Peripheral nerve injuries (PNIs) present a persistent clinical challenge because of the intrinsically limited regenerative capacity of peripheral nerves. While dental pulp stem cells (DPSCs) exhibit significant neuroregenerative potential, their therapeutic efficacy is constrained by hostile microenvironments and inherent functional heterogeneity. Genetic modification may offer a promising strategy to enhance their therapeutic capabilities. DPSCs were induced toward neural lineage differentiation, and key gene candidates were identified through qRT-PCR. Lentiviral-mediated gene interference was performed to modulate target gene expression, followed by comprehensive analysis of differentiation outcomes using qRT-PCR, Western blotting, and immunofluorescence assays. RNA sequencing was employed to uncover associated signaling pathways, which were subsequently validated through pharmacological inhibition with specific inhibitors. The therapeutic efficacy of genetically engineered DPSCs was evaluated in a rat model of sciatic nerve crush injury, with neural regeneration quantitatively assessed via neuroelectrophysiological measurements and histological analyses. LARP7 positively regulated the Schwann cell-like differentiation of DPSCs, as well as their trophic and anti-inflammatory effects, thus enhancing its therapeutic effects on nerve repair and promoting functional recovery. Mechanistically, we found that LARP7 remodeled cytokine-cytokine receptor interactions, enhancing trophic support while attenuating proinflammatory responses, and activated the PI3K-Akt-mTOR signaling pathway, with ERBB4 serving as a critical downstream effector, promoting DPSC differentiation into Schwann cell-like phenotypes. Collectively, LARP7-mediated changes in DPSCs establish a new therapeutic paradigm that addresses the limitations of current stem cell-based interventions and enables the development of standardized biotherapeutics for peripheral nerve repair.

Background Sensory recovery following digital nerve neurorrhaphy is often incomplete, and strategies to enhance regeneration remain under investigation. Low-frequency transcutaneous electrical stimulation has been proposed as a potential adjunctive therapy, but its efficacy in clinical settings is uncertain. Methods In this randomized controlled trial, 32 patients with isolated traumatic digital nerve injuries underwent surgical neurorrhaphy at a tertiary care hospital. Participants were randomly allocated to an intervention group (n = 16) or sham group (n = 16). The intervention consisted of a single postoperative session of square-pulsed, biphasic transcutaneous electrical stimulation at 20 Hz for 1 hour. The sham group received identical conditions without active stimulation. After stimulation, patients underwent physiotherapy sessions for three months. Sensory recovery was assessed using Semmes-Weinstein monofilament testing and two-point discrimination at baseline, 1 week, 1 month, and 3 months postoperatively. Results Both groups showed progressive sensory improvement throughout follow-up, approaching normal values at 3 months. No statistically significant differences were observed between groups in any outcome measure. Confidence intervals for group comparisons overlapped, and no clinically meaningful differences were detected. No adverse effects were reported. Conclusions In this model, a single postoperative session of low-frequency transcutaneous electrical stimulation did not significantly enhance sensory recovery after digital nerve repair. Further research with varied stimulation protocols, repeated sessions, or extended follow-up may be warranted to clarify its potential role in peripheral nerve regeneration. Level of Evidence Therapeutic Level I.

Abstract The trapezius muscle is a large, superficial muscle of the posterior thoracic region that plays a fundamental role in scapular stabilization, upper limb movement, and cervical spine biomechanics. Numerous anatomical studies have demonstrated that the trapezius exhibits considerable morphological variability in its origin, insertion, fiber arrangement, innervation patterns, and muscular segmentation. Different researchers have reported variations including accessory muscle slips, partial absence of specific portions (particularly the lower or middle fibers), asymmetry between sides, atypical attachments to the clavicle or scapula, and deviations in the course of the spinal accessory nerve. Some cadaveric and imaging-based studies have also described variations in muscle thickness, fascicle orientation, and aponeurotic structure, which may influence force transmission and scapulothoracic mechanics. From a biomechanical perspective, these anatomical differences may alter scapular kinematics, shoulder elevation patterns, and load distribution across the cervical and thoracic spine. Functional implications include potential predisposition to shoulder impingement, scapular dyskinesis, neck pain syndromes, and altered postural control. Furthermore, anatomical variability has important clinical relevance in surgical procedures, reconstructive techniques, nerve repair, and rehabilitation planning. Overall, the available literature suggests that anatomical variations of the trapezius muscle are more common than traditionally assumed and may significantly influence both normal movement patterns and pathological conditions. Recognition of these variations is essential for anatomists, clinicians, surgeons, and physiotherapists to ensure accurate diagnosis, effective treatment, and optimized functional outcomes.

