mimic its composition and specific characteristics using innovative biomaterials and/or implants. This review highlights some aspects of the recent findings in nerve repair. After an introduction to the peripheral nervous system, we present an overview of nerve degeneration and regeneration mechanisms before detailing the strategies used nowadays to optimize nerve (re)growth with a specific focus on the use of electric field. We discuss the advantages and limits of each option in terms of therapeutic applications.

Primary neurorrhaphy is the preferred reconstruction modality over nerve grafting, especially for motor nerves. The main limitation to primary repair is often dictated by tension secondary to increased nerve defect length. A retrospective review was conducted on sharp transections of mixed motor and purely sensory nerves in the upper extremity to assess factors influencing defect length. Two groups of either primary repair or nerve graft/conduit were created for comparison. Overall, 71 injured mixed motor nerves and 224 injured sensory nerves were included in the analysis. There were no significant differences in patient demographics between the groups. The primary repair group had a significantly shorter time interval between injury and surgical fixation when compared to the conduit/graft group. Conduit or graft technique was associated with a significantly larger tissue gap after preparation of the nerve ends. Our data suggest that the optimal time for primary repair is within 3 days after injury for mixed nerves and within 7 days for purely sensory nerves. A total of 167 nerve reconstructions were included in a random forest plot, which demonstrated nerve defect size to be influenced by days from injury, type of nerve injured, age, and hypertension. A publicly available 4-feature calculator, nerve evaluation and retraction variability estimator-NERVE, was developed from the forest plot to predict a patient's nerve deficit of ± 3.78 mm on an average, R2=0.89. This calculator could aid surgeons with surgical planning by estimating the potential need of grafts or conduits for reconstruction.

Peripheral nerve injuries (PNI) cause a partial or total deficit of sensory and motor function, producing neuropathic pain and loss of productivity in adults. Type I collagen polymerized with polyvinylpyrrolidone (CLG-PVP) has been used previously in other fibrosing diseases due to its regulatory effects on interleukins, cytokines, and adhesion molecules. In the present study, we describe the role of CLG-PVP in the repair of PNI. We used a murine model of PNI through axonotmesis of the sciatic nerve. CLG-PVP treatments were administered in situ and intramuscularly and were compared to a sham procedure and placebo. Histological and histochemical-specific stain evaluations were performed to describe the structural changes in nervous tissue. A significant reduction in tissue fibrosis was observed in the groups treated with CLG-PVP, especially with the intramuscular treatment. Likewise, an increase in the organization of external lamina and nerve remyelination was observed in the treated groups. In addition, a slight improvement in gait was noted in the treated animal groups at the end of the study. After peripheral nerve injury, CLG-PVP restores the nerve's function, structure, and tissue organization. These therapeutic effects were more evident through the intramuscular administration scheme with a weekly dosage. However, randomized controlled clinical trials should be performed to verify its beneficial effects and characterize adverse events.

Schwann cells (SCs) can potentially transform into the repair-related cell phenotype after injury, which can promote nerve repair. Ferroptosis occurs in the SCs of injured tissues, causing damage to the SCs and exacerbating nerve injury. Targeting ferroptosis in SCs is a promising therapeutic strategy for effective repair; however, research on ferroptosis in the peripheral nervous system remains limited. In this study, we generated and characterized novel distinctive carbon dots, mung bean-derived carbon dots (MB-CDs). Our results demonstrated that MB-CDs have the advantages of low toxicity, good biocompatibility, high stability, the specific effect of ferric ions (Fe3+) on fluorescence, and antioxidant activity. We demonstrated that MB-CDs promoted functional recovery after peripheral nerve injury (PNI), preventing gastrocnemius atrophy. Further research indicated that MB-CDs boosted the repair-related phenotypes of SCs. We used lipopolysaccharide (LPS) to induce an inflammatory model of SCs and co-cultured them with MB-CDs. Then, we examined the effects of MB-CDs by dividing the cells into four groups: the control group (CTRL), MB-CD treatment group (CDs-SCs), LPS treatment group (LPS-SCs), and LPS and MB-CD treatment group (LPS-CDs). RNA sequencing of LPS-CDs and LPS-SCs indicated that LPS-CDs significantly upregulated heme oxygenase-1 (HO-1) expression. Furthermore, western blotting and immunofluorescence techniques demonstrated that MB-CDs suppressed the ferroptosis of SCs via the Nrf2/HO-1/GPX4 signaling pathway after PNI. Overall, this study further uncovered the connection between ferroptosis and the repair-related phenotypes of SCs, filling this gap in the existing knowledge; accordingly, they may be promising agents for treating PNI.

This study aimed to determine the accuracy of ultrasound (US) and MRI compared to intraoperative findings in patients who underwent surgery for their common peroneal nerve (CPN) injury.

Patients who underwent surgical management of a CPN injury with preoperative US were reviewed. The status of the CPN as interpreted by the radiologist in the preoperative US and MRI were recorded. The intraoperative findings of the CPN were compared to the imaging findings. The CPN was classified as intact, partial injury, or complete transection. The location of the injury, and presence of a neuroma-in-continuity or stump neuroma were recorded. The sensitivity and specificity of US for diagnosis of a complete transection and an intact CPN were calculated.

Thirteen patients were included in this study. Preoperative US accurately diagnosed a complete transection in 3 out of 4 patients and an intact CPN in 4 out of 5 patients. MRI did not accurately identify the status of the CPN in any patients. US had 75% sensitivity and 78% specificity for detecting complete transection, and 80% sensitivity and 63% specificity for detecting an intact CPN. The level of injury was correctly identified in 7 out of 13 cases by US and 1 out of 8 cases by MRI. A neuroma was correctly identified in 7 of 11 cases by US and 1 out of 8 cases by MRI.

US has a high sensitivity and specificity when diagnosing CPN lesions and was more accurate than MRI.

