Delayed Ferumoxtran-10-Enhanced Magnetic Resonance Neurography of the Lumbosacral Plexus: Impact on Vascular Suppression and Image Quality.

BACKGROUND: Intravenous Ferumoxtran-10 belongs to ultra-small superparamagnetic iron oxide particles and can be used for magnetic resonance neurography (MRN) as an alternative to other imaging methods which use contrast agents. PURPOSE: To examine the impact of intravenous Ferumoxtran-10 on vascular suppression and compare image quality to gadolinium (Gd)-enhanced image acquisition in MRN of lumbosacral plexus (LS). STUDY TYPE: Prospective. POPULATION/SUBJECTS: 17 patients with Ferumoxtran-10-enhanced MRN, and 20 patients with Gd-enhanced MRN. FIELDSTRENGTH/SEQUENCE: 3T/3D STIR sequence. ASSESSMENT: Image quality, nerve visibility and vascular suppression were evaluated by 3 readers using a 5-point Likert scale. STATISTICAL TESTS: Inter-reader agreement (IRA) was calculated using intraclass coefficients (ICC). Quantitative analysis of image quality was performed by signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements and compared using Student's t-testing. RESULTS: Image quality, nerve visibility and vascular suppression were significantly higher for Ferumoxtran-10-enhanced MRN compared to Gd-enhanced MRN sequences (p < 0.05). IRA for image quality of nerves was good in Gd-enhanced and Ferumoxtran-10 MRN with ICC values of 0.76 and 0.89, respectively. IRA for nerve visibility was good in Gd- and Ferumoxtran-10 enhanced MR neurography (ICC 0.72 and 0.90). Mean SNR was significantly higher in Ferumoxtran-10-enhanced MRN for all analyzed structures, while mean CNR was for significantly better for S1 ganglion and femoral nerve in Ferumoxtran-10-enhanced MRN (p < 0.05). DATA CONCLUSION: Ferumoxtran-10-enhanced MRN of the LS plexus showed significantly higher image quality and nerve visibility with better vascular suppression as compared to Gd-enhanced MRN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Bone marrow mesenchymal stem cells in treatment of peripheral nerve injury.

Peripheral nerve injury (PNI) is a common neurological disorder and complete functional recovery is difficult to achieve. In recent years, bone marrow mesenchymal stem cells (BMSCs) have emerged as ideal seed cells for PNI treatment due to their strong differentiation potential and autologous transplantation ability. This review aims to summarize the molecular mechanisms by which BMSCs mediate nerve repair in PNI. The key mechanisms discussed include the differentiation of BMSCs into multiple types of nerve cells to promote repair of nerve injury. BMSCs also create a microenvironment suitable for neuronal survival and regeneration through the secretion of neurotrophic factors, extracellular matrix molecules, and adhesion molecules. Additionally, BMSCs release pro-angiogenic factors to promote the formation of new blood vessels. They modulate cytokine expression and regulate macrophage polarization, leading to immunomodulation. Furthermore, BMSCs synthesize and release proteins related to myelin sheath formation and axonal regeneration, thereby promoting neuronal repair and regeneration. Moreover, this review explores methods of applying BMSCs in PNI treatment, including direct cell transplantation into the injured neural tissue, implantation of BMSCs into nerve conduits providing support, and the application of genetically modified BMSCs, among others. These findings confirm the potential of BMSCs in treating PNI. However, with the development of this field, it is crucial to address issues related to BMSC therapy, including establishing standards for extracting, identifying, and cultivating BMSCs, as well as selecting application methods for BMSCs in PNI such as direct transplantation, tissue engineering, and genetic engineering. Addressing these issues will help translate current preclinical research results into clinical practice, providing new and effective treatment strategies for patients with PNI.

Hybrid construction of tissue-engineered nerve graft using skin derived precursors induced neurons and Schwann cells to enhance peripheral neuroregeneration.