Background Adenoid cystic carcinoma (ACC) of the salivary glands is a rare but aggressive malignancy known for perineural invasion (PNI), allowing tumor spread along cranial nerves to the skull base, Meckel’s cave, and cavernous sinus. Cavernous sinus involvement has traditionally been considered inoperable due to the density of neurovascular structures. Recent advancements in skull base microsurgery and anatomical landmark–guided navigation have enabled radical tumor resection in carefully selected patients. Objective To describe a tailored pretemporal extradural transcavernous skull base approach, combined with infratemporal fossa exposure, for radical resection of parotid ACC with extensive PNI into Meckel’s cave and the cavernous sinus, emphasizing internal carotid artery (ICA) skeletonization, fascicular-level nerve dissection and repair, and precision bone work. Methods A 54-year-old male presented with progressive left facial paralysis (House–Brackmann grade VI), trigeminal pain (V 1 ), diplopia, and cranial nerve IV and VI palsies. MRI demonstrated a tumor extending along the mandibular nerve (V 3 ) via the foramen ovale into Meckel’s cave and cavernous sinus, circumferentially encasing the cavernous ICA with patent lumen. High resolution neuroimaging confirmed perineural spread; PET-CT showed no metastasis. A modified Dolenc pretemporal extradural transcavernous approach was performed without orbitozygomatic osteotomy. Bone removal was limited to V 2 –V 3 triangle drilling, exposing the infratemporal fossa and Meckel’s cave. ICA skeletonization was guided by the vidian canal, lingual petroclival ligament, and petrosphenoidal ligament, with intraoperative Doppler confirmation. Fascicular-level neurorrhaphy reconstructed infiltrated V 3 fibers. Multilayer skull base reconstruction with autologous fat grafts provided watertight closure and radioprotection. Results Gross total resection was achieved with preserved integrity of the ICA and all cranial nerves. No new neurological deficits occurred; preexisting palsies remained stable. Pathology confirmed ACC with extensive PNI; immunohistochemistry was positive for Hematoxylin and eosin, B-catenin, CK-7, and S100. Postoperative MRI verified complete cavernous sinus tumor removal. The patient recovered well and was referred for adjuvant stereotactic radiotherapy. Conclusion This case demonstrates that even extensive cavernous sinus invasion by parotid ACC can be safely addressed with curative intent through precision-based microsurgery. A modified Dolenc approach with limited bone work and infratemporal extension enables maximal resection while preserving function. Strategic reconstruction optimizes safety for adjuvant radiation. This report adds to the growing evidence supporting aggressive yet function-preserving surgical management of malignant skull base tumors in multidisciplinary oncology programs.

