Enhancing fiber-coupling efficiency of beam-to-fiber links in turbulence by spatial non-uniform coherence engineering.

We present a general formula for the fiber-coupling efficiency of various types of non-uniformly correlated beams propagating in a turbulent atmosphere. With it, we calculate the fiber-coupling efficiency of a specific type of non-uniformly correlated beams, Laguerre non-uniformly correlated (LNUC) beams, to investigate how the non-uniform correlation structure plays a role in enhancing the fiber-coupling efficiency. Compared with conventional Gaussian Schell-model beams, the LNUC beams possess better coupling behavior, and the initial coherence length and beam order of such beams can be adjusted to further improve the fiber-coupling efficiency in turbulence. Our results demonstrate how non-uniformly correlated beams can be used for fiber-coupling applications, and demonstrate their intriguing potential for free-space optical communications.

Predicting simultaneously fields of soot temperature and volume fraction in laminar sooting flames from soot radiation measurements - a convolutional neural networks approach.

An original convolutional neural network, i.e. U-net approach, has been designed to retrieve simultaneously local soot temperature and volume fraction fields from line-of-sight measurements of soot radiation fields. A five-stage U-net architecture is established and detailed. Based on a set of N2 diluted ethylene non-premixed flames, the minimum batch size requirement for U-net model training is discussed and the U-net model prediction ability is validated for the first time by fields provided by the modulated absorption emission (MAE) technique documenting the N2 diluted flame. Additionally, the U-net model's flexibility and robustness to noise are also quantitatively studied by introducing 5% & 10% Gaussian random noises into training together with the testing data. Eventually, the U-net predictive results are directly contrasted with those of Bayesian optimized back propagation neural network (BPNN) in terms of testing score, prediction absolute error (AE), soot parameter field smoothness, and time cost.

[Design and Development of Cloud Platform of Emergency COVID-19 Nucleic Acid Detection].

According to the characteristics of short time and large amount of samples for out of hospital emergency nucleic acid detection, this study introduces an out of hospital emergency nucleic acid detection cloud platform system, which realizes the functions of rapid identification of the detected person and one-to-one correspondence with the samples, and real-time upload of the detection results to Zhejiang Government service network for quick viewing and statistics, so as to complete the task of national nucleic acid screening efficiently and accurately that we must provide information support.

High-power vacuum terahertz photomixer and integrated circuits based on microscale phototubes.

Technologies and industrials in long-distance communication, detection, and imaging applications are still in great need of higher-output-power terahertz sources. This paper proposes two kinds of microscale vacuum phototube based high-power terahertz source: vacuum photomixer and terahertz integrated circuit. The principle of photomixer based on photoemission and field-assisted photoemission is demonstrated. Its capability of producing radiation power beyond 1 mW is estimated based on theoretical analysis and experimental evidence. Simulation and theoretical analysis have shown that the fundamental THz photodiode devices can operate with a space-charge limited current density of 4496 A/cm2 at 60 V, and the amplifier circuits are calculated to have a gain performance of around 10 dB. The two photoemission-based roadmaps have the potential to be developed from an emerging and interdisciplinary field to more promising future directions of THz science and technology.

Biomechanical comparison between single-row with triple-loaded suture anchor and suture-bridge double-row rotator cuff repair.