This study aimed to assess the efficacy of Quality and Quantity media-cultured mononuclear cells (QQ-MNCs) for promoting nerve regeneration in a mouse sciatic nerve transection model. Human peripheral blood mononuclear cells (PB-MNCs) and QQ-MNCs derived from healthy volunteers were used/compared. The left sciatic nerve was surgically transected in 27 mice. After complete nerve transection was confirmed, end-to-end direct epineurial nerve repair was performed using 9-0 nylon. Fibrin glue was applied to the tissue around the injury site to limit diffusion of the study treatment followed by application of 0.5 ml phosphate buffered saline (PBS) or PB-MNCs (2x106 cells) or QQ-MNCs (2x106 cells) to the injury site. The skin was then closed using 6-0 nylon. Histomorphology, immunohistochemistry, electrophysiologic examination, and functional assessment were evaluated at 12-weeks followed by euthanasia and subsequent harvesting of the left sciatic nerves and the left and right gastrocnemius muscles for examination. QQ-MNCs mice exhibited significant improvement in all histomorphologic parameters (axon fiber diameter, myelin thickness, percentage of nerve density) and immunohistochemistry assays (S100, SOX10, GFAP, neurofilament, IL-1β, VEGF, anti-HNA, TNF-α, vWF) compared to PBS mice (all p < 0.05). QQ-MNCs mice also had a significantly higher Basso Mouse Scale score compared to PBS mice (p = 0.018). The percentage of nerve density adjacent to the injury site was significantly higher in QQ-MNCs mice than in PB-MNCs mice (p = 0.049). IL-1β expression was significantly lower in QQ-MNCs mice than in PB-MNCs mice (p = 0.01). QQ-MNCs mice demonstrated significantly better functional and histomorphologic outcomes of nerve regeneration compared to PB-MNCs mice and PBS mice.

Peripheral nerve injuries are major causes of disability worldwide. The current standard treatment, autologous nerve grafting, puts the donor region at risk and has limited availability. A systematic search of MEDLINE, EMBASE, and Web of Science databases for studies published between January 1, 2008, and September 04, 2024, was performed to compare interventions using chitosan tubes with non-intervention or autologous nerve grafts in rats with artificially injured sciatic nerves. Twenty-one experimental studies including 738 animals were selected. Nerve repair using chitosan conduits resulted in a higher sciatic functional index compared to non-intervention. Higher conduction velocity and a greater number of myelinated fibers were observed in nerve fibers treated with chitosan compared to the no intervention or primary repair groups. However, compound muscle action potentials and somatosensory evoked potentials were superior in the latter compared to nerves treated with the polymer.

Long nerve defects are typically reconstructed with autograft or processed acellular nerve allograft (PNA). PNA is convenient and avoids donor morbidity but lacks the neurotrophic environment of autograft. Increased levels of neurotrophic factors have been identified in pseudomembranes induced around silicone implanted between nerve ends. This study aimed to determine if pseudomembrane can be reliably induced around silicone implanted between nerve ends, and if this enhances regeneration of PNA inset within using a staged technique.

Lewis rats (n = 24) underwent resection of a 15-mm sciatic nerve. The defect was filled with a silicone tube (n = 12) (MA) or the nerve ends were secured to a muscle bed (n = 12) (NMA). After 4 weeks, the silicone was replaced with PNA threaded within the pseudomembrane tunnel. In both groups, PNA was used to reconstruct the nerve defect. Weekly neuromotor assessment was performed with sciatic function index (SFI). At 16 weeks, muscle recovery was assessed, and nerve samples were obtained for histomorphometry.

The MA group's average normalized muscle weight was 46.25% versus the NMA group's 33.19% (p < 0.05). The MA group's average normalized muscle girth was 78.25% versus the NMA group's 60.73% (p < 0.05). Axon counts, g-ratio, and muscle force were not statistically different. At Week 15, the MA group had a significantly higher average SFI: -82.25 versus the NMA group -95.03 (p < 0.05).

PNA inset within induced pseudomembrane sheath enhanced muscle reinnervation. A staged membrane enhancement technique may be effective for improving PNA efficacy in peripheral nerve injury reconstruction.

Peripheral nerve injuries are a major clinical challenge because of their complex nature and limited regenerative capacity. This study aimed to improve peripheral nerve regeneration using Wharton's jelly mesenchymal stem cells (WJ-MSCs) engineered to express brain-derived neurotrophic factor (BDNF) via a baculovirus (BV) vector. The cells were evaluated for efficacy when seeded into acellular nerve grafts (ANGs) in a rat sciatic nerve defect model.

WJ-MSCs were transfected with recombinant BV to upregulate BDNF expression. Conditioned medium (CM) from these cells was utilized to treat Schwann cells (SCs), and the impact on myelination-related markers, including KROX20, myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β), and the activation of the mammalian target of rapamycin (mTOR)/ protein kinase B (AKT)/p38 signaling pathways were evaluated. In vivo, BDNF-expressing WJ-MSCs were seeded into ANGs and implanted into a rat sciatic nerve defect model. Functional recovery was evaluated via video gait analysis, isometric tetanic force measurement, muscle weight evaluation, ankle contracture angle measurement, and histological analysis using toluidine blue staining.

BDNF expression was significantly upregulated in WJ-MSCs post-transfection. BDNF-MSC CM substantially promoted the expression of myelination markers in SCs and activated the mTOR/AKT/p38 signaling pathway. In the rat model, seeding of ANGs with BDNF-expressing WJ-MSCs resulted in improved functional outcomes, including enhanced toe-off angles, increased isometric tetanic force, greater muscle weight recovery, and a higher total number of myelinated axons compared with controls.

WJ-MSCs engineered to express BDNF significantly enhanced peripheral nerve regeneration when utilized in conjunction with ANGs. These findings indicate BDNF-expressing WJ-MSCs are a promising therapeutic approach for treating peripheral nerve injuries.

Peripheral nerve injury is a significant clinical challenge, often leading to permanent functional deficits. Standard interventions, such as autologous nerve grafts or distal nerve transfers, require sacrificing healthy nerve tissue and typically result in limited motor or sensory recovery. Nerve regeneration is complex and influenced by several factors: 1) the regenerative capacity of proximal neurons, 2) the ability of axons and support cells to bridge the injury, 3) the capacity of Schwann cells to maintain a supportive environment, and 4) the readiness of target muscles or sensory organs for reinnervation. Emerging bioengineering solutions, including biomaterials, drug delivery systems, fusogens, electrical stimulation devices, and tissue-engineered products, aim to address these challenges. Effective translation of these therapies requires a deep understanding of the physiology and pathology of nerve injury. This article proposes a comprehensive framework for developing restorative strategies that address all four major physiological responses in nerve repair. By implementing this framework, we envision a paradigm shift that could potentially enable full functional recovery for patients, where current approaches offer minimal hope.

