Chiral MoS2@BC fibrous membranes selectively promote peripheral nerve regeneration.

BACKGROUND: Molybdenum disulfide (MoS2) has excellent physical and chemical properties. Further, chiral MoS2 (CMS) exhibits excellent chiroptical and enantioselective effects, and the enantioselective properties of CMS have been studied for the treatment of neurodegenerative diseases. Intriguingly, left- and right-handed materials have different effects on promoting the differentiation of neural stem cells into neurons. However, the effect of the enantioselectivity of chiral materials on peripheral nerve regeneration remains unclear. METHODS: In this study, CMS@bacterial cellulose (BC) scaffolds were fabricated using a hydrothermal approach. The CMS@BC films synthesized with L-2-amino-3-phenyl-1-propanol was defined as L-CMS. The CMS@BC films synthesized with D-2-amino-3-phenyl-1-propanol was defined as D-CMS. The biocompatibility of CMS@BC scaffolds and their effect on Schwann cells (SCs) were validated by cellular experiments. In addition, these scaffolds were implanted in rat sciatic nerve defect sites for three months. RESULTS: These chiral scaffolds displayed high hydrophilicity, good mechanical properties, and low cytotoxicity. Further, we found that the L-CMS scaffolds were superior to the D-CMS scaffolds in promoting SCs proliferation. After three months, the scaffolds showed good biocompatibility in vivo, and the nerve conducting velocities of the L-CMS and D-CMS scaffolds were 51.2 m/s and 26.8 m/s, respectively. The L-CMS scaffolds showed a better regenerative effect than the D-CMS scaffolds. Similarly, the sciatic nerve function index and effects on the motor and electrophysiological functions were higher for the L-CMS scaffolds than the D-CMS scaffolds. Finally, the axon diameter and myelin sheath thickness of the regenerated nerves were improved in the L-CMS group. CONCLUSION: We found that the CMS@BC can promote peripheral nerve regeneration, and in general, the L-CMS group exhibited superior repair performance. Overall, the findings of this study reveal that CMS@BC can be used as a chiral nanomaterial nerve scaffold for peripheral nerve repair.

Comparison of accuracy for hip-knee-ankle (HKA) angle by X-ray and knee motion analysis system and the relationships between HKA and gait posture.

BACKGROUND: The lower limb mechanical axis was used to assess the severity of knee osteoarthritis (KOA) with varus/valgus deformity and the accuracy of targeted lower limb alignment correction after operation by conventional X-rays. There are lots of parameters to assess the gait in elder patients such as velocity, stride length, step width and swing/stance ratio by knee joint movement analysis system. However, the correlation between the lower limb mechanical axis and gait parameters is not clear. This study is aimed at obtaining the accuracy of the lower limb mechanical axis by the knee joint movement analysis system and the correlation between the lower limb mechanical axis and gait parameters. METHODS: We analysed 3D knee kinematics during ground gait of 99 patients with KOA and 80 patients 6 months after the operations with the vivo infrared navigation 3D portable knee joint movement analysis system (Opti-Knee®, Innomotion Inc, Shanghai, China). The HKA (Hip-Knee-Ankle) value was calculated and compared to X-ray findings. RESULTS: HKA absolute variation after the operation was 0.83 ± 3.76°, which is lower than that before the operation (5.41 ± 6.20°, p = 0.001) and also lower than the entire cohort (3.36 ± 5.72). Throughout the cohort, a significant correlation with low coefficients (r = -0.19, p = 0.01) between HKA value and anterior-posterior displacement was found. In comparing the HKA values measured on the full-length alignment radiographs and 3D knee joint movement analysis system (Opti-Knee), there was a significant correlation with moderate to high coefficients (r = 0.784 to 0.976). The linear correlation analysis showed that there was a significant correlation between the values of HKA measured by X-ray and movement analysis system (R2 = 0.90, p < 0.01). CONCLUSIONS: Data with equivalent results as HKA, the 6DOF of the knee and ground gait data could be provided by infrared navigation based 3D portable knee joint movement analysis system comparing with the conventional X-rays. There is no significant effect of HKA on the kinematics of the partial knee joint.

Enhancement of sciatic nerve regeneration with dual delivery of vascular endothelial growth factor and nerve growth factor genes.