BACKGROUND: Numerous biomechanical and clinical studies comparing different techniques for rotator cuff repair have been reported, yet universal consensus regarding the superior technique has not achieved. A medially-based single-row with triple-loaded suture anchor (also referred to as the Southern California Orthopedic Institute [SCOI] row) and a suture-bridge double-row (SB-DR) with Push-Locks have been shown to result in comparable improvement in treating rotator cuff tear, yet the biomechanical difference is unknown. The purpose of the current study was to determine whether a SCOI row repair had comparable initial biomechanical properties to a SB-DR repair. METHODS: Six matched pairs of fresh-frozen cadaveric shoulders with full-thickness supraspinatus tendon tears we created were included. Two different repairs were performed for each pair (SCOI row and SB-DR methods). Specimens were mounted on a material testing machine to undergo cyclic loading, which was cycled from 10 to 100 N at 1 Hz for 500 cycles. Construct gap formation was recorded at an interval of 50 cycles. Samples were then loaded to failure and modes of failure were recorded. Repeated-measures analysis of variance and pair-t test were used for statistical analyses. RESULTS: The construct gap formation did not differ between SCOI row and SB-DR repairs (P = 0.056). The last gap displacement was 1.93 ± 0.37 mm for SCOI row repair, and 1.49 ± 0.55 mm for SB-DR repair. The tensile load for 5 mm of elongation and ultimate failure were higher for SCOI row repair compared to SB-DR repair (P = 0.011 and 0.028, respectively). The ultimate failure load was 326.34 ± 11.52 N in the SCOI row group, and 299.82 ± 27.27 N in the SB-DR group. Rotator cuff repair with the SCOI row method failed primarily at the suture- tendon interface, whereas pullout of the lateral row anchors was the primary mechanism of failure for repair with the SB-DR method. CONCLUSION: Rotator cuff repair with the SCOI row method has superior biomechanical properties when compared with the SB-DR method. Therefore, SCOI row repair using a medially-based single-row technique with triple-loaded suture anchor is recommended to improve the initial strength in treating full-thickness rotator cuff tears.

[Modeling of Abdominal Wall-Cecum Injury Adhesion and the Anti-adhesion Mechanism of mXG].

OBJECTIVE: To construct the adhesion model of abdominal wall-cecum injury and explore the prevention and treatment effect of modified xyloglucan (mXG) thermosensitive hydrogel on abdominal wall-cecal injury adhesion. METHODS: SD rats were used to construct the abdominal wall-cecal injury adhesion model. Model mice were randomly divided into blank control group (Control), commercial chitosan membrane Control group (Film) and mXG thermosensitive hydrogel group (Hydrogel), each group contained 16 rats.In the Hydrogel group, 1 mL 4% (m/V) mXG solution was smeared on the wound surface of abdominal wall and the cecum, then closed the abdomen after gel was formed (3 min).In the Film group, 2 cm×3 cm chitosan anti-adhesion Film was applied onto the wound surface of the abdominal wall before abdominal closure.In the Control group, 1 mL normal saline was applied onto the wound surface of abdominal wall and the cecum before abdominal closure.On 7 and 14 d after the operation, rats'abdominal cavity was opened by surgery to examine and score the adhesion grade between the abdominal wall and the cecum, with double-blind design.Meanwhile, the adhesion tissue or wound tissue was taken and stained by HE, Masson and Van Gieson to histological evaluate the anti-adhesion effect.The expression of transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) was determined by immunohistochemical staining as well. Another group of 12 SD rat models were subjected to mXG thermosensitive hydrogel intervention.At the 1 and 6 weeks postoperation, rats main organs such as heart, liver, spleen, lung and kidney were taken for histological examination with HE staining for the purpose of evaluation the toxicity of mXG in vivo. RESULTS: Adhesion grade evaluation results showed that Film group rats occurred mild adhesion, Control group rats occurred severe adhesion, while in Hydrogel group hardly rats occured adhesion, and the differences were statistically significant(P < 0.05). Histological results showed that the Hydrogel group rats recovered well at 7 d after surgery.In healing wound tissue, no mutated tissue was observed, but a certain degree of inflammatory cell infiltration was still existed. At 14 d after surgery, the inflammation cells in the wound were significantly reduced, and the healing tissue containing only a small amount of collagen fibers under the neonatal mesothelial layer.But the other two groups showed different degrees of adhesion at the 7 and 14 d post surgery.Immunohistochemical staining showed that the expression of TGF-ß1 and CTGF in the Hydrogel group were both weaker than those in the other groups, and the difference was statistically significant (P < 0.05). In vivo toxicity tests did not show significant changes in the structure of the organs of mXG gel intervention rats at different time points. CONCLUSION: mXG thermosensitive hydrogel plays a good role in physical isolation during the key period of adhesion formation and effectively prevent the occurrence of cecum-abdominal adhesion.