A peripheral nerve injury is a great burden for the patient and a challenge for the clinician. In a complete injury (axonotmesis or neurotmesis), the slow nature of nerve regeneration after repair or reconstruction hardly catches up to the target organ's degeneration rate, leading to a poor prognosis. The current advance in regenerative medicine has shown the potency of stem cells and their products for healing many human body structures, including the nerve. A comprehensive literature search was conducted using an internet-based search engine for current advances in regenerative medicine to augment peripheral nerve repair or reconstruction. Stem cells can differentiate into nerve cells and have paracrine and immunomodulatory effects. Its products, such as the secretome and exosome, have also been studied, and they have many benefits for the regeneration process. This novel treatment possesses significant potential to accelerate nerve healing after nerve reconstruction and potentially postpone the degenerative process in the target organ, allowing it to respond to the new signal once nerve regeneration is complete. The aim of this article is to summarized the application of stem cells and its products for nerve healing.

Quantifying peripheral nerve regeneration via electrophysiology is a commonly used technique, but it can be complicated by spurious electrical activity. This study sought to compare electrode configurations for measuring compound muscle action potential (CMAP) of the tibialis anterior (TA) muscle in a rat model for specific and sensitive detection of regeneration of peroneal nerve to the TA.

10 Sprague-Dawley rats underwent a peroneal nerve transection with direct microsuture repair. CMAPs were conducted with different placements and types of electrodes. Compound action potentials (CAPs) and gait analysis were regularly collected up to 70 days (d) post operation (PO). Nerve sections were harvested at 49 d (n = 4) and 70 d (n = 6) PO and stained with toluidine blue to assess nerve morphometry.

Of the tested configurations for CMAPs, a concentric recording/reference electrode in combination with stimulation from the sciatic notch showed the least background and highest sensitivity, while some configurations showed significant noise and did not detect changes in CMAPs within the 70 d recording period following injury. CAPs, gait analysis, morphometry, and muscle mass support the extent of regeneration indicated by CMAPs collected with concentric electrodes.

Collateral innervation patterns can complicate CMAP recordings as signals from adjacent muscles can be detected and misinterpreted as regeneration. The outcome of this study shows how differences in configurations and electrodes have significant effects on CMAP for the TA. The results identify methods using concentric electrodes that provide high specificity and sensitivity capable of detecting evidence of regeneration early after injury.

Devices used for diagnosing disease are often large, expensive, and require operation by trained professionals, which can result in delayed diagnosis and missed opportunities for timely treatment. However, wearable devices are being recognized as a new approach to overcoming these difficulties, as they are small, affordable, and easy to use. Recent advancements in wearable technology have made monitoring information possible from the surface of organs like the skin and eyes, enabling accurate diagnosis of the user's internal status. In this review, we categorize the body's organs into external (e.g., eyes, oral cavity, neck, and skin) and internal (e.g., heart, brain, lung, stomach, and bladder) organ systems and introduce recent developments in the materials and designs of wearable electronics, including electrochemical and electrophysiological sensors applied to each organ system. Further, we explore recent innovations in wearable electronics for monitoring of deep internal organs, such as the heart, brain, and nervous system, using ultrasound, electrical impedance tomography, and temporal interference stimulation. The review also addresses the current challenges in wearable technology and explores future directions to enhance the effectiveness and applicability of these devices in medical diagnostics. This paper establishes a framework for correlating the design and functionality of wearable electronics with the physiological characteristics and requirements of various organ systems.

Motor recovery following nerve injury is dependent on time required for muscle reinnervation. This process is imperfect, however, and recovery is often incomplete. At the neuromuscular junction (NMJ), macrophage signaling aids muscle reinnervation. Tacrolimus (FK506) treatment speeds functional recovery through unknown mechanisms. This study investigated whether macrophages were required for FK506 neuroenhancing effects.

Wildtype (WT) mice and mice with impaired macrophage recruitment to injury sites (Ccr2 -/- ) were injected subcutaneously with either saline or FK506 for 3 days prior to sciatic nerve transection and immediate repair and then daily for 4 weeks. Functional recovery was assessed by grid walk and muscle force. Morphometric NMJ and macrophage analyses were conducted in extensor digitorum longus muscles.

FK506-injected WT mice showed increased proportions of fully reinnervated NMJs and terminal Schwann cells/NMJ (p < 0.05), improved recovery of tetanic muscle force (p < 0.05), and improved grid walking (p < 0.05) relative to controls. Ccr2 -/- mice showed no enhancements in recovery; Ccr2 -/- mice treated with FK506 did not differ from controls on any tested metric. We also observed at the NMJ of WT mice increased macrophage numbers with FK506 treatment and increased macrophages expressing FK506 binding protein, FKBP52, after nerve injury.

These results show that macrophages are required for FK506-mediated improvements in NMJ reinnervation and muscle function. These data implicate macrophages in the mechanism underlying FK506-mediated enhancement of motor recovery after nerve injury. Enhanced knowledge of the neuroenhancing mechanism of FK506 may identify new clinically relevant therapeutic targets.

Activation of Sirtuin 1 (SIRT-1) is vital for axonogenesis and nerve regeneration. Caloric restriction (CR) has health benefits and protects against neurodegenerative disorders, largely through SIRT-1 regulation. This study investigates how diet control impacts peripheral nerve injury, focusing on SIRT-1 expression. We prepared nerve tissue cultures for a pharmacological analysis of SIRT-1's effects on nerve degeneration. After two weeks of 70% caloric restriction, we crushed the left sciatic nerve of Sprague-Dawley rats with a vessel clamp. We then administered SIRT-1 agonists or antagonists intraperitoneally. Nerve explant cultures showed increased SIRT-1 expression with SRT-1720, which was reduced by EX527, indicating enhanced regeneration. In the animal study, diet control led to notable SIRT-1 expression in plasma. This expression increased with SIRT-1 agonists and decreased with antagonists. SIRT-1 levels in paw skin were strongly correlated with PGP 9.5 and collagen deposition, while nerve fiber size and regeneration markers (S-100 and NF) also correlated with SIRT-1 expression. Inflammatory markers showed an inverse relationship with SIRT-1. TNF-α and NGF in the dorsal root ganglion responded reciprocally to SIRT-1 expression. Increased acetylcholine receptors and desmin in denervated muscle were parallel to SIRT-1 levels, with similar trends observed in muscle weight and diameter. Neurobehavioral and electrophysiological results aligned with these measurements. Caloric restriction has a preventative effect on nerve damage, mainly through SIRT-1 modulation. From a health perspective, promoting caloric restriction is important for mitigating nerve injury severity.