BACKGROUND: Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomically the most challenging to regenerate given its length and large cross-sectional area. For the present, autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. However, this method sacrifices healthy nerves and requires highly intensive surgery, still calling for other advanced alternatives for nerve grafting. RESULTS: In this study, we utilized previously well-established gene delivery system to dually deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), exploring therapeutics for sciatic nerve injury. Low-molecular-weight branched polyethylenimine (bPEI) was constructed as the backbone structure of gene vectors, and it was further crosslinked to synthesize degradable polycations via the conjugation of dialdehydes. Potential synergistic effect between VEGF and NGF proteins were observed on rat sciatic nerve crush injury model in this study. CONCLUSIONS: We concluded that dual delivery of plasmid VEGF and NGF as gene therapy could enhance sciatic nerve regeneration.

3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration.

Peripheral nerve defect is a common and severe kind of injury in traumatic accidents. Melatonin can improve peripheral nerve recovery by inhibiting oxidative stress and inflammation after traumatic insults. In addition, it triggers autophagy pathways to increase regenerated nerve proliferation and to reduce apoptosis. In this study, we fabricated a melatonin-controlled-release scaffold to cure long-range nerve defects for the first time. 3D manufacture of melatonin/polycaprolactone nerve guide conduit increased Schwann cell proliferation and neural expression in vitro and promoted functional, electrophysiological and morphological nerve regeneration in vivo. Melatonin nerve guide conduit ameliorated immune milieu by reducing oxidative stress, inflammation and mitochondrial dysfunction. In addition, it activated autophagy to restore ideal microenvironment, to provide energy for nerves and to reduce nerve cell apoptosis, thus facilitating nerve debris clearance and neural proliferation. This innovative scaffold will have huge significance in the nerve engineering.

The time point in surgical excision of heterotopic ossification of post-traumatic stiff elbow: recommendation for early excision followed by early exercise.

BACKGROUND: Post-traumatic heterotopic ossification (HO) around the elbow may severely impair joint function. Although surgical excision is effective at restoring range of motion (ROM), traditional surgical treatment is postponed for at least 1 year to prevent recurrence, which leads to secondary contracture of the elbow. Because the optimal timing of resection is controversial, our study was performed to compare recurrence and elbow function between early and late excision in our patients to determine whether the delay is necessary. METHODS: We retrospectively reviewed 164 patients during a 4-year period. In the control group (112 patients), HO was excised at an average of 23.0 months after initial injury (range, 9-204 months); in the early excision group (52 patients), resection was performed at an average of 6.1 months (range, 3-8 months). HO recurrence was assessed by the Hastings classification system. Final ROM and Mayo Elbow Performance Scores were also evaluated. RESULTS: Recurrent HO was observed in 30 of 112 patients (26.8%) in the control group and 15 of 52 (28.9%) in early excision group. No significant difference in HO recurrence was found between the 2 groups (P = .942). Moreover, there were no notable differences regarding ROM, Mayo Elbow Performance Scores, and complications postoperatively. CONCLUSIONS: Early excision associated with early exercise is effective for the treatment of HO aiming at a low recurrence rate and satisfactory function. The conventional surgical delay of more than 1 year may be shortened.

Biscarbamate cross-linked low molecular weight Polyethylenimine polycation as an efficient intra-cellular delivery cargo for cancer therapy.

BACKGROUND: A challenge in gene therapy is the efficient delivery of DNA/siRNA to the diseased cells. The physicochemical characteristics of siRNA, such as high molecular weight, negative charges and hydrophilic nature-prevent passive diffusion across the plasma membrane for most cells. A therapeutically feasible carrier for intra-cellular delivery of gene materials should accomplish a series of tasks such as: condensing nucleic acid, protecting nucleic acid from leaking in vivo, facilitating endosome escape and releasing DNA/siRNA to the target site. To meet these requirements, an efficient gene vector based on polycation synthesis for siRNA delivery both in vitro and in vivo was developed. RESULTS: The polymer was synthesized by 1, 4-butanediol bis (chloroformate) and PEI 800 Da to form PEI-Bu which could condense siRNA at the N/P ratio of 38.35 or above. The size of the nanoparticles was 100-300 nm and zeta potential was in the range of 10-30 mV at different N/P ratios. The nanoparticles can achieve the ability of cellular uptake and the silencing efficiency was about 46.63% in SMMC-7721 cell line which was generated to stably express GL3 luciferase gene. The cytotoxicity of the polyplex nanoparticles was almost negligible on SMMC-7721 cells by MTT assay, indicating that the reduced luciferase expression was the effect of RNAi, not the influence of cytotoxicity of polyplexes. The polyplex nanoparticle formulated by PEI-Bu and siRNA at N/P ratio of 115.05 was injected into the SMMC-7721 tumor bearing mice locally and the expression of luciferase can reduce to 63.17% compared with control group. CONCLUSIONS: Results in this study suggested that PEI-Bu polycation might provide a promising solution for siRNA delivery and had the potential in anti-tumor gene therapy.