Income related inequality and influencing factors: a study for the incidence of catastrophic health expenditure in rural China.

BACKGROUND: Catastrophic health expenditure (CHE) puts a heavy disease burden on patients' families, aggravating income-related inequality. In an attempt to reduce the financial risks of rural families incurring CHE, China began the New Rural Cooperative Medical System (NCMS) on a trial basis in 2003 and has raised the reimbursement rates continuously since then. Based on statistical data about rural families in sample area of Jiangsu province, this study measures the incidence of CHE, analyzes socioeconomic inequality related to CHE, and explores the influences of the NCMS on the incidence of CHE. METHODS: Statistical data were acquired from two surveys about rural health care, one conducted in 2009 and one conducted in 2010. In 2009, 1424 rural families were analyzed; in 2010, 1796 rural families were analyzed. An index of CHE is created to enable the evaluation of the associated financial risks. The concentration index and concentration curve are used to measure the income-related inequality involved in CHE. Multiple logistic regression is utilized to explore the factors that influence the incidence of CHE. RESULTS: The incidence of CHE decreased from 13.62% in 2009 to 7.74% in 2010. The concentration index of CHE was changed from -0.298 (2009) to -0.323 (2010). Compared with rural families in which all members were covered by the NCMS, rural families in which some members were not covered by the NCMS had a lower incidence of CHE: The odds ratio is 0.65 with a 95% confidence interval of 0.43 to 1.00. For rural families in which all members were covered by the NCMS, the increase in reimbursement rates is correlated to the decline in the incidence of CHE if other influencing factors were controlled: The odds ratio is 0.48 with a 95% confidence interval of 0.36 to 0.64. CONCLUSIONS: Between 2009 and 2010, the incidence rate of CHE in the sampled area decreased sharply, CHE was more concentrated among least wealthy and inequality increased during study period. As of 2010, the poorest rural families still had high risk of experiencing CHE. For rural families in which all members are covered by the NCMS, the rise in reimbursement rates reduces the probability of experiencing CHE.

PCV-VG combined individualized PEEP determination in one-lung ventilated patients with PEEP step change direction: A randomized controlled trial.

INTRODUCTION: The efficacy of pressure-controlled volume-guaranteed ventilation (PCV-VG) combined with a gradient-directional change in positive end-expiratory pressure (PEEP) during one-lung ventilation (OLV) in patients who underwent thoracoscopic surgery was investigated. METHODS: Ninety patients were randomly divided into the PC (PCV-VG + 5 cm H2 O fixed PEEP), PI (PCV-VG + incremental PEEP titration), and PD (PCV-VG + decremental PEEP titration) groups. Hemodynamic (heart rate [HR] and mean arterial pressure [MAP]), respiratory mechanics (Ppeak , Pmean, and Cdyn), and arterial blood gas (pH, PaCO2 , PaO2 , and PaO2 /FiO2 ) indices were evaluated at T1 (10 min of two-lung ventilation [TLV]), T2 (10 min of OLV), and T3 (10 min of recovery, TLV). Enzyme-linked immunosorbent assay was performed to detect neutrophil elastase (NE), clara cell secretory protein (CC16), and interleukin-8 (IL-8) levels at T1 and T3. RESULTS: At T2 and T3 , Ppeak was lower in the PI and PD groups than in the PC group, while Pmean and Cdyn were higher than in the PC group. Ppeak in the PD group was lower than that in the PI group; however, Pmean was higher at T2 and T3 (P < 0.05). At T2 , PaO2 and PaO2 /FiO2 were higher, but PaO2 /FiO2 and VD /VT were lower in the PD and PI groups than in the PC group (P < 0.05). NE, CC16, IL-6, and IL-8 levels were elevated in all three groups at T3 , but the PI and PD groups had lower levels than the PC group (P < 0.05). The incidences of postoperative pulmonary complications (PPCs) and surgical intensive care unit hospitalizations in the PD and PI groups were much lower. CONCLUSION: Gradient-directed altered PEEP titration could improve respiratory mechanics, arterial blood gases, and inflammatory responses and reduce the incidence of PPCs in patients undergoing thoracoscopic surgery.