Organ-on-a-chip (OoC) platforms are microfluidic systems that replicate key aspects of human tissue physiology in controlled environments. Originally developed for drug testing and disease modeling, they provide a more human-specific and reproducible alternative to traditional preclinical models, which often fail to capture the complexity of tissues relevant to plastic and reconstructive surgery. This review synthesizes current OoC technologies with direct application to plastic and reconstructive surgery, focusing on skin-, vessel-, adipose-, and nerve-on-a-chip systems. The analysis emphasizes how these platforms model tissue structure, function, and interactions, and evaluates their ability to simulate clinically relevant processes. Skin-on-a-chip platforms enable dynamic modeling of wound healing, graft integration, and barrier function. Vessel-on-a-chip systems replicate microcirculatory flow, endothelial function, and vascular wall behaviors, supporting studies of flap viability and ischemia-reperfusion injury. Adipose-on-a-chip preserves lipid metabolism and inflammatory signaling, informing research into fat graft retention and remodeling. Nerve-on-a-chip platforms allow real-time monitoring of nerve injury and regeneration, aiding evaluation of nerve repair and graft performance. Across these systems, OoC models provide more clinically relevant insights than animal or static in vitro approaches, though limitations persist, including restricted physiological complexity, lack of platform standardization, short-term viability, and scalability challenges. OoC platforms offer significant promise for advancing plastic and reconstructive surgery research by bridging translational gaps and aligning in vitro modeling with surgical outcomes such as graft take and nerve function. Future directions include incorporating immune elements, developing multi-tissue systems, expanding commercial accessibility, and improving long-term functionality. As these technologies mature, they have the potential to accelerate innovation and improve patient outcomes in reconstructive surgery.

Post-acute phase Rac1 activation promotes long-term recovery of ischemic stroke via the Pak1/p38/β-catenin pathway.

Calcium peroxide-loaded ovalbumin scaffolds with sustained oxygen release capacity for regulating the growth behavior of nerve cells and endothelial cell.

Optimizing scaffold properties for nerve regeneration: Effects of bioactive glass in 3D-printed chitosan structures.

Integrated implantable triboelectric charge collector for nerve repair

Background: Peripheral nerve injury can happen for a variety of causes. Despite major breakthroughs in microsurgery, nerve repair results are not always sufficient. Methods: Thirty-two Wistar albino rats were split into four groups: primary nerve repair (PNR), PNR with vitamin D3 treatment, nerve crush injury (NCI), and NCI with vitamin D3 treatment. In the PNR + D3 and NCI + D3 groups, 1 mcg/kg of vitamin D3 was given intraperitoneally on days 1, 3, 5, and 7 of the 12-week healing period. Electrophysiological measurements were taken prior to the injury. At 12 weeks after damage, a hot plate test was performed to assess acute pain, and the electrophysiological measurements were repeated. Before the rats were sacrificed, biopsy samples from the right sciatic nerve were collected for histopathological evaluation. Results: Post-healing action potential values were not statistically different between the PNR and PNR + D3 groups; however, they were considerably lower in the NCI + D3 group than in the NCI group. The reaction time in the hot plate test was considerably slower in the D3-treated groups compared to the control groups. Histopathology score was substantially higher in the PNR + D3 group as compared to the PNR group, and lower in the NCI + D3 group as compared to the NCI group. Conclusions: Other than improved myelination, vitamin D3 treatment following primary repair of transected nerves produced no statistically significant improvement. Vitamin D3 treatment caused a negative impact on the crush injury, as assessed by the findings of histopathology and electrophysiological measurements. Overall, the results indicate that the efficacy of vitamin D3 treatment may vary depending on the type of injury.

When nerves are severed, such as during traumatic injury, an acute injury state is induced, characterized by biological and physical changes in the proximal and distal stumps. Beyond the initial injury phase, over a time frame of weeks to months, nerves that remain unrepaired progressively enter a chronic injury state, characterized by a change in the extracellular matrix structure of the distal stump, the down-regulation of neurotrophic factors and the loss of macrophages' and Schwann cells' ability to clear out degraded axons and myelin. There are also potential systemic impacts away from the site of injury, including in end organs such as muscle and bone. The literature suggests that several of these processes may be strongly influenced by innate and adaptive immune system responses, including a major role for complement pathways. This review details evidence in favor of such a possibility, as well as knowledge gaps and areas for future investigation.

