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.

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.

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.

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.

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-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.

Advances in Synthesis and Applications of Self-Healing Hydrogels.

BACKGROUND: Hydrogels, a type of three-dimensional (3-D) crosslinked network of polymers containing a high water concentration, have been receiving increasing attention in recent years. Self-healing hydrogels, which can return to their original structure and function after physical damage, are especially attractive. Some self-healable hydrogels have several kinds of properties such as injectability, adhesiveness, and conductivity, which enable them to be used in the manufacturing of drug/cell delivery vehicles, glues, electronic devices, and so on. MAIN BODY: This review will focus on the synthesis and applications of self-healing hydrogels. Their repair mechanisms and potential applications in pharmaceutical, biomedical, and other areas will be introduced. CONCLUSION: Self-healing hydrogels are used in various fields because of their ability to recover. The prospect of self-healing hydrogels is promising, and they may be further developed for various applications.

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.

(-)-Epigallocatechin gallate-loaded polycaprolactone scaffolds fabricated using a 3D integrated moulding method alleviate immune stress and induce neurogenesis.

OBJECTIVES: In peripheral neuropathy, the underlying mechanisms of nerve and muscle degeneration include chronic inflammation and oxidative stress in fibrotic tissues. (-)-Epigallocatechin gallate (EGCG) is a major, active component in green tea and may scavenge free radical oxygen and attenuate inflammation. Conservative treatments such as steroid injection only deal with early, asymptomatic, peripheral neuropathy. In contrast, neurolysis and nerve conduit implantation work effectively for treating advanced stages. MATERIALS AND METHODS: An EGCG-loaded polycaprolactone (PCL) porous scaffold was fabricated using an integrated moulding method. We evaluated proliferative, oxidative and inflammatory activity of rat Schwann cells (RSCs) and rat skeletal muscle cells (RSMCs) cultured on different scaffolds in vitro. In a rat radiation injury model, we assessed the morphological, electrophysiological and functional performance of regenerated sciatic nerves and gastrocnemius muscles, as well as oxidative stress and inflammation state. RESULTS: RSCs and RSMCs exhibited higher proliferative, anti-oxidant and anti-inflammatory states in an EGCG/PCL scaffold. In vivo studies showed improved nerve and muscle recovery in the EGCG/PCL group, with increased nerve myelination and muscle fibre proliferation and reduced macrophage infiltration, lipid peroxidation, inflammation and oxidative stress indicators. CONCLUSIONS: The EGCG-modified PCL porous nerve scaffold alleviates cellular oxidative stress and repairs peripheral nerve and muscle structure in rats. It attenuates oxidative stress and inflammation in vivo and may provide further insights into peripheral nerve repair in the future.

Advances in electrical and magnetic stimulation on nerve regeneration.

Central and peripheral nerve injuries pose a great threat to people. Complications such as inflammation, muscle atrophy, traumatic neuromas and delayed reinnervation can bring huge challenges to clinical practices and barriers to complete nerve regrowth. Physical interventions such as electrical and magnetic stimulation show satisfactory results with varying parameters for acute and chronic nerve damages. The biological basis of electrical and magnetic stimulation mainly relies on protein synthesis, ion channel regulation and growth factor secretion. This review focuses on the various paradigms used in different models of electrical and magnetic stimulation and their regenerative potentials and underlying mechanisms in nerve injuries. The combination of physical stimulation and conductive biomaterial scaffolds displays an infinite potentiality in translational application in nerve regeneration.

Overexpression of SOX9 alleviates the progression of human osteoarthritis in vitro and in vivo.