Peripheral nerve injury is a major challenge in clinical treatment due to the limited intrinsic capacity for nerve regeneration. Tissue engineering approaches offer promising solutions by providing biomimetic scaffolds and cell sources to promote nerve regeneration. In the present work, we investigated the potential role of skin-derived progenitors (SKPs), which are induced into neurons and Schwann cells (SCs), and their extracellular matrix in tissue-engineered nerve grafts (TENGs) to enhance peripheral neuroregeneration. SKPs were induced to differentiate into neurons and SCs in vitro and incorporated into nerve grafts composed of a biocompatible scaffold including chitosan neural conduit and silk fibroin filaments. In vivo experiments using a rat model of peripheral nerve injury showed that TENGs significantly enhanced nerve regeneration compared to the scaffold control group, catching up with the autograft group. Histological analysis showed improved axonal regrowth, myelination and functional recovery in animals treated with these TENGs. In addition, immunohistochemical staining confirmed the presence of induced neurons and SCs within the regenerated nerve tissue. Our results suggest that SKP-induced neurons and SCs in tissue-engineered nerve grafts have great potential for promoting peripheral nerve regeneration and represent a promising approach for clinical translation in the treatment of peripheral nerve injury. Further optimization and characterization of these engineered constructs is warranted to improve their clinical applicability and efficacy.

Activation of P2X7R Inhibits Proliferation and Promotes the Migration and Differentiation of Schwann Cells.

In the vertebrate nervous system, myelination of nerve fibers is crucial for the rapid propagation of action potentials through saltatory conduction. Schwann cells-the main glial cells and myelinating cells of the peripheral nervous system-play a crucial role in myelination. Following injury during the repair of peripheral nerve injuries, a significant amount of ATP is secreted. This ATP release acts to trigger the dedifferentiation of myelinating Schwann cells into repair cells, an essential step for axon regeneration. Subsequently, to restore nerve function, these repair cells undergo redifferentiate into myelinating Schwann cells. Except for P2X4R, purine receptors such as P2X7R also play a significant role in this process. In the current study, decreased expression of P2X7R was observed after sciatic nerve injury, followed by a gradual increase to the normal level of P2X7R expression. In vivo experiments showed that the activation of P2X7R using an agonist injection promoted remyelination, while the antagonists hindered remyelination. Further, in vitro experiments supported these findings and demonstrated that P2X7R activation inhibited the proliferation of Schwann cells, but it promoted the migration and differentiation of the Schwann cells. Remyelination is a prominent feature of the nerve regeneration. In the current study, it was proposed that the manipulation of P2X7R expression in Schwann cells after nerve injury could be effective in facilitating nerve remyelination.

Collagen protein-chitosan nerve conduits with neuroepithelial stem cells promote peripheral nerve regeneration.

The peripheral nervous system consists of ganglia, nerve trunks, plexuses, and nerve endings, that transmit afferent and efferent information. Regeneration after a peripheral nerve damage is sluggish and imperfect. Peripheral nerve injury frequently causes partial or complete loss of motor and sensory function, physical impairment, and neuropathic pain, all of which have a negative impact on patients' quality of life. Because the mechanism of peripheral nerve injury and healing is still unclear, the therapeutic efficacy is limited. As peripheral nerve injury research has processed, an increasing number of studies have revealed that biological scaffolds work in tandem with progenitor cells to repair peripheral nerve injury. Here, we fabricated collagen chitosan nerve conduit bioscaffolds together with collagen and then filled neuroepithelial stem cells (NESCs). Scanning electron microscopy showed that the NESCs grew well on the scaffold surface. Compared to the control group, the NESCs group contained more cells with bigger diameters and myelinated structures around the axons. Our findings indicated that a combination of chitosan-collagen bioscaffold and neural stem cell transplantation can facilitate the functional restoration of peripheral nerve tissue, with promising future applications and research implications.

Knowledge, attitudes, and practices of healthcare professionals toward rehabilitation of peripheral nerve injury.