Protective effects of Pt-N-C single-atom nanozymes against myocardial ischemia-reperfusion injury.

Effective therapeutic strategies for myocardial ischemia/reperfusion (I/R) injury remain elusive. Targeting reactive oxygen species (ROS) provides a practical approach to mitigate myocardial damage following reperfusion. In this study, we synthesize an antioxidant nanozyme, equipped with a single-Platinum (Pt)-atom (PtsaN-C), for protecting against I/R injury. PtsaN-C exhibits multiple enzyme-mimicking activities for ROS scavenging with high efficiency and stability. Mechanistic studies demonstrate that the excellent ROS-elimination performance of the single Pt atom center precedes that of the Pt cluster center, owing to its better synergistic effect and metallic electronic property. Systematic in vitro and in vivo studies confirm that PtsaN-C efficiently counteracts ROS, restores cellular homeostasis and prevents apoptotic progression after I/R injury. PtsaN-C also demonstrates good biocompatibility, making it a promising candidate for clinical applications. Our study expands the scope of single-atom nanozyme in combating ROS-induced damage and offers a promising therapeutic avenue for the treatment of I/R injury.

Insulin-like growth factor binding protein 4 loaded electrospun membrane ameliorating tendon injury by promoting retention of IGF-1.

Tendon injury is one of the most common musculoskeletal disorders that impair joint mobility and lower quality of life. The limited regenerative capacity of tendon remains a clinical challenge. Local delivery of bioactive protein is a viable therapeutic approach for tendon healing. Insulin-like growth factor binding protein 4 (IGFBP-4) is a secreted protein capable of binding and stabilizing insulin-like growth factor 1 (IGF-1). Here, we applied an aqueous-aqueous freezing-induced phase separation technology to obtain the IGFBP4-encapsulated dextran particles. Then, we added the particles into poly (L-lactic acid) (PLLA) solution to fabricate IGFBP4-PLLA electrospun membrane for efficient IGFBP-4 delivery. The scaffold showed excellent cytocompatibility and a sustained release of IGFBP-4 for nearly 30 days. In cellular experiments, IGFBP-4 promoted tendon-related and proliferative markers expression. In a rat Achilles tendon injury model, immunohistochemistry and quantitative real-time polymerase chain reaction confirmed better outcomes by using the IGFBP4-PLLA electrospun membrane at the molecular level. Furthermore, the scaffold effectively promoted tendon healing in functional performance, ultrastructure and biomechanical properties. We found addition of IGFBP-4 promoted IGF-1 retention in tendon postoperatively and then facilitated protein synthesis via IGF-1/AKT signaling pathway. Overall, our IGFBP4-PLLA electrospun membrane provides a promising therapeutic strategy for tendon injury.

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.

Lactoferrin attenuates cardiac fibrosis and cardiac remodeling after myocardial infarction via inhibiting mTORC1/S6K signaling pathway.

Rationale: Myocardial infarction (MI) causes a severe injury response that eventually leads to adverse cardiac remodeling and heart failure. Lactoferrin (Ltf), as a secreted protein, bears multi-pharmacological properties. Present study aims to establish the cardioprotective function and corresponding mechanism of Ltf in MI process. Methods and results: We performed proteomic analysis in Tregs derived from MI heart, and identified Ltf as a remarkably upregulated secreted protein. However, Ltf was decreased in circulation and positively correlated with cardiac function both in mice and patients after MI. Ltf administration remarkably alleviated cardiac fibrosis and remodeling, improved cardiac function, and reduced incidence of heart failure in mice post-MI. In vitro, Ltf suppressed fibroblast to myofibroblast conversion induced by transforming growth factor-ß (TGF-ß). Mechanistically, phosphoproteomic landscape analysis revealed that Ltf repressed the activation of mTORC1/S6K/eIF-4B signaling pathway via interaction with CD74 receptor. Administration of mTORC1/S6K/eIF-4B axis agonist MHY1485 abolished the cardioprotective effects of Ltf. Besides, MHY1485 also markedly reversed the effects of Ltf on suppressing the transformation of fibroblast to myofibroblast mediated by TGF-ß. Conclusion: Our study established the cardiac protective role of Ltf in attenuating cardiac remodeling and improving cardiac function by inhibiting the activation of myofibroblasts through suppressing mTORC1/S6K/eIF-4B signaling pathway post-MI. Treatment with Ltf may serve as a potential novel therapeutic intervention in patients with MI.