PURPOSE: Recent findings have identified that SOX9 served as a key role during the pathogenesis of osteoarthritis (OA). This study aimed to investigate the mechanisms by which SOX9 regulated the formation of OA in vitro and in vivo. MATERIALS AND METHODS: The relative expressions of SOX9 in patients with OA and normal fracture of thighbone were analyzed by real-time-PCR. In vitro, IL-1ß induced inflammatory response in human chondrocytes was used to evaluate the function of SOX9. The recombinant SOX9 lentivirus vector (Lenti-SOX9) was used to upregulate the expression of SOX9 in cells. ELISA was used to measure the concentration of tumor necrosis factor-α (TNF-α). The protein expressions of SOX9, matrix metalloproteinase-13 (MMP13), Collagen II, Aggrecan and Smad3 were analyzed by Western blot. Cell proliferation and cell apoptosis were detected by CCK-8 assay and flow cytometry, respectively. In vivo, the effect of SOX9 on surgically induced OA mice was evaluated. RESULTS: The gene level of SOX9 was remarkably downregulated in patients with OA compared with normal people, while the concentration of TNF-α was upregulated. In addition, IL-1ß reduced the expressions of SOX9, Collagen II and Aggrecan and increased the level of MMP13 in chondrocytes. Moreover, Lenti-SOX9 notably inhibited IL-1ß-induced growth inhibition and apoptosis in chondrocytes via increasing the expression of Smad3. Finally, Lenti-SOX9 markedly alleviated the symptoms of OA mice in vivo. CONCLUSION: Upregulation of SOX9 inhibited IL-1ß-induced inflammatory response via increasing the level Smad3 in human chondrocytes and exhibited therapeutic effect on surgically induced OA mice in vivo. Therefore, SOX9 may serve as a potential target in the treatment of OA in the future.

Effect of gamma irradiation on carbon dot decorated polyethylene-gold@ hydroxyapatite biocomposite on titanium implanted repair for shoulder joint arthroplasty.

High disappointment rate of the ligament to hard tissue mending after the medical procedure has dependably been a testing issue in rotator cuff repair. Considering the elasticity of carbon dot decorated polyethylene (f-CDs-PE) and osteogenic movement of gold substituted hydroxyapatite (Au@HA) bioceramic, f-CDs-PE-Au@HA biocomposite coatings were created by an electrophoretic deposition method (EPD), the in vivo and in vitro bioactivity and cytocompatibility were researched. The physico-chemical properties of f-CDs-PE-Au@HA biocomposite coatings were characterized using fourier transform infra-red (FTIR) and X-Ray diffractometery (XRD). The morphology of the fabricated biocomposites was analyses via scanning electron microscopy (SEM) and transmission electron microscopy (TEM) methods. With a gamma-irradiation of f-CDs-PE-Au@HA biocomposite coating (BC2), the bond and multiplication of cells on biocomposite coating were improved. The specimen with a f-CDs-PE-Au@HA biocomposite (BC2) demonstrated a most noteworthy alkaline phosphatase activity articulation. The animal model consequences additionally show that the f-CDs-PE-Au@HA biocomposite (BC2) had great bioactive and cytocompatibility, which could develop the association of collagen and the arrangement of ligament and hard tissue. Expansion of the gamma-ray irradiation with f-CDs-PE-Au@HA biocomposite coating (BC2) at the tendon- hard tissue crossing point was exhibited to reinforce the mending entheses, increment hard tissue and tendon development and progress collagen association contrasted and control. The above outcomes have recommended that the progressive, implantable and solid stringy platforms built utilizing EPD extraordinary potential for enlargement of rotator cuff tears-recuperating.

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.

3D Fabrication with Integration Molding of a Graphene Oxide/Polycaprolactone Nanoscaffold for Neurite Regeneration and Angiogenesis.

Treating peripheral nerve injury faces major challenges and may benefit from bioactive scaffolds due to the limited autograft resources. Graphene oxide (GO) has emerged as a promising nanomaterial with excellent physical and chemical properties. GO has functional groups that confer biocompatibility that is better than that of graphene. Here, GO/polycaprolactone (PCL) nanoscaffolds are fabricated using an integration molding method. The nanoscaffolds exhibit many merits, including even GO nanoparticle distribution, macroporous structure, and strong mechanical support. Additionally, the process enables excellent quality control. In vitro studies confirm the advantages of the GO/PCL nanoscaffolds in terms of Schwann cell proliferation, viability, and attachment, as well as neural characteristics maintenance. This is the first study to evaluate the in vivo performance of GO-based nanoscaffolds in this context. GO release and PCL biodegradation is analyzed after long-term in vivo study. It is also found that the GO/PCL nerve guidance conduit could successfully repair a 15 mm sciatic nerve defect. The pro-angiogenic characteristic of GO is evaluated in vivo using immunohistochemistry. In addition, the AKT-endothelial nitric oxide synthase (eNOS)-vascular endothelial growth factor (VEGF) signaling pathway might play a major role in the angiogenic process. These findings demonstrate that the GO/PCL nanoscaffold efficiently promotes functional and morphological recovery in peripheral nerve regeneration, indicating its promise for tissue engineering applications.