Peripheral nerve injury (PNI) occurs due to damage of peripheral nerves, with healthcare professionals playing significant roles in PNI rehabilitation. This study aimed to explore the knowledge, attitudes, and practices (KAP) towards PNI rehabilitation among healthcare professionals. This cross-sectional study was conducted on June 2023 in China and healthcare professionals were enrolled. A total of 611 valid questionnaires were collected, with 62.52% female respondents. Mean scores for KAP were 14.26 ± 2.044 (possible range: 0-19), 29.77 ± 3.622 (possible range: 7-35), and 41.55 ± 9.523 (possible range: 11-55), respectively. Multivariate logistic regression revealed positive associations of professional titles (OR = 1.743, 95% CI: 1.083-2.804), occupation (OR = 1.833, 95% CI: 1.151-2.919), and involvement in treatment or care of PNI patients (OR = 1.462, 95% CI: 1.024-2.088) with knowledge. Knowledge (OR = 1.155, 95% CI: 1.042-1.280), gender (OR = 2.140, 95% CI: 1.255-3.646), education (OR = 2.258, 95% CI: 1.131-4.507), and involvement in treatment or care of PNI patients (OR = 2.463, 95% CI: 1.460-4.155) were positively associated with attitude. Attitude (OR = 1.214, 95% CI: 1.148-1.283), bachelor's degree education (OR = 0.548, 95% CI: 0.326-0.919), master's degree or higher (OR = 0.545, 95% CI: 0.308-0.964), having rehabilitation training for PNI (OR = 2.485, 95% CI: 1.633-3.781), and involvement in treatment or care of PNI patients (OR = 2.093, 95% CI: 1.395-3.138) were independently associated with practice. Healthcare professionals exhibited moderate knowledge, positive attitudes, and moderate practices towards the PNI rehabilitation. Those involved in the treatment or care of PNI have significantly higher KAP. Targeted interventions were needed to enhance understanding and promote proactive engagement in clinical practice.

Suprascapular nerve peripheral nerve stimulation for malignancy-related pain: A case series.

Background: Blockade of the suprascapular nerve is an effective diagnostic tool in the workup and potential treatment of shoulder pain. For chronic shoulder pain, peripheral nerve stimulation has been shown to provide significant, sustained pain relief. However, no literature to date has described peripheral nerve stimulation for the treatment of oncologic shoulder pain. Objectives: We describe two cases of chronic oncologic-related shoulder pain that responded to posterior suprascapular peripheral nerve stimulator placement to facilitate future progress and discussion in the fields of peripheral nerve stimulation and oncology pain. Methods: Two subjects with chronic shoulder pain underwent ultrasound-guided peripheral nerve stimulation therapy at the suprascapular nerve. Results: At follow-up visits (30 and 98 days after procedure), both subjects reported greater than 50% pain relief as measured by the numerical rating scale (NRS). Conclusions: Peripheral nerve stimulator placement at the suprascapular nerve is a feasible procedure to treat oncologic shoulder pain via the described technique. Both subjects experienced clinically significant pain relief and decreased oral analgesic medication intake, and decreased medication-related side effects. This warrants further investigation including large comparative, prospective studies to better assess efficacy and safety of this approach.

Wrist Immobilization after Surgical Decompression of the Median Nerve in Carpal Tunnel Syndrome: A Systematic Review.

Objective The most common compressive neuropathy of the upper limbs is carpal tunnel syndrome (CTS). Historically, there has been a tendency to apply immobilization in the postoperative period, a practice that has decreased in recent years. This review aims to assess whether there is scientific evidence to justify the use of immobilization in the postoperative care of CTS decompression. Methods The following databases were used: Biblioteca Virtual em Saúde (BVS), PubMed National Library of Medicine - (NLM), Cochrane Library, Scientific Electronic Library Online (SciELO), and EMBASE. The following inclusion criteria were used: 1) discussion of the postoperative period of median nerve decompression surgery in CTS; 2) comparison of results after surgical decompression in CTS between wrist immobilization or local dressing; 3) all languages, regardless of the year of publication; and 4) all types of publications. The following exclusion criteria were used: 1) studies that did not evaluate the postoperative period of CTS decompression; 2) lack of evaluation of the outcome related to the application of local dressing or some form of wrist immobilization after the surgical decompression procedure; and 3) repeated publications. Results The literature search resulted in 336 relevant publications. In the end, 18 publications were chosen. Systematic reviews, randomized clinical trials, and cross-sectional studies were found. Conclusions Due to the scarcity of evidence supporting the use of immobilization coupled with the higher costs associated with the practice, it has become less and less frequent in recent decades. Clinical relevance In the literature, two approaches to postoperative care for CTS decompression are described: immobilization or just local dressing. According to the available scientific evidence, it is worth evaluating which one is better.

Therapeutic roles of coenzyme Q10 in peripheral nerve injury-induced neurosensory disturbances: Mechanistic insights from injury to recovery.