Microbiota-derived short-chain fatty acids may participate in post-stroke depression by regulating host's lipid metabolism.

BACKGROUND: Post-stroke depression (PSD) is a common mental disorder of stroke survivors, its pathogenesis remains elusive. Previous studies suggested a role of the microbiota-gut-brain (MGB) axis in stroke and depression. In this study, we characterized microbial composition and function, and gut-brain metabolic signatures, in PSD rats. We aim to explore how disordered gut microbes participate in the pathogenesis of PSD through the MGB axis. MATERIALS AND METHODS: 16S rRNA gene sequence and fecal metabolome analysis were performed to identify the gut microbiome and their functional metabolites in PSD rats. Then, the lipid metabolic signatures in the prefrontal cortex (PFC) of PSD were conducted by liquid chromatography mass spectrometry. Finally, the potential pathway between gut and brain in the onset of PSD were explored. RESULTS: Compared to control and stroke rats, there were 10 genera (most of them belonged to phylum Firmicutes) significantly changed and 3 short chain fatty acids (SCFAs: butyric acid, acetic acid and pentanoic acid) significantly decreased in PSD rats. Meanwhile, altered gut microbial in PSD rats was significantly associated with these SCFAs. Compared with control and stroke rats, 57 lipid metabolites in the PFC of PSD rats were significantly changed. In addition, the altered SCFAs in PSD rats were also significantly correlated with most of disordered lipid metabolites in PFC. CONCLUSIONS: Our findings suggest that the SCFAs may be a bridge of gut-brain communication. The Firmicutes-SCFAs-lipid metabolism might be a potential pathway to further investigate the MGB axis and pathogenesis of PSD.

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.

Hippocampal Galectin-3 knockdown alleviates lipopolysaccharide-induced neurotoxicity and cognitive deficits by inhibiting TLR4/NF-кB signaling in aged mice.

Neuroinflammation is thought to contribute to the onset and progression of Alzheimer's disease (AD). Galectin-3 (Gal-3), the only member of the galectin chimeric subfamily, is a key regulator of neuroinflammation and microglial activation. However, the effects of Gal-3 inhibition in AD-related neuroinflammation are unclear. Here, we investigated whether hippocampal Gal-3 knockdown alleviated lipopolysaccharide (LPS)-induced neurotoxicity and cognitive deficits, as well as the underlying mechanisms. First, we bilaterally injected aged mice (23 months old) with anti-Gal-3 short hairpin RNA into the hippocampus dentate gyrus, followed by systemic LPS administration. To determine the effects of hippocampal Gal-3 knockdown on neuroinflammatory response and neuronal apoptosis, we assessed the effects of Gal-3 silencing on the levels of pro-inflammatory cytokines, microglial activation, and apoptosis in the hippocampus of LPS-exposed aged mice. Behavioral tests were used to access the cognitive function of the mice. To explore the potential signaling, protein extracts from the brains of mice were subjected to analyze the expression levels of key molecules (including Toll-like receptor 4 (TLR4), myeloid differentiation factor 88, and nuclear transcription factor-κB (NF-κB) p65) of the TLR4/NF-кB pathway, and BV2 cells were pretreated with TLR4 inhibitor or NF-κB inhibitor before Gal-3 stimulation. These analyses showed that hippocampal Gal-3 knockdown attenuated neuroinflammation and neuronal apoptosis in the hippocampus of LPS-challenged aged mice, and this was associated with improved cognitive function. Hippocampal Gal-3 knockdown may protect against LPS-induced neurotoxicity by inhibiting the TLR4/NF-кB pathway. Our findings highlight Gal-3 as a potential therapeutic target against AD-associated neuroinflammation.