Reconstruction of the inferior alveolar nerve (IAN) following segmental mandibulectomy presents microsurgical challenges. Traditional neurorrhaphy using microsutures can be technically demanding, time-consuming, and may induce local trauma to the nerve graft. The authors report the case of a 52-year-old male with osteoradionecrosis of the mandible who underwent segmental mandibulectomy and immediate reconstruction of the IAN using an allogeneic nerve graft. For restoration of IAN continuity, a processed nerve allograft (Avance Nerve Graft, Axogen, Alachua, FL) was secured using Nerve Tape (BioCircuit Technologies Inc, Atlanta, GA), a sutureless coaptation device constructed with biological scaffold material and nitinol microhook technology to secure and align nerve ends. This product is composed of acellularized porcine small intestinal submucosal (SIS) tissue, like the Axoguard wrap, providing comparable handling and integration properties. This approach allowed rapid, atraumatic indirect neurorrhaphy of the IAN. Postoperative follow-up will be performed to determine whether progressive neurosensory recovery has occurred. Nerve Tape offers a promising alternative for nerve coaptation in trigeminal nerve reconstruction.

IntroductionHigh peripheral nerve injuries disrupt the balance between flexor and extensor muscle groups and result in significant impairment of strength, coordination and dexterity. Primary nerve repair is widely accepted as the optimal treatment following transection injury, but outcomes after high-level nerve reconstruction remain unpredictable. Prolonged denervation commonly leads to irreversible muscle atrophy, limiting the potential for meaningful distal functional recovery despite technically successful nerve repair.Reconstructive strategies:Different surgical strategies are available to restore motor function after high peripheral nerve injuries. Tendon transfers have long been regarded as the reference standard for reconstructing lost muscle function, offering predictable and relatively early restoration of key movements. However, tendon transfers may compromise muscle balance, excursion, and fine motor control. Nerve transfers have emerged as an alternative strategy, aiming to prevent motor loss by reinnervating native muscles. While nerve transfers may better preserve physiological patterns of movement, they require prolonged periods for reinnervation and depend on patient factors, timing, and access to rehabilitation.Review focusMore recent reconstructive strategies seek to combine the advantages of both techniques, offering 'the best of both worlds' through hybrid approaches that integrate tendon and nerve transfers. This expert opinion review discusses the current opportunities and challenges associated with these hybrid strategies in the management of high upper extremity peripheral nerve injuries. The biomechanical principles, indications and limitations of tendon transfers, nerve transfers and combined approaches are compared, with particular attention to timing, patient selection, and functional goals.

Peripheral nerve injuries (PNIs) are a significant cause of global disability, often leading to lifelong sensory and motor deficits. Increasing efforts to unveil the psychosocial implications of such injuries is being made. The aim of this study was to determine the impact of preoperatively diagnosed mental health disorder (MHD), specifically major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD), on short-term outcomes following PNI repair. A large, retrospective cohort, using the TriNetX Collaborative Global Network database queried on April 9, 2025, was used to identify patients undergoing PNI repair with preoperative MHD diagnoses. Propensity matching was performed, allowing analysis of 30-day and 90-day postoperative outcomes in patients with MHD along with subgroup analysis of those diagnosed with MDD, GAD, or PTSD. Mental health disorder (n = 2521), MDD (n = 1107), GAD (n = 996), and PTSD (n = 938) groups were found to have increased emergency department use and hospital readmission postoperatively. Patients with MHD were less likely to attend outpatient follow-up in clinic or use occupational therapy services. Complications and opioid consumptions were similar among all groups. Following PNI repair, patients with pre-existing MHD demonstrated increased hospital resource utilization and decreased outpatient follow-up despite similar complication and opioid use rates. The need for a comprehensive, multifaceted approach to optimize treatment outcomes following PNI, specifically those with concomitant MHD, is obviated by the findings in this study.