Uni-directional release of ibuprofen from an asymmetric fibrous membrane enables effective peritendinous anti-adhesion.

Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled in situ loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. In vivo evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.

Endobutton technique for dynamic fixation of traumatic symphysis pubis disruption.

Plate fixation, the conventional treatment for traumatic symphysis pubis disruption, carries the risk of implant failure and demands extensive exposure. The goal of the present study was to evaluate the outcome of dynamic fixation with the Endobutton CL, which has a long successful record in anterior cruciate ligament reconstructions. Twenty-one APC-II injuries were treated from January 2006 to December 2009. The mean duration of follow-up was 23 months (18 to 26). All patients received Endobutton fixation. The incision length was 6.8 +/- 13 cm. The external blood loss was 106 +/- 15 mL. The average surgical time was 63 +/- 12 min. The symphysis distance after reduction was 4.1 +/- 1.2 mm. The symphysis distance at final visit was 4.2 +/- 1.2 mm. Loss of reduction was not significant during bone healing (p = 0.09). The Majeed scoring was excellent in 15 patients, good in 5 patients and fair in 1 patient. One malreduction was seen; there was no implant failure. Our results indicate that Endobutton fixation of the pubic symphysis might be used in the treatment of APC-II injuries.

Non-electric bioelectrical analog strategy by a biophysical-driven nano-micro spatial anisotropic scaffold for regulating stem cell niche and tissue regeneration in a neuronal therapy.

The slow regenerating rate and misdirected axonal growth are primary concerns that disturb the curative outcome of peripheral nerve repair. Biophysical intervention through nerve scaffolds can provide efficient, tunable and sustainable guidance for nerve regrowth. Herein, we fabricate the reduced graphene oxide (rGO)/polycaprolactone (PCL) scaffold characterized with anisotropic microfibers and oriented nanogrooves by electrospinning technique. Adipose-derived stem cells (ADSCs) are seeded on the scaffolds in vitro and the viability, neural differentiation efficiency and neurotrophic potential are investigated. RGO/PCL conduits reprogram the phenotype of seeded cells and efficiently repair 15 mm sciatic nerve defect in rats. In summary, biophysical cues on nerve scaffolds are key determinants to stem cell phenotype, and ADSC-seeded rGO/PCL oriented scaffolds are promising, controllable and sustainable approaches to enable peripheral nerve regeneration.

Graphdiyne-loaded polycaprolactone nanofiber scaffold for peripheral nerve regeneration.

Graphdiyne (GDY) is a kind of nanomaterial from the graphene carbon family with excellent physical and chemical properties. Despite some applications in medical engineering, GDY has not been used as an electroactive scaffold for tissue regeneration because of its unclear in vitro and in vivo biosafety profiles. Here, a conductive GDY nanomaterial-loaded polycaprolactone (PCL) scaffold was prepared by electrospinning technique. For the first time, the biocompatibility of GDY-based scaffold was assessed at the cellular and animal levels in a peripheral nerve injury (PNI) model. The findings indicated that the conductive three-dimensional (3D) GDY/PCL nerve guide conduits (NGCs) could significantly improve the proliferation, adhesion and glial expression of Schwann cells (SCs). The conduits were implanted into a rat 10-mm sciatic nerve defect model for 3 months in vivo. The toxicity of scaffolds to the organs was negligible, while the GDY/PCL NGCs significantly promoted myelination and axonal growth by upregulating the expression levels of SC marker (S100 ß protein), Myelin basic protein (MBP), and axon regeneration marker (ß3-tubulin protein (Tuj1) and neurofilament protein 200 (NF200)). In addition, upregulation of vascular factor expression in GDY/PCL NGC group suggested the potential role in angiogenesis to improve nerve repair by GDY nanomaterials. Our findings provide new perspectives on biocompatibility and effectiveness of GDY nanomaterial scaffold in peripheral nerve regeneration for preclinical application.

An extracellular matrix mimicking alginate hydrogel scaffold manipulates an inflammatory microenvironment and improves peripheral nerve regeneration by controlled melatonin release.