Graphene Family Nanomaterials for Stem Cell Neurogenic Differentiation and Peripheral Nerve Regeneration.

Stem cells play a critical role in peripheral nerve regeneration. Nerve scaffolds fabricated by specific materials can help induce the neurogenic differentiation of stem cells. Therefore, it is a potential strategy to enhance therapeutic efficiency. Graphene family nanomaterials are widely applied in repairing peripheral nerves. However, the mechanism underlying the pro-regeneration effects remains elusive. In this review, we first discuss the properties of graphene family nanomaterials, including monolayer and multilayer graphene, few-layer graphene, graphene oxide, reduced graphene oxide, and graphene quantum dots. We also introduce their applications in regulating stem cell differentiation. Then, we review the potential mechanisms of the neurogenic differentiation of stem cells facilitated by the materials. Finally, we discuss the existing challenges in this field to advance the development of nerve biomaterials.

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.

Biomechanically-Adapted Immunohydrogels Reconstructing Myelin Sheath for Peripheral Nerve Regeneration.

Myelin sheath reconstruction plays an important role in peripheral nerve regeneration. But the hindered reconstruction of myelin sheath, due to the inadequate repair phenotypes of macrophages and Schwann cells after peripheral nerve injury, often causes poor functional nerve recovery. Here, biomechanically-adapted immunohydrogels are prepared as the FK506-loaded platforms and nerve tissue engineering scaffolds to reconstruct myelin sheath for peripheral nerve regeneration. By immunofluorescent staining, an increase in the proportion of F4/80+ markers reveals that the biomechanically-adapted scaffolds facilitate recruitment of macrophages. Furthermore, the high Interleukin 10 (IL-10) mRNA expression level suggests the anti-inflammation learning effects of FK506 in vitro, which is further confirmed by a high CD206/TNF-α ratio in the FK506 Gel group in vivo. The immune learning effects are positively related to the increase in compactness and thickness of myelin sheath, indicating the synergy of structural reconstruction of myelin sheath and M2 phenotype polarization of macrophages. All these data indicate that the biomechanically-adapted immunohydrogels enhance recruitment of macrophages, educate M2 polarization of macrophages and promote a neuroprotective environment, which in consequence reconstructs myelin sheath for peripheral nerve regeneration.

Biomimicry in 3D printing design: implications for peripheral nerve regeneration.

Nerve guide conduits (NGCs) connect dissected nerve stumps and effectively repair short-range peripheral nerve defects. However, for long-range defects, autografts show better therapeutic effects, despite intrinsic limitations. Recent evidence shows that biomimetic design is essential for high-performance NGCs, and 3D printing is a promising fabricating technique. The current work includes a brief review of the challenges for peripheral nerve regeneration. The authors propose a potential solution using biomimetic 3D-printed NGCs as alternative therapies. The assessment of biomimetic designs includes microarchitecture, mechanical property, electrical conductivity and biologics inclusion. The applications of 3D printing in preparing NGCs and present strategies to improve therapeutic effects are also discussed.

Two-Dimensional Nanomaterials for Peripheral Nerve Engineering: Recent Advances and Potential Mechanisms.

Peripheral nerve tissues possess the ability to regenerate within artificial nerve scaffolds, however, despite the advance of biomaterials that support nerve regeneration, the functional nerve recovery remains unsatisfactory. Importantly, the incorporation of two-dimensional nanomaterials has shown to significantly improve the therapeutic effect of conventional nerve scaffolds. In this review, we examine whether two-dimensional nanomaterials facilitate angiogenesis and thereby promote peripheral nerve regeneration. First, we summarize the major events occurring after peripheral nerve injury. Second, we discuss that the application of two-dimensional nanomaterials for peripheral nerve regeneration strategies by facilitating the formation of new vessels. Then, we analyze the mechanism that the newly-formed capillaries directionally and metabolically support neuronal regeneration. Finally, we prospect that the two-dimensional nanomaterials should be a potential solution to long range peripheral nerve defect. To further enhance the therapeutic effects of two-dimensional nanomaterial, strategies which help remedy the energy deficiency after peripheral nerve injury could be a viable solution.