Peripheral nerve regeneration is most rapid during the early post-injury period but gradually slows over time, often limiting functional recovery. Electrical stimulation (ES) delivered via percutaneous needle electrodes has been shown to modulate the local neural microenvironment and promote axonal regeneration; however, the optimal temporal window and duration of stimulation remain unclear. This study aimed to evaluate the time-dependent effects of needle-based ES on peripheral nerve regeneration in a rat model of sciatic nerve transection, using a well-established silicone nerve conduit as a stable and reproducible non-biodegradable repair model. Female Sprague-Dawley rats underwent sciatic nerve transection and repair. Postoperatively (PO), animals were randomly assigned to control (C) needle insertion or needle-based ES groups, receiving stimulation for either 3 weeks (C-3W-PO and ES-3W-PO, respectively) or 7 weeks (C-7W-PO and ES-7W-PO, respectively). Functional recovery was evaluated using cold plate latency and rotarod performance tests. Electrophysiological assessments included measurements of nerve conduction velocity (NCV), compound muscle action potential amplitude, and muscle action potential (MAP) area. Histomorphometric analysis of regenerated nerve tissue quantified total nerve cross-sectional area, endoneurial space, axon number, and axon density. Retrograde labeling with fluoro-gold (FG) was used to quantify reinnervated motor neurons. Immunohistochemical analyses of calcitonin gene-related peptide (CGRP) and macrophage-associated markers were conducted to assess sensory neuropeptide expression and immune cell infiltration within the regenerated nerve. ES significantly improved both sensory and motor recovery in a duration-dependent manner. Behavioral data showed increased cold pain thresholds and improved motor coordination in ES groups, with the most pronounced functional gains observed in the ES-7W-PO group. Electrophysiological measures revealed higher NCV, amplitude, and MAP area in ES-treated animals, with the most pronounced improvements at 7 weeks. Morphologically, ES enhanced nerve regeneration, as evidenced by increased total and endoneurial areas, axonal counts, and axon density. FG-labeled neuron counts were significantly elevated in ES groups, indicating enhanced motor reinnervation. At 3 weeks, ES induced higher CGRP expression and macrophage density, suggesting transient activation of sensory-associated and pro-regenerative immune responses during the early post-injury phase. These findings demonstrate that ES accelerates peripheral nerve repair in rats and that sustained stimulation across the early regenerative window yields superior structural and functional outcomes.

Background: Axonal misdirection remains a major limitation in peripheral nerve repair. While nerve guidance conduits (NGCs) and nerve scaffolds (NSCs) have advanced structurally, it is unclear whether these designs effectively reduce misdirection compared to autografts (ANGs). This systematic review evaluates the impact of NGC and NSC structural features on axonal dispersion and reinnervation accuracy using retrograde tracing animal models. Methods: A systematic search was performed through Medline (PubMed), Scopus (EBSCOhost), and the Cochrane Library from inception to December 2024. Eligible studies included mammalian in vivo models of peripheral nerve transection repaired by direct coaptation, autografts, or artificial conduits and assessed with retrograde axonal tracing. Data on neurons labeling, innervation accuracy, and histomorphometric parameters were extracted, and misdirection rates were calculated. Risk of bias was assessed using the SYRCLE tool. Due to heterogeneity, data were synthesized narratively following the SWiM framework. Results: Out of 4043 records identified through database searching and 37 through citation searching, 19 studies (49 experimental groups) met the inclusion criteria. Motoneuron counts were consistently reported across all arms, but no outcome assessing axonal misdirection was reported in more than half. Structured designs resulted in outcomes more closely aligned with ANG repair, while unstructured generally underperformed, and certainty of evidence was very low. Discussion: The evidence in this study was limited by high risk of bias, substantial inconsistency across heterogeneous study designs and outcomes, and imprecision from small animal models with sparse outcome measures. Despite the trend for structured designs to improve over basic hollow designs, current evidence does not support any structure as superior. Future research should be more standardized to provide reliable knowledge translational into clinical practice.