Imaging plays an important role in evaluating peripheral nerves. In the preoperative setting, imaging helps overcome pitfalls of electrodiagnostic testing and provides key anatomical information to guide surgical management. In the postoperative setting, imaging also offers key information for treating physicians, although it comes with several challenges due to postsurgical changes and alteration of normal anatomy. This article reviews our approach to peripheral nerve imaging, including how we use imaging in the pre- and postoperative setting for several common indications.

Synaptogenesis requires complex coordination between the terminating motor neuron and the developing myofiber endplate. Cross-talk research has focused on in vivo models or singular treatments with known signaling molecules identified from these animal studies. However, in vivo models are inefficient at measuring dynamic signaling changes due to assay resolution and cost. Further, despite advances in culture methods relying on microfluidic platforms, much remains unknown about the dynamic cross-talk between these two key cell types. As such, there is an unmet investigation into simple and reproducible coculture studies. In this study, we characterize both myoblast (C2C12) and motor neuron (NSC-34) changes that occur in either a conditioned media model, a transwell coculture, and a 2D migration coculture. We successfully demonstrate repeatable changes in synaptogenesis with ~38% increase in Chrng protein levels (p < 0.05) in each model, increased myotube alignment in cocultured myoblasts measured with FFT analysis, and show motor neurons are preferentially chemo-attracted to myotubes without the use of neurite-path constraining microfluidics. Lastly, we identified a potential new signaling protein responsible for motor endplate development, apolipoprotein E (ApoE). This coculture approach reveals changes to myotube myogenesis and synaptogenesis providing a consistent platform for cross-talk and pathway analysis for future studies.

The mechanical behaviour of peripheral nerves is known to vary between different nerves and nerve regions. As the field of nerve tissue engineering advances, it is vital that we understand the range of mechanical regimes future nerve implants must match to prevent failure. Data on the mechanical behaviour of human peripheral nerves are difficult to obtain due to the need to conduct mechanical testing shortly after removal from the body. In this work, we adapt a 3D multiscale biomechanical model, developed using asymptotic homogenisation, to mimic the micro- and macroscale structure of a peripheral nerve. This model is then parameterised using experimental data from rat peripheral nerves and used to investigate the effect of varying the collagen content, the fibril radius and number density, and the macroscale cross-sectional geometry of the peripheral nerve on the effective axial Young's moduli of the whole nerve. Our results indicate that the total amount of collagen within a cross section has a greater effect on the axial Young's moduli compared to other measures of structure. This suggests that the amount of collagen in a cross section of a peripheral nerve, which can be measured through histological and imaging techniques, is one of the key metrics that should be recorded in the future experimental studies on the biomechanical properties of peripheral nerves.

Peripheral nerve injury (PNI) is characterized by a loss of cellular and axonal integrity, often leading to limited functional recovery and pain. Many PNIs are not amenable to repair with traditional techniques; however, cell therapies, particularly Schwann cells (SCs), offer the promise of neural tissue replacement and functional improvement. Exosomes, which carry cellular signaling molecules, can be secreted by SCs and have shown promise in PNI. Our laboratory has had success using SCs in preclinical and clinical treatment settings. Transplanted cells have several known limitations, which exosomes mitigate. To that end, the current study investigated if implanted SC-derived exosomes in conduits, conduits with SCs, reverse autograft, or empty conduits comparably improve axonal regeneration and pain outcomes 16-weeks after repair of a long gap PNI in adult rats. Results show that there were no differences between groups in the von Frey filament testing or in the Hargreaves test. Electrophysiological testing showed a significant difference between the injured (ipsilateral) and uninjured (contralateral) limbs while histological assessment showed a significant difference between axonal counts in different areas of the conduit. Based on the results of the current study, more research is needed to understand the therapeutic role of exosomes in PNI.

 Pedicled, prefabricated, and free nerve flaps have several drawbacks, such as requiring microsurgical anastomosis, the need for secondary operations and the risk of developing thrombosis. In this study, we aimed to vascularize the repaired nerve in a single session by establishing a connection between the epineurium of the repaired median nerve and the tunica adventitia of the brachial artery.

 The technique was performed on the median nerves of a total of 42 rats over 13 weeks. While group 1 didn't receive any intervention, the following three groups (2, 3, and 4) received classic treatments (coaptation, graft, and vein conduit). In addition to classic treatments, the other three groups (5, 6, and 7) were vascularized by attaching the adventitia of the brachial artery to the repaired nerves. Nerve regeneration was evaluated using functional tests, immunohistochemical analysis, and electron microscope.

 The vascularized groups (5, 6, and 7) showed earlier functional recovery (p < 0.05). Vascularization reduced inflammation in the coaptation group, reduced fibrosis and degeneration in the nerve graft group, and reduced fibrosis, degeneration and disorganization while increased the number of passing fibers and myelination in the vein conduit group (p < 0.05). Vascularization provided superior ultrastructural findings. Microscopic analysis revealed a novel finding of "zone of neurovascular interaction" between the adventitia and the regenerating nerve.

 Vascularizing the repaired nerves with this new technique provided faster functional and better histological healing. Unlike classic vascularization techniques, this method does not require microsurgical anastomosis, does not carry the risk of thrombosis, and does not necessitate secondary operations. The "zone of neurovascular interaction" identified in this study revealed regenerating axon clusters alongside newly developed blood vessels. This important finding highlights a potential role of the tunica adventitia in nerve regeneration.

ATP synthase inhibitory factor 1 (ATPIF1), a key modulator of ATP synthase complex activity, has been implicated in various physiological and pathological processes. While its role is established in conditions such as hypoxia, ischemia-reperfusion injury, apoptosis, and cancer, its involvement remains elusive in peripheral nerve regeneration. Leveraging ATPIF1 knockout transgenic mice, this study reveals that the absence of ATPIF1 impedes neural structural reconstruction, leading to delayed sensory and functional recovery. RNA-sequencing unveils a significant attenuation in immune responses following peripheral nerve injury, which attributes to the CCR2/CCL2 signaling axis and results in decreased macrophage infiltration and activation. Importantly, macrophages, not Schwann cells, are identified as key contributors to the delayed Wallerian degeneration in ATPIF1 knockout mice, and affect the overall outcome of peripheral nerve regeneration. These results shed light on the translational potential of ATPIF1 for improving peripheral nerve regeneration.