Low efficiency of nerve growth and unstable release of loaded drugs have become a major problem in repairing peripheral nerve injury. Many intervention strategies were focused on simple drug loading, but have still been less effective. The key challenge is to establish a controlled release microenvironment to enable adequate nerve regeneration. In this study, we fabricate a multilayered compound nerve scaffold by electrospinning: with an anti-adhesive outer layer of polycaprolactone and an ECM-like inner layer consisting of a melatonin-loaded alginate hydrogel. We characterized the scaffold, and the loaded melatonin can be found to undergo controlled release. We applied them to a 15 mm rat model of sciatic nerve injury. After 16 weeks, the animals in each group were evaluated and compared for recovery of motor function, electrophysiology, target organ atrophy status, regenerative nerve morphology and relative protein expression levels of neural markers, inflammatory oxidative stress, and angiogenesis. We identify that the scaffold can improve functional ability evidenced by an increased sciatic functional index and nerve electrical conduction level. The antioxidant melatonin loaded in the scaffold reduces inflammation and oxidative stress in the reinnervated nerves, confirmed by increased HO-1 and decreased TNF-α levels in regenerating nerves. The relative expression of fast-type myosin was elevated in the target gastrocnemius muscle. An improvement in angiogenesis facilitates neurite extension and axonal sprouting. This scaffold can effectively restore the ECM-like microenvironment and improve the quality of nerve regeneration by controlled melatonin release, thus enlightening the design criteria on nerve scaffolds for peripheral nerve injury in the future.

Digital pulp reconstruction with free neurovascular toe flaps.

UNLABELLED: Finger pulp defects are commonly encountered in clinical settings and their treatment remains a consistent challenge for plastic and hand surgeons. Reconstruction should restore, as much as possible, the contour of the pulp as well as discriminating sensibility. Following the prime reconstructive principle of replacing "like with like," the free neurovascular toe pulp flap seems to be the optimal choice for digital pulp reconstruction because of the natural similarity of the digital pulp both anatomically and physically. However, after about 30 years of experience with this procedure, it is still controversial because it is technically demanding, involves donor site morbidity, and its reliability is questionable. With other small free flaps available, the application of this flap has been challenged and reconsidered. In this review we specifically focus on the reconstruction of soft tissue defects of digital pulp using the free neurovascular toe flap, aiming to investigate its advantages and drawbacks and obtain a comprehensive understanding of this procedure. The latest reconstruction concerns and technical refinements are also discussed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article.

Using the contralateral reverse less invasive plating system for subtrochanteric femur fractures in elderly patients.

OBJECTIVE: In this retrospective study, we evaluated the efficacy of the reverse less invasive plating system (LISS) in the management of subtrochanteric fractures (STF) in elderly patients that are expected to be difficult to nail. SUBJECTS AND METHODS: Fifty-five patients with STF were treated from April 2005 to December 2007. Of these, 26 (16 females and 10 males, age >65 years, average 79.8 ± 3) had nonpathologic fractures that were internally fixed with a LISS device. The average follow-up period was 24 months (range 15-30). The main outcome measures evaluated were pain, union, varus deformity and implant failure. Radiographic and clinical evidence of functional outcome and complications were also evaluated. RESULTS: Mean perioperative blood loss was 120.5 ± 12 ml (range 65-285), and mean postoperative hospital stay was 7.8 ± 2 days (range 4-14). Using the reverse LISS plates led to complete union of STF in all of the 26 elderly patients without additional procedures. CONCLUSION: Due to advantages like high union rate, early postoperative mobilization and short operation time, the reverse LISS device offers an alternative management of STF in elderly patients unsuitable for nailing procedures.

Graphdiyne-Related Materials in Biomedical Applications and Their Potential in Peripheral Nerve Tissue Engineering.

Graphdiyne (GDY) is a new member of the family of carbon-based nanomaterials with hybridized carbon atoms of sp and sp2, including α, ß, γ, and (6,6,12)-GDY, which differ in their percentage of acetylene bonds. The unique structure of GDY provides many attractive features, such as uniformly distributed pores, highly π-conjugated structure, high thermal stability, low toxicity, biodegradability, large specific surface area, tunable electrical conductivity, and remarkable thermal conductivity. Therefore, GDY is widely used in energy storage, catalysis, and energy fields, in addition to biomedical fields, such as biosensing, cancer therapy, drug delivery, radiation protection, and tissue engineering. In this review, we first discuss the synthesis of GDY with different shapes, including nanotubes, nanowires, nanowalls, and nanosheets. Second, we present the research progress in the biomedical field in recent years, along with the biodegradability and biocompatibility of GDY based on the existing literature. Subsequently, we present recent research results on the use of nanomaterials in peripheral nerve regeneration (PNR). Based on the wide application of nanomaterials in PNR and the remarkable properties of GDY, we predict the prospects and current challenges of GDY-based materials for PNR.