Peripheral nerve injuries (PNIs) are prevalent conditions mainly resulting from systemic causes, including autoimmune diseases and diabetes mellitus, or local causes, for example, chemical injury and perioperative nerve injury, which can cause a varying level of neurosensory disturbances (NSDs). Coenzyme Q10 (CoQ10) is an essential regulator of mitochondrial respiration and oxidative metabolism. Here, we review the pathophysiology of NSDs caused by PNIs, the current understanding of CoQ10's bioactivities, and its potential therapeutic roles in nerve regeneration, based on evidence from experimental and clinical studies involving CoQ10 supplementation. In summary, CoQ10 supplementation shows promise as a neuroprotective agent, potentially enhancing treatment efficacy for NSDs by reducing oxidative stress and inflammation. Future studies should focus on well-designed clinical trials with large sample sizes, using CoQ10 formulations with proven bioavailability and varying treatment duration, to further elucidate its neuroprotective effects and to optimize nerve regeneration in PNIs-induced NSDs.

Malignant Transformation of Plexiform Neurofibroma Due to Neglected Giant Soft Tissue Swelling of the Back: A Case Report.

Neurofibromatosis type 1 can be severe and associated with malignant transformation. Proper follow-up and monitoring are very important in preventing the malignant transformation of neurofibromatosis. We encountered a case of malignant transformation of plexiform neurofibroma into neurofibrosarcoma (also known as malignant peripheral nerve sheath tumor). She had been presenting with a large mass on her back for a few years, which was also associated with an ulcer. She underwent a wide-excision biopsy of her back, and the histopathology examination (HPE) came back with a malignant peripheral nerve sheath tumor. This case concludes that any patient with a known case of neurofibromatosis should undergo follow-up to detect any malignant transformation of the disease. Early detection of the malignant transformation of neurofibromatosis can help prevent the disease's progression. The main treatment is surgical resection; however, the risk of local recurrence is higher, especially in patients with neurofibromatosis type 1.

Contemporary Approaches to Peripheral Nerve Surgery.

"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.

Le présent manuscrit vise à fournir au lecteur un aperçu général des approches contemporaines de la reconstruction des nerfs périphériques puisque le domaine a beaucoup progressé depuis trois décennies. Les objectifs d'apprentissage s"établissent comme suit : Fournir au lecteur un bref historique de la chirurgie des nerfs périphériques et quelques-unes des avancées historiques qui ont donné lieu aux pratiques de soins actuelles des nerfs périphériques.Décrire les considérations et les possibilités de prise en charge pour les soins des patients ayant une plexopathie brachiale, une lésion médullaire ou une lésion des nerfs périphériques des membres inférieurs.Souligner les techniques chirurgicales contemporaines pour traiter les neurones terminaux et les douleurs des membres fantômes.Examiner les interventions progressives et futures pour les soins des nerfs périphériques, comme l'amplification du transfert du nerf terminal au nerf latéral.Parler des techniques de réadaptation pour les soins des nerfs périphériques.

Upper limb peripheral nerve injuries in patients with ARDS requiring prone positioning: A systematic review with proportion meta-analysis.

OBJECTIVE: To investigate the prevalence of upper limb peripheral nerve injuries (PNI) in adult patients admitted to the intensive care unit (ICU) with acute respiratory distress syndrome (ARDS) undergoing prone positioning. METHODS: This systematic review with meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Four electronic databases including PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, and EMBASE were searched from inception to January 2024. The quality of the included studies was evaluated according to the Joanna Briggs Institute Critical Appraisal Tools. A proportion meta-analysis was conducted to examine the combined prevalence of upper limb PNI among patients requiring prone positioning. RESULTS: A total of 8 studies (511 patients) were pooled in the quantitative analysis. All studies had a low or moderate risk of bias in methodological quality. The overall proportion of patients with upper limb PNI was 13% (95%CI: 5% to 29%), with large between-study heterogeneity (I2 = 84.6%, P<0.001). Both ulnar neuropathy and brachial plexopathy were described in 4 studies. CONCLUSION: During the COVID-19 pandemic, prone positioning has been used extensively. Different approaches among ICU teams and selective reporting by untrained staff may be a factor in interpreting the large variability between studies and the 13% proportion of patients with upper limb PNI found in the present meta-analysis. Therefore, it is paramount to stress the importance of patient assessment both after discharge from the ICU and during subsequent follow-up evaluations. IMPLICATIONS FOR CLINICAL PRACTICE: Specialized training is essential to ensure safe prone positioning, with careful consideration given to arms and head placement to mitigate potential nerve injuries. Therefore, healthcare protocols should incorporate preventive strategies, with patient assessments conducted by expert multidisciplinary teams.