The goal of managing patients with peripheral nerve injuries is to improve how a patient feels and functions. This goal is best assessed with patient-reported outcome measures (PROMs), which elicit patient concerns, treatment goals, and clinical progression. This study reviews existing PROMs for adult patients with peripheral nerve injuries to assess how comprehensively they measure outcomes important to patients.

A systematic review of Ovid MEDLINE, Scopus, Web of Science, and Embase (from inception to August 13, 2022) was conducted to identify PROMs developed for adult patients with peripheral nerve injuries. Studies were included if (1) the study population involved traumatic or acquired peripheral nerve injuries; (2) they were randomized controlled trials, cohort studies, or single-arm observational studies; (3) participants were 18 years or older; and (4) PROMs were used to assess quality of life or patient satisfaction.

A total of 378 studies were included in this systematic review. We identified 141 unique PROMs used in the adult peripheral nerve injury literature: 20 are disease-specific (14%), 10 are function-specific (7%), 19 are mental health and well-being-specific (13%), 11 are quality of life-specific (8%), 32 are body region-specific (23%), 29 are symptom-specific (21%), 3 are satisfaction-specific (2%), 15 are generic (11%), and 2 are other (1%).

There exists considerable heterogeneity of PROMs used in research on patients with peripheral nerve injuries. None of the PROMs comprehensively assess this patient population. The need for the development of a comprehensive PROM for this patient population is highlighted.

Peripheral nerve injury is common and can have devastating consequences. In severe cases, functional recovery is often poor despite surgery. This is primarily due to the exceedingly slow rate of nerve regeneration at only 1-3 mm/day. The local environment in the distal nerve stump supportive of nerve regrowth deteriorates over time and the target end organs become atrophic. To overcome these challenges, investigations into treatments capable of accelerating nerve regrowth are of great clinical relevance and are an active area of research. One intervention that has shown great promise is perioperative electrical stimulation. Postoperative stimulation helps to expedite the Wallerian degeneration process and reduces delays caused by staggered regeneration at the site of nerve injury. By contrast, preoperative "conditioning" stimulation increases the rate of nerve regrowth along the nerve trunk. Over the past two decades, a rich body of literature has emerged that provides molecular insights into the mechanism by which electrical stimulation impacts nerve regeneration. The end result is upregulation of regeneration-associated genes in the neuronal body and accelerated transport to the axon front for regrowth. The efficacy of brief electrical stimulation on patients with peripheral nerve injuries was demonstrated in a number of randomized controlled trials on compressive, transection and traction injuries. As approved equipment to deliver this treatment is becoming available, it may be feasible to deploy this novel treatment in a wide range of clinical settings.

With the integration of bioelectronics and materials science, implantable self-powered systems for electrical stimulation medical devices have emerged as an innovative therapeutic approach, garnering significant attention in medical research. These devices achieve self-powering through integrated energy conversion modules, such as triboelectric nanogenerators (TENGs) and piezoelectric nanogenerators (PENGs), significantly enhancing the portability and long-term efficacy of therapeutic equipment. This review delves into the design strategies and clinical applications of implantable self-powered systems, encompassing the design and optimization of energy harvesting modules, the selection and fabrication of adaptable electrode materials, innovations in systematic design strategies, and the extensive utilization of implantable self-powered systems in biological therapies, including the treatment of neurological disorders, tissue regeneration engineering, drug delivery, and tumor therapy. Through a comprehensive analysis of the latest research progress, technical challenges, and future directions in these areas, this paper aims to provide valuable insights and inspiration for further research and clinical applications of implantable self-powered systems.

Improved treatment options are urgently needed for neurological injuries resulting from trauma or iatrogenic events causing long-term disabilities that severely impact patients' quality of life. In vitro and animal studies have provided promising proof-of-concept examples of regenerative therapies using mesenchymal stromal cells (MSC) for a wide range of pathological conditions. Over the previous decade, various MSC-based therapies have been investigated in clinical trials to treat traumatic neurological injuries. However, while the safety and feasibility of MSC treatments has been established, the patient outcomes in these studies have not demonstrated significant success in the translation of MSC regenerative therapy for the treatment of human brain and spinal cord injuries. Herein, we have reviewed the literature and ongoing registered trials on the application of MSC for the treatment of traumatic brain injury, traumatic spinal cord injury, and peripheral nerve injury. We have focused on the shortcomings and technological hurdles that must be overcome to further advance clinical research to phase 3 trials, and we discuss recent advancements that represent potential solutions to these obstacles to progress.

The development of biomaterials such as synthetic scaffolds for peripheral nerve regeneration requires a precise knowledge of the mechanical properties of the nerve in physiological-like conditions. Mechanical properties (Young's modulus, maximum stress and strain at break) for peripheral nerves are scarce and large discrepancies are observed in between reports. This is due in part to the absence of a robust testing device for nerves. To overcome this limitation, a custom-made tensile device (CMTD) has been built. To evaluate its reproducibility and accuracy, the imposed speed and distance over measured speed and distance was performed, followed by a validation using poly(dimethylsiloxane) (PDMS), a commercial polymer with established mechanical properties. Finally, the mechanical characterization of rodents (mice and rats) sciatic nerves using the CMTD was performed. Mouse and rat sciatic nerves Young's modulus were 4.57 ± 2.04 and 19.2 ± 0.86 MPa respectively. Maximum stress was 1.26 ± 0.56 MPa for mice and 3.81 ± 1.84 MPa for rats. Strain at break was 53 ± 17% for mice and 32 ± 12% for rats. The number of axons per sciatic nerve was found to be twice higher for rats. Statistical analysis of the measured mechanical properties revealed no sex-related trends, for both mice and rats (except for mouse maximum stress with p=0.03). Histological evaluation of rat sciatic nerve corroborated these findings. By developing a robust CMTD to establish the key mechanical properties (Young's modulus, maximum stress and strain at break) values for rodents sciatic nerves, our work represent an essential step toward the development of better synthetic scaffolds for peripheral nerve regeneration.