Energy-Supporting Enzyme-Mimic Nanoscaffold Facilitates Tendon Regeneration Based on a Mitochondrial Protection and Microenvironment Remodeling Strategy.

Tendon injury is a tricky and prevalent motor system disease, leading to compromised daily activity and disability. Insufficient regenerative capability and dysregulation of immune microenvironment are the leading causes of functional loss. First, this work identifies persistent oxidative stress and mitochondrial impairment in the regional tendon tissues postinjury. Therefore, a smart scaffold incorporating the enzyme mimicry nanoparticle-ceria nanozyme (CeNPs) into the nanofiber bundle scaffold (NBS@CeO) with porous, anisotropic, and enhanced mechanical properties is designed to innovatively explore a targeted energy-supporting repair strategy by rescuing mitochondrial function and remodeling the microenvironment favoring endogenous regeneration. The integrated CeNPs scavenge excessive reactive oxygen species (ROS), stabilize the mitochondria membrane potential (ΔΨm), and ATP synthesis of tendon-derived stem cells (TDSCs) under oxidative stress. In a rat Achilles tendon defect model, NBS@CeO reduces oxidative damage and accelerates structural regeneration of collagen fibers, manifesting as recovering mechanical properties and motor function. Furthermore, NBS@CeO mediates the rebalance of endogenous regenerative signaling and dysregulated immune microenvironment by alleviating senescence and apoptosis of TDSCs, downregulating the secretion of senescence-associated secretory phenotype (SASP), and inducing macrophage M2 polarization. This innovative strategy highlights the role of NBS@CeO in tendon repair and thus provides a potential therapeutic approach for promoting tendon regeneration.

A multifunctional ATP-generating system by reduced graphene oxide-based scaffold repairs neuronal injury by improving mitochondrial function and restoring bioelectricity conduction.

Peripheral nerve injury usually impairs neurological functions. The excessive oxidative stress and disrupted bioelectrical conduction gives rise to a hostile microenvironment and impedes nerve regeneration. Therefore, it is of urgent need to develop tissue engineering products which help alleviate the oxidative insults and restore bioelectrical signals. Melatonin (MLT) is an important endogenous hormone that diminishes the accumulation of reactive oxygen species. Reduced graphene oxide (RGO) possesses the excellent electrical conductivity and biocompatibility. In this study, a multilayered MLT/RGO/Polycaprolactone (PCL) composite scaffold was fabricated with beaded nanostructures to improve cell attachment and proliferation. It also exhibited stable mechanical properties by high elastic modulus and guaranteed structural integrity for nerve regeneration. The live/dead cell staining and cell counting kit assay were performed to evaluate the toxicity of the scaffold. JC-1 staining was carried out to assess the mitochondrial potential. The composite scaffold provided a biocompatible interface for cell viability and improved ATP production for energy supply. The scaffold improved the sensory and locomotor function recovery by walking track analysis and electrophysiological evaluation, reduced Schwann cell apoptosis and increased its proliferation. It further stimulated myelination and axonal outgrowth by enhancing S100ß, myelin basic protein, ß3-tubulin, and GAP43 levels. The findings demonstrated functional and morphological recovery by this biomimetic scaffold and indicated its potential for translational application.

Compressed Sensing Image Reconstruction of Ultrasound Image for Treatment of Early Traumatic Myositis Ossificans of Elbow Joint by Electroacupuncture.