Denosumab combined with chemotherapy followed by anlotinib in the treatment of multiple metastases of malignant peripheral nerve sheath tumor: a case report and literature review.

Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases.

Efficacy and safety of TOMAC for treatment of medication-naïve and medication-refractory restless legs syndrome: A randomized clinical trial and meta-analysis.

OBJECTIVE/BACKGROUND: There is a significant unmet need for safe and effective nonpharmacological therapies for restless legs syndrome (RLS). The objective was to evaluate the efficacy and safety of tonic motor activation (TOMAC) in patients with RLS. PATIENTS/METHODS: A multicenter, randomized, participant-blinded, sham-controlled trial enrolled 45 adults with primary moderate-to-severe RLS who were either medication-naïve (n = 20) or medication-refractory (n = 25). Participants were 1:1 randomized to TOMAC (n = 22) or sham (n = 23) for two weeks and instructed to self-administer 30-min TOMAC sessions when they experienced RLS symptoms. The primary outcome was mean change in International RLS Study Group Rating Scale (IRLS) total score. A subsequent meta-analysis included the present trial and a previous randomized clinical trial that enrolled medication-naïve RLS patients. RESULTS: IRLS reduction was significantly greater for TOMAC than sham (TOMAC -6.59 vs. sham -2.17; mean difference (MD) = -4.42; 95 % confidence interval [CI] -1.57 to -7.26; p = 0.0040). Subgroup analysis showed similar IRLS mean difference for medication-refractory (MD = -4.50; p = 0.02) and medication-naïve (MD = -4.40; p = 0.08) cohorts, which was significantly different from sham only for the medication-refractory cohort. Meta-analysis of combined data from 33 medication-naïve RLS patients showed a significant reduction in mean IRLS score after two weeks for TOMAC compared to sham (MD = -4.30; 95 % CI -1.36 to -7.24; p = 0.004). CONCLUSIONS: The present trial confirmed previous reports documenting efficacy and safety of TOMAC in refractory RLS and indicated similar effect sizes in refractory versus naïve subgroups. The meta-analysis demonstrated that TOMAC significantly improves RLS symptoms in naïve participants.

Core outcomes in nerve surgery: development of a core outcome set for common peroneal (fibular) neuropathy.

OBJECTIVE: Common peroneal (fibular) neuropathy is the most common mononeuropathy of the lower extremity. Despite this, there are surprisingly few studies on the topic, and a knowledge gap remains in the literature. As one attempts to address this knowledge gap, a core outcome set (COS) is needed to guide the planning phases of future studies to allow synthesis and comparability of these studies. The objective of this study was to develop the COS-common peroneal neuropathy (CoPe) using a modified Delphi approach. METHODS: A 5-stage approach was used to develop the COS-CoPe: 1) stage 1, consortium development; 2) stage 2, a literature review to identify potential outcome measures; 3) stage 3, a Delphi survey to develop consensus on outcomes for inclusion; 4) stage 4, a Delphi survey to develop definitions; and 5) stage 5, a consensus meeting to finalize COS and definitions. The study followed the COS-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-CoPe consisted of 31 data points/outcomes covering domains of demographics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 12 months. The consensus optimal time points for assessment were preoperatively and 3, 6, 12, and 24 months postoperatively. CONCLUSIONS: The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-CoPe should serve as a minimum set of data that should be collected in all future neurosurgical studies on common peroneal neuropathy. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.

Dynamic three-dimensional coculture model: The future of tissue engineering applied to the peripheral nervous system.