Peripheral nerve injury (PNI) poses a significant public health issue, often leading to muscle atrophy and persistent neuropathic pain, which can drastically impact the quality of life for patients. Electrical stimulation represents an effective and non-pharmacological treatment to promote nerve regeneration. Yet, the postoperative application of electrical stimulation remains a challenge. Here, we propose a fully biodegradable, self-powered nerve guidance conduit (NGC) based on dissolvable zinc-molybdenum batteries. The conduit can offer topographic guidance for nerve regeneration and deliver sustained electrical cues between both ends of a transected nerve stump, extending beyond the surgical window. Schwann cell proliferation and adenosine triphosphate (ATP) production are enhanced by the introduction of the zinc-molybdenum batteries. In rodent models with 10-mm sciatic nerve damage, the device effectively enhances nerve regeneration and motor function recovery. This study offers innovative strategies for creating biodegradable and electroactive devices that hold important promise to optimize therapeutic outcomes for nerve regeneration.

The use of ultrasonography to diagnose and manage peripheral nerve injury is not routinely performed, but is an advantageous alternative to magnetic resonance imaging (MRI) in the pediatric population.

The authors report a case of a toddler-aged female who sustained a supracondylar fracture and subsequent median and ulnar nerve injuries. All preoperative and postoperative imaging was performed through high-resolution ultrasound as opposed to MRI. Starting at 6 months post-nerve repair and with 18 months of follow-up, the patient exhibited substantial improvement in motor strength and sensory function. This case demonstrated a successful outcome while providing an imaging alternative that is portable, relatively low-cost, lacks ionizing radiation, provides additional information on vascular integrity, and obviates the need for general anesthetic such as MRI.

The authors conclude that the use of ultrasonography to diagnose and manage traumatic peripheral nerve injury is advantageous, particularly in the pediatric population.

Peripheral nerve injuries (PNIs) pose significant clinical challenges due to their complex healing processes and the often incomplete functional recovery. This review and bibliometric analysis aimed to provide a comprehensive overview of advancements in peripheral nerve regeneration research, focusing on trends, influential studies, and emerging areas. By analyzing 2921 publications from the Web of Science Core Collection, key themes such as nerve regeneration, repair, and the critical role of Schwann cells were identified. The study highlights a notable increase in research output since the early 2000s, with China and the United States leading in publication volume and citations. The analysis also underscores the importance of collaborative networks, which are driving innovation in this field. Despite significant progress, the challenge of achieving complete functional recovery from PNIs persists, emphasizing the need for continued research into novel therapeutic strategies. This review synthesizes current knowledge on the mechanisms of nerve regeneration, including the roles of cellular and molecular processes, neurotrophic factors, and emerging therapeutic approaches such as gene therapy and stem cell applications. Additionally, the study revealed the use of nanotechnology, biomaterials, and advanced imaging techniques, which hold promise for improving the outcomes of nerve repair. This bibliometric analysis not only maps the landscape of peripheral nerve regeneration research but also identifies opportunities for future investigation. This study has some limitations, including reliance on the Web of Science Core Collection, which may exclude relevant research from other databases. The analysis is predominantly English-based, potentially overlooking significant non-English studies. Citation trends might be influenced by shifting research priorities and accessibility issues, affecting the visibility of older work. Additionally, geographical disparities and limited collaboration networks may restrict the global applicability and knowledge exchange in this field.

Despite the importance of timing of nerve surgery after peripheral nerve injury, optimal timing of intervention has not been clearly delineated. The goal of this study is to explore factors that may have a significant impact on clinical outcomes of severe peripheral nerve injury that requires reconstruction with nerve transfer or graft.

Adult patients who underwent peripheral nerve transfer or grafting in Alberta were reviewed. Clustered multivariable logistic regression analysis was used to examine the association of time to surgery, type of nerve repair, and patient characteristics on strength outcomes. Cox proportional hazard regression analysis model was used to examine factors correlated with increased time to surgery.

Of the 163 patients identified, the median time to surgery was 212 days. For every week of delay, the adjusted odds of achieving Medical Research Council strength grade ≥ 3 decreases by 3%. An increase in preinjury comorbidities was associated with longer overall time to surgery (aHR 0.84, 95% CI 0.74-0.95). Referrals made by surgeons were associated with a shorter time to surgery compared to general practitioners (aHR 1.87, 95% CI 1.14-3.06). In patients treated with nerve transfer, the adjusted odds of achieving antigravity strength was 388% compared to nerve grafting; while the adjusted odds decreased by 65% if the injury sustained had a pre-ganglionic injury component.

Mitigating delays in surgical intervention is crucial to optimizing outcomes. The nature of initial nerve injury and surgical reconstructive techniques are additional important factors that impact postoperative outcomes.

Traumatic peripheral nerve injury (PNI), which occurs in up to 3% of trauma patients, is a devastating condition that often leads to permanent disability. However, knowledge of traumatic PNI is limited. We describe epidemiology and clinical characteristics of traumatic PNI in Korea and identify the predictors of traumatic complete PNI.

A list of enlisted soldier patients who were discharged from military service due to PNI over a 10-year period (2012-2021) was obtained, and their medical records were reviewed. Patients were classified according to the causative events (traumatic vs. nontraumatic) and injury severity (complete vs. incomplete). Of traumatic PNIs, we compared the clinical variables between the incomplete and complete PNI groups and identified predictors of complete PNI.

Of the 119 young male patients who were discharged from military service due to PNI, 85 (71.4%) were injured by a traumatic event; among them, 22 (25.9%) were assessed as having a complete injury. The most common PNI mechanism (n=49, 57.6%), was adjacent fractures or dislocations. Several injury-related characteristics were significantly associated with complete PNI: laceration or gunshot wound, PNI involving the median nerve, PNI involving multiple individual nerves (multiple PNI), and concomitant muscular or vascular injuries. After adjusting for other possible predictors, multiple PNI was identified as a significant predictor of a complete PNI (odds ratio, 3.583; P=0.017).

In this study, we analyzed the characteristics of enlisted Korean soldiers discharged due to traumatic PNI and found that the most common injury mechanism was adjacent fracture or dislocation (57.6%). Patients with multiple PNI had a significantly increased risk of complete injury. The results of this study contribute to a better understanding of traumatic PNI, which directly leads to a decline in functioning in patients with trauma.