Peripheral nerve injuries pose significant challenges due to limited regenerative capacity and functional recovery, especially in large or complex defects. Traditional repair methods using non-vascularized autologous nerve grafts often result in suboptimal outcomes due to ischemia-induced central necrosis and delayed axonal regeneration. Vascularized nerve grafts (VNGs), which provide an intrinsic blood supply, have emerged as a promising alternative to enhance nerve repair by improving graft survival, supporting Schwann cell viability, and promoting early neovascularization. This review on vascularized nerve grafting examines its advantages, challenges, and emerging experimental approaches. VNGs demonstrate superior functional outcomes compared to non-vascularized grafts, with improved motor and sensory recovery, and higher axonal density, particularly in long-gap and delayed repairs. Although the use of vascularized nerve grafts is limited by technical complexity, increased operative time, and donor site morbidity. In this study we aim to provide a comprehensive overview of the rationale, outcomes, and challenges associated with vascularized nerve grafts, while highlighting emerging experimental strategies poised to overcome current limitations in peripheral nerve repair.

Spinal cord injury (SCI) repair has been a great challenge worldwide because of its complex regeneration mechanisms and limited self-healing. The biomimetic construction of a bioactive scaffold represents a promising direction for SCI repair. Inspired by the efficient self-healing properties of the neonatal spinal cord, this study developed a neonatal spinal-cord-like scaffold (NSLS) aimed at regulating SCI repair at different stages. The NSLS features a neonatal spinal cord matrix, multilevel biomimetic structures, and matching mechanical strength via personalized laser processing and dual-network cross-linking. The microenvironments of the NSLS activate energy metabolism, synaptic formation, and the gliogenesis of neural stem cells (NSCs). Notably, the NSLS could achieve rapid hemostasis and integration with the host spinal cord, facilitating nutrient infiltration and establishing a stable connection in the early stage. Furthermore, NSCs loaded with NSLS (NSLT) promoted nerve repair by promoting microglial M2 polarization to decrease local inflammatory responses in the intermediate stage. Finally, axons grow directionally within the channels and form new connections to enhance neural repair and functional recovery in the late stage. Therefore, NSLT could significantly enhance nerve regeneration and functional recovery after SCI via stage-specific regulation.

ABSTRACT The impact of ZnO, fullerene C 60 and polyaniline (PANI) nanoparticles (NPs) on hybrid nerve conduits was studied to evaluate their role in peripheral nerve repair. Alginate–gelatin (Alg/Gel) conduits were synthesized via 5‐fold freeze‐thaw cycles under ultrasound and loaded with the NPs. Their effects on swelling, porosity, hydrophilicity, electrical conductivity, mechanical strength and vitamin B12 permeability were analysed. Composites with 0.15 mg/mL PANI showed increased conductivity: Alg/Gel/PANI (0.208 S/m), ZnO/Alg/Gel/PANI (0.744 S/m) and C 60 /Alg/Gel/PANI (0.342 S/m), exceeding controls by 1.45–3.57 times. ZnO/Alg/Gel/PANI had the highest vitamin B12 permeability—55% over 7 days—due to its high porosity. Pure PANI showed low antioxidant activity (AOA, 17.6%), which rose to 46%–90% when combined with Alg and Gel. L929 cells remained viable in contact with all modified samples, indicating biocompatibility. Among the composites, C 60 /Alg/Gel/PANI displayed superior mechanical stability and enhanced nerve regeneration potential, highlighting its promise for long‐term use in functional nerve repair. Highlights Electrical conductivity increases up to 2 times in the presence of PANI, ZnO, fullerene C60 ZnO and C60 improve composites' mechanical stability and surface hydrophilicity The best permeability of vitamin B12 occurs through the ZnO/Alg/Gel/PANI wall In vivo in rat model study confirms the absence of toxicity and biocompatibility of composites

Stem Cell-based Nerve Regenerative Therapies: The Role of Adipose-Derived Stem Cells (ADSCs) in Preventing Nerve Adhesions and Promoting Axonal Nerve Repair.