Traumatic injuries to the peripheral nervous system (PNI) can lead to severe consequences such as paralysis. Unfortunately, current treatments rarely allow for satisfactory functional recovery. The high healthcare costs associated with PNS injuries, worker disability, and low patient satisfaction press for alternative solutions that surpass current standards. For the treatment of injuries with a deficit of less than 30 mm to bridge, the use of synthetic nerve conduits (NGC) is favored. However, to develop such promising therapeutic strategies, in vitro models that more faithfully mimic nerve physiology are needed. The absence of a clinically scaled model with essential elements such as a three-dimension environment and dynamic coculture has hindered progress in this field. The presented research focuses on the development of an in vitro coculture model of the peripheral nervous system (PNS) involving the use of functional biomaterial which microstructure replicates nerve topography. Initially, the behavior of neuron-derived cell lines (N) and Schwann cells (SC) in contact with a short section of biomaterial (5 mm) was studied. Subsequent investigations, using fluorescent markers and survival assays, demonstrated the synergistic effects of coculture. These optimized parameters were then applied to longer biomaterials (30 mm), equivalent to clinically used NGC. The results obtained demonstrated the possibility of maintaining an extended coculture of SC and N over a 7-day period on a clinically scaled biomaterial, observing some functionality. In the long term, the knowledge gained from this work will contribute to a better understanding of the PNS regeneration process and promote the development of future therapeutic approaches while reducing reliance on animal experimentation. This model can be used for drug screening and adapted for personalized medicine trials. Ultimately, this work fills a critical gap in current research, providing a transformative approach to study and advance treatments for PNS injuries.

Enhancing therapeutic potential: Human adipose-derived mesenchymal stem cells modified with recombinant adeno-associated virus expressing VEGF165 gene for peripheral nerve injury.

This study aimed to investigate the therapeutic potential of human adipose-derived mesenchymal stem cells (hADSCs) modified with recombinant adeno-associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate-buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control-hADSCs group), or rAAV VEGF165 vector (VEGF165-hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium-binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165-hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV-VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies.

A tacrolimus-eluting nerve guidance conduit enhances regeneration in a critical-sized peripheral nerve injury rat model.

Critical-sized peripheral nerve injuries pose a significant clinical challenge and lead to functional loss and disability. Current regeneration strategies, including autografts, synthetic nerve conduits, and biologic treatments, encounter challenges such as limited availability, donor site morbidity, suboptimal recovery, potential immune responses, and sustained stability and bioactivity. An obstacle in peripheral nerve regeneration is the immune response that can lead to inflammation and scarring that impede the regenerative process. Addressing both the immunological and regenerative needs is crucial for successful nerve recovery. Here, we introduce a novel biodegradable tacrolimus-eluting nerve guidance conduit engineered from a blend of poly (L-lactide-co-caprolactone) to facilitate peripheral nerve regeneration and report the testing of this conduit in 15-mm critical-sized gaps in the sciatic nerve of rats. The conduit's diffusion holes enable the local release of tacrolimus, a potent immunosuppressant with neuro-regenerative properties, directly into the injury site. A series of in vitro experiments were conducted to assess the ability of the conduit to maintain a controlled tacrolimus release profile that could promote neurite outgrowth. Subsequent in vivo assessments in rat models of sciatic nerve injury revealed significant enhancements in nerve regeneration, as evidenced by improved axonal growth and functional recovery compared to controls using placebo conduits. These findings indicate the synergistic effects of combining a biodegradable conduit with localized, sustained delivery of tacrolimus, suggesting a promising approach for treating peripheral nerve injuries. Further optimization of the design and long-term efficacy studies and clinical trials are needed before the potential for clinical translation in humans can be considered.

Nerve Regeneration Potential of Antioxidant-Modified Black Phosphorus Quantum Dots in Peripheral Nerve Injury.

Peripheral nerve injury is a major societal concern. Black phosphorus (BP) has inherent advantages over cell-based therapies in regenerative medicine. However, controlling spontaneous degradation and size-dependent cytotoxicity remains challenging and poses difficulties for clinical translation. In this study, we constructed zero-dimensional BP quantum dots (QDs) modified with antioxidant ß-carotene and comprehensively investigated them in Schwann cells (SCs) to elucidate their potential for peripheral nerve repair. In vitro experiments demonstrated that BPQD@ß-carotene has an inappreciable toxicity and good biocompatibility, favoring neural regrowth, angiogenesis, and inflammatory regulation of SCs. Furthermore, the PI3K/Akt and Ras/ERK1/2 signaling pathways were activated in SCs at the genetic, protein, and metabolite levels. The BPQD@ß-carotene-embedded GelMA/PEGDA scaffold enhanced functional recovery by promoting axon remyelination and regeneration and facilitating intraneural angiogenesis in peripheral nerve injury models of rats and beagle dogs. These results contribute to advancing knowledge of BP nanomaterials in tissue regeneration and show significant potential for application in translational medicine.