The restoration of adequate function and sensation in nerves following an injury is often insufficient. Electrical stimulation (ES) applied during nerve repair can promote axon regeneration, which may enhance the likelihood of successful functional recovery. However, increasing operation time and complexity are associated with limited clinical use of ES. This study aims to better assess whether short-duration ES types (voltage mode vs. current mode) are able to produce enhanced regenerative activity following peripheral nerve repair in rat models. Wistar rats were randomly divided into 3 groups: no ES (control), 30-minute ES with a current pulse, and 30-minute ES with a voltage pulse. All groups underwent sciatic nerve transection and repair using a silicone tube to bridge the 6-mm gap between the stumps. In the 2 groups other than the control, ES was applied after the surgical repair. Outcomes were evaluated using electrophysiology, histology, and serial walking track analysis. Biweekly walking tracks test over 12 weeks revealed that subjects that underwent ES experienced more rapid functional improvement than subjects that underwent repair alone. Electrophysiological analysis of the newly intratubular sciatic nerve at week 12 revealed strong motor function recovery in rats that underwent 30-minute ES. Histologic analysis of the sciatic nerve and its tibial branch at 12 weeks demonstrated robust axon regrowth in all groups. Both types of short-duration ES applied during nerve repair can promote axon regrowth and enhance the chances of successful functional recovery.

Magnetic resonance imaging (MRI) is a potentially powerful novel peripheral nerve diagnosis technique. To determine its validity, in-vivo preclinical studies are necessary. However, when using a rodent model, positioning rats and achieving high-resolution images can be challenging. We present a short report that outlines an optimal protocol for positioning rats for in-vivo MRI acquisition. Female Sprague-Dawley rats with sciatic nerve injury were induced into anesthesia using 4% isoflurane in oxygen and maintained at 1.5%. Rats were placed into a plexiglass cradle in a right lateral recumbent position, and a surface coil was placed over the left leg. Respiration rate and body temperature were monitored throughout the scan. Our protocol was successful as rats were able to undergo MRI scanning safely and efficiently. There were no adverse reactions, and clear images of the left sciatic nerve were obtained. Animal positioning took 30 minutes, and 5 different acquisitions were obtained in 2 hours. The total time from anesthesia induction to recovery was under 3 hours. Given the increasing interest in MRI diagnostic techniques, we hope this report aids other researchers studying peripheral nerve injury imaging in rat models.

Recovering from neuromuscular injuries or conditions can be a challenging journey that involves complex surgeries and extensive physical rehabilitation. During this process, individuals often rely on orthotic devices to support and enable movement of the affected limb. However, users have criticized current commercially available powered orthotic devices for their bulky and heavy design. To address these limitations, we developed a novel powered myoelectric elbow orthosis.

The orthosis incorporates 3 mechanisms: a solenoid brake, a Bowden cable-powered constant torque elbow mechanism, and an extension limiter. The device controller and battery are in a backpack to reduce the weight on the affected arm. We performed extensive calculations and testing to ensure that the orthosis could withstand at least 15 Nm of elbow torque. We developed a custom software effectively control the orthosis, enhancing its usability and functionality. A certified orthotist fitted a subject who had undergone a gracilis free functioning muscle transfer surgery with the device. We studied the subject under Mayo clinic IRB no. 20-006849 and obtained objective measurements to assess the orthosis's impact on upper extremity functionality during daily activities.

The results are promising since the orthosis significantly improved elbow flexion range of motion by 40° and reduced compensatory movements at the shoulder (humerothoracic joint) by 50°. Additionally, the subject was able to perform tasks which were not possible before, such as carrying a basket with weights, highlighting the enhanced functionality provided by the orthosis.

In brief, by addressing the limitations of existing devices, this novel powered myoelectric elbow orthosis offers individuals with neuromuscular injuries/conditions improved quality of life. Further research will expand the patient population and control mechanisms.

Anesthetic conditioning has been shown to provide neuroprotection in several neurological disorders. Whether anesthetic conditioning provides protection against peripheral nerve injuries remains unknown. The aim of our current study is to investigate the impact of isoflurane conditioning on the functional outcomes after peripheral nerve injury (PNI) in a rodent sciatic nerve injury model.

Adult male Lewis rats underwent sciatic nerve cut and repair and exposed to none (Group 1, sham), single isoflurane exposure (Group 2), three-time isoflurane exposure (Group 3), and six-time isoflurane exposure (Group 4). Isoflurane conditioning was established by administration of 2% isoflurane for 1 hour, beginning 1-hour post sciatic nerve cut and repair. Groups 3 and 4 were exposed to isoflurane for 1 hour, 3 and 6 consecutive days respectively. Functional outcomes assessed included compound muscle action potential (CMAP), evoked muscle force (tetanic and specific tetanic force), wet muscle mass, and axonal counting.

We observed an increase in axons, myelin width and a decrease in G-ratio in the isoflurane conditioning groups (3- and 6-days). This correlated with a significant improvement in tetanic and specific tetanic forces, observed in both groups 3 and 4.

Isoflurane conditioning (3- and 6-day groups) resulted in improvement in functional outcomes at 12 weeks post peripheral nerve injury and repair in a murine model. Future experiments should be focused on identifying the therapeutic window of isoflurane conditioning and exploring the underlying molecular mechanisms responsible for isoflurane conditioning induced neuroprotection in PNI.

Nerve guidance conduits (NGCs) are widely developed using various materials for the functional repair of injured or diseased peripheral nerves. Especially, hydrogels are considered highly suitable for the fabrication of NGCs due to their beneficial tissue-mimicking characteristics (e.g., high water content, softness, and porosity). However, the practical applications of hydrogel-based NGCs are hindered due to their poor mechanical properties and complicated fabrication processes. To bridge this gap, a novel double-network (DN) hydrogel using alginate and gelatin by a two-step crosslinking process involving chemical-free gamma irradiation and ionic crosslinking, is developed. DN hydrogels (1% alginate and 15% gelatin), crosslinked with 30 kGy gamma irradiation and barium ions, exhibit substantially improved mechanical properties, including tensile strength, elastic modulus, and fracture stain, compared to single network (SN) gelatin hydrogels. Additionally, the DN hydrogel NGC exhibits excellent kink resistance, mechanical stability to successive compression, suture retention, and enzymatic degradability. In vivo studies with a sciatic defect rat model indicate substantially improved nerve function recovery with the DN hydrogel NGC compared to SN gelatin and commercial silicone NGCs, as confirm footprint analysis, electromyography, and muscle weight measurement. Histological examination reveals that, in the DN NGC group, the expression of Schwann cell and neuronal markers, myelin sheath, and exon diameter are superior to the other controls. Furthermore, the DN NGC group demonstrates increased muscle fiber formation and reduced fibrotic scarring. These findings suggest that the mechanically robust, degradable, and biocompatible DN hydrogel NGC can serve as a novel platform for peripheral nerve regeneration and other biomedical applications, such as implantable tissue constructs.