This article conducts a retrospective analysis of 500 patients with posttraumatic elbow dysfunction admitted to our department from March 2019 to September 2020. The average time from injury to operation is 11 months (2-20 months). We adopt a personalized treatment method to completely remove the hyperplastic adhesion tissue and heterotopic ossification around the joint, remove part of the joint capsule and ligament, and release it to achieve maximum function. After the operation, an external fixator was used to stabilize the loosened elbow joint, and the patient was guided to perform rehabilitation exercises with the aid of a hinged external fixator, and celecoxib was used to prevent heterotopic ossification. Mayo functional scoring system was used to evaluate the curative effect before and after surgery. The rapid realization of ultrasound imaging under the framework of compressed sensing is studied. Under the premise of ensuring the quality of ultrasound imaging reconstruction, the theory of ultrasound imaging is improved, and a plane wave acoustic scattering ultrasound echo model is established. On this basis, the theory of compressed sensing is introduced, the mathematical model of compressed sensing reconstruction is established, and the fast iterative shrinkage thresholding algorithm (FISTA) of compressed sensing reconstruction is improved to reduce the computational complexity and the number of iterations. This article uses FISTA directly to reconstruct medical ultrasound images, and the reconstruction results are not ideal. Therefore, a simulation model of FISTA training and testing was established using the standard image library. By adding different intensities of noise to all images in the image library, the influence of noise intensity on the quality of FISTA reconstructed images is analyzed, and it is found that the FISTA model has requirements for the quality of the images to be reconstructed and the training set images. In this paper, Rob's blind deconvolution restoration algorithm is used to preprocess the original ultrasound image. The clarity of the texture details of the restored ultrasound image is significantly improved, and the image quality is improved, which meets the above requirements. This paper finally formed a reconstruction model suitable for ultrasound images. The reconstruction strategy verified by the ultrasound images provided by the Institute of Ultrasound Imaging of a medical university has achieved a significant improvement in the quality of ultrasound images.

Tacrolimus-Induced Neurotrophic Differentiation of Adipose-Derived Stem Cells as Novel Therapeutic Method for Peripheral Nerve Injury.

Peripheral nerve injuries (PNIs) are frequent traumatic injuries across the globe. Severe PNIs result in irreversible loss of axons and myelin sheaths and disability of motor and sensory function. Schwann cells can secrete neurotrophic factors and myelinate the injured axons to repair PNIs. However, Schwann cells are hard to harvest and expand in vitro, which limit their clinical use. Adipose-derived stem cells (ADSCs) are easily accessible and have the potential to acquire neurotrophic phenotype under the induction of an established protocol. It has been noticed that Tacrolimus/FK506 promotes peripheral nerve regeneration, despite the mechanism of its pro-neurogenic capacity remains undefined. Herein, we investigated the neurotrophic capacity of ADSCs under the stimulation of tacrolimus. ADSCs were cultured in the induction medium for 18 days to differentiate along the glial lineage and were subjected to FK506 stimulation for the last 3 days. We discovered that FK506 greatly enhanced the neurotrophic phenotype of ADSCs which potentiated the nerve regeneration in a crush injury model. This work explored the novel application of FK506 synergized with ADSCs and thus shed promising light on the treatment of severe PNIs.

Preclinical assessment on neuronal regeneration in the injury-related microenvironment of graphene-based scaffolds.

As the application of graphene nanomaterials gets increasingly attractive in the field of tissue engineering and regenerative medicine, the long-term evaluation is necessary and urgent as to their biocompatibility and regenerative capacity in different tissue injuries, such as nerve, bone, and heart. However, it still remains controversial about the potential biological effects of graphene on neuronal activity, especially after severe nerve injuries. In this study, we establish a lengthy peripheral nerve defect rat model and investigate the potential toxicity of layered graphene-loaded polycaprolactone scaffold after implantation during 18 months in vivo. In addition, we further identify possible biologically regenerative effects of this scaffold on myelination, axonal outgrowth, and locomotor function recovery. It is confirmed that graphene-based nanomaterials exert negligible toxicity and repair large nerve defects by dual regulation of Schwann cells and astroglia in the central and peripheral nervous systems. The findings enlighten the future of graphene nanomaterial as a key type of biomaterials for clinical translation in neuronal regeneration.

Polymeric Guide Conduits for Peripheral Nerve Tissue Engineering.

Peripheral nerve injuries (PNIs) are usually caused by trauma, immune diseases, and genetic factors. Peripheral nerve injury (PNI) may lead to limb numbness, muscle atrophy, and loss of neurological function. Although an abundance of theories have been proposed, very few treatments can effectively lead to complete recovery of neurological function. Autologous nerve transplantation is currently the gold standard. Nevertheless, only 50% of all patients were successfully cured using this method. In addition, it causes inevitable damage to the donor site, and available donor sites in humans are very limited. Tissue engineering has become a research hotspot aimed at achieving a better therapeutic effect from peripheral nerve regeneration. Nerve guide conduits (NGCs) show great potential in the treatment of PNI. An increasing number of scaffold materials, including natural and synthetic polymers, have been applied to fabricate NGCs for peripheral nerve regeneration. This review focuses on recent nerve guide conduit (NGC) composite scaffold materials that are applied for nerve tissue engineering. Furthermore, the development tendency of NGCs and future areas of interest are comprehensively discussed.