"State of the Art" Learning Objectives: This manuscript serves to provide the reader with a general overview of the contemporary approaches to peripheral nerve reconstruction as the field has undergone considerable advancement over the last 3 decades. The learning objectives are as follows: To provide the reader with a brief history of peripheral nerve surgery and some of the landmark developments that allow for current peripheral nerve care practices.To outline the considerations and management options for the care of patients with brachial plexopathy, spinal cord injury, and lower extremity peripheral nerve injury.Highlight contemporary surgical techniques to address terminal neuroma and phantom limb pain.Review progressive and future procedures in peripheral nerve care, such as supercharge end-to-side nerve transfers.Discuss rehabilitation techniques for peripheral nerve care.

To compare the iatrogenic radial nerve injury (iRNI) rate of different implant (plate vs. intramedullary nail) and surgical approaches during humeral shaft fracture surgery.

The online PubMed database was used to search for articles describing iRNI after humeral fracture with a publication date from Jan 2000 to October 2023. The following types of articles were selected: (1) case series associating with adult humeral shaft fracture, preoperative radial nerve continuity, non-pathological fracture and non-periprosthetic fracture; (2) involving humeral shaft (OTA/AO 12) fractures. Articles where we were unable to judge surgical approach or fracture pattern (OTA/AO 12) were excluded. The data were analyzed by SPSS 27.0 and Chi-square test was performed to identify incidence of iRNI associated with different implant and surgical approaches.

Fifty-four articles with 5063 cases were included, with 3510 cases of the plate, 830 cases of intramedullary nail and 723 cases of uncertain internal fixation. The incidences of iRNI with plate and intramedullary nail were 5.95% (209/3510) and 2.77% (23/830) (p < 0.05). And iRNI incidences of different surgical approaches were 3.7% (3/82) for deltopectoral approach, 5.74% (76/1323) for anterolateral approach, 13.54% (26/192) for lateral approach and 6.68% (50/749) for posterior approach. The iRNI rates were 0.00% (0/33) for anteromedial MIPO, 2.67% (10/374) for anterolateral MIPO and 5.40% (2/37) for posterior MIPO (p > 0.05). The iRNI rates were 2.87% (21/732) for anterograde intramedullary nail and 2.04% (2/98) for retrograde intramedullary nail (p > 0.05). In humeral bone nonunion surgery, the rate of iRNI was 15.00% (9/60) for anterolateral approach, 16.7% (2/12) for lateral approach and 18.2% (6/33) for posterior approach (p  > 0.05).

Intramedullary nailing is the preferred method of internal fixation for humeral shaft fractures that has the lowest rate of iRNI. Compared with anterolateral and posterior approaches, the lateral surgical approach had a higher incidence of iRNI. The rate of iRNI in MIPO was lower than that in open reduction and internal fixation.

Level IV.

For nerve injuries, not amendable to tensionless epineural coaptation of the nerve, autografts are the preferred treatment. Although absorbable sutures are not recommended for nerve repair, there is no evidence that non-absorbable sutures are superior to absorbable sutures. This study aims to assess the effectiveness of non-absorbable monofilament nylon sutures, absorbable monofilament vicryl sutures, and fibrin glue when used for nerve grafting.

Lewis rats (N = 32) were subjected to a sciatic nerve transection and randomly assigned to a group: graft with Nylon, graft with Vicryl, graft with Fibrin Glue, or no graft. Motor function, sensory function, and thermal pain were assessed during a 12-week recovery period, and immunohistochemistry was used to assess macrophage response.

At 12 weeks, the Vicryl and Nylon groups had significantly larger ankle angles at to lift off, which is a measure of motor function, compared to injured controls (p < 0.05). Grafted rats displayed no difference in thermal response but hypersensitivity to mechanical stimuli compared to the uninjured hindlimb. The Nylon, Vicryl, and Fibrin Glue groups all had significantly less atrophy of the gastrocnemius muscle compared to injured controls (p < 0.0001). In the Fibrin Glue group, 3/9 grafts did not incorporate. The Nylon group had significantly less (p = 0.0004) axon growth surrounding the suture holes compared to the Vicryl group. There were no differences in the axon counts, motor neurons, or sensory neurons between all grafted rats.

These results demonstrate that vicryl sutures work just as well as nylon for nerve recovery after injury and grafting.

Despite recent advancements in peripheral nerve regeneration, the creation of nerve conduits with chemical and physical cues to enhance glial cell function and support axonal growth remains challenging. This study aimed to assess the impact of electrical stimulation (ES) using a conductive nerve conduit on sciatic nerve regeneration in a rat model with transection injury. The study involved the fabrication of conductive nerve conduits using silk fibroin and Au nanoparticles (AuNPs). Collagen hydrogel loaded with green fluorescent protein (GFP)-positive adipose-derived mesenchymal stem cells (ADSCs) served as the filling for the conduit. Both conductive and non-conductive conduits were applied with and without ES in rat models. Locomotor recovery was assessed using walking track analysis. Histological evaluations were performed using H&E, luxol fast blue staining and immunohistochemistry. Moreover, TEM analysis was conducted to distinguish various ultrastructural aspects of sciatic tissue. In the ES + conductive conduit group, higher S100 (p < 0.0001) and neurofilament (p < 0.001) expression was seen after 6 weeks. Ultrastructural evaluations showed that conductive scaffolds with ES minimized Wallerian degeneration. Furthermore, the conductive conduit with ES group demonstrated significantly increased myelin sheet thickness and decreased G. ratio compared to the autograft. Immunofluorescent images confirmed the presence of GFP-positive ADSCs by the 6th week. Locomotor recovery assessments revealed improved function in the conductive conduit with ES group compared to the control group and groups without ES. These results show that a Silk/AuNPs conduit filled with ADSC-seeded collagen hydrogel can function as a nerve conduit, aiding in the restoration of substantial gaps in the sciatic nerve with ES. Histological and locomotor evaluations indicated that ES had a greater impact on functional recovery compared to using a conductive conduit alone, although the use of conductive conduits did enhance the effects of ES.