[Progress on application of hydrogels in the field of peripheral nerve injury repair].

As one of the common traumatic diseases in clinical practice, peripheral nerve injury (PIN) often causes nerve pain, abnormal reflexes, autonomic disorders, and even sensorimotor disorders due to the slow regeneration rate after injury, which seriously affects body function. Even as the gold standard of treatment, autologous nerve transplantation has limitations such as limited donor area and donor injury, which greatly limits its clinical application effect. Therefore, the preparation of artificial nerve grafts suitable for clinical practice has become the future development trend of peripheral nerve injury treatment, and the repair of injury defects and the promotion of nerve regeneration have also become research hotspots in tissue engineering and regenerative medicine. In recent years, extensive research has been carried out on nerve guidance conduits (NGCs) in the field of nerve regeneration and repair, in which scaffold materials and internal fillers have also become the focus of research as the core elements of neural catheters, and a series of achievements have been made in the application of new materials, embedding stem cells/precursor cells, and developing trophic factors and drug-loaded sustained-release systems. Therefore, this paper focuses on the application progress of hydrogel and its related derivative materials in the field of peripheral nerve injury repair, and provides new ideas for promoting the related research of tissue engineering and clinical medicine.

The Immune Regulatory Mechanism of Adrenomedullin on Promoting the Proliferation and Differentiation of Dental Pulp Stem Cells.

OBJECTIVE: This research seeks to analyse the immunomodulatory impacts of adrenomedullin (ADM) on macrophages induced by bacterial lipopolysaccharide and to investigate the influence of macrophage-conditioned media from various stimulating factors on the biological activity of dental pulp stem cells (DPSCs) in vitro. METHODS: The polarisation effect of ADM on macrophages was analysed through cell immunofluorescence staining and flow cytometry. Potential mechanisms were explored through transcriptomics and metabolomics. The impact of different macrophage-conditioned media on the biological activity of DPSCs was evaluated through western blotting, Realtime fluorescence quantitative, alkaline phosphatase activity assay, and eosin red staining. Each experiment was performed with 3 biological and 3 technical duplicate measurements. Statistical analysis was performed with t test and one-way ANOVA, and mathematical significance defined as P < .05. RESULTS: ADM can reverse polarisation of macrophages towards M2 phenotype by Lipopolysaccharide and the conditioned media of ADM-induced M2 polarised macrophages significantly enhances the proliferation and differentiation of DPSCs. The mechanism may involve the metabolic reprogramming of macrophages by ADM, specifically promoting the metabolic shift from glycolysis to mitochondrial oxidative phosphorylation in Lipopolysaccharide-induced macrophages. CONCLUSION: These results indicate that ADM is involved in suppressing inflammation and enhancing the proliferation and differentiation of DPSCs by reprogramming macrophage metabolism.

Operant Conditioning Neuromorphic Circuit With Addictiveness and Time Memory for Automatic Learning.

Most operant conditioning circuits predominantly focus on simple feedback process, few studies consider the intricacies of feedback outcomes and the uncertainty of feedback time. This paper proposes a neuromorphic circuit based on operant conditioning with addictiveness and time memory for automatic learning. The circuit is mainly composed of hunger output module, neuron module, excitement output module, memristor-based decision module, and memory and feedback generation module. In the circuit, the process of output excitement and addiction in stochastic feedback is achieved. The memory of interval between the two rewards is formed. The circuit can adapt to complex scenarios with these functions. In addition, hunger and satiety are introduced to realize the interaction between biological behavior and exploration desire, which enables the circuit to continuously reshape its memories and actions. The process of operant conditioning theory for automatic learning is accomplished. The study of operant conditioning can serve as a reference for more intelligent brain-inspired neural systems.

Honeycomb-inspired ZIF-sealed interface enhances osseointegration via anti-infection and osteoimmunomodulation.

Implant-associated infections (IAIs) pose a significant threat to orthopedic surgeries. Bacteria colonizing the surface of implants disrupt bone formation-related cells and interfere with the osteoimmune system, resulting in an impaired immune microenvironment and osteogenesis disorders. Inspired by nature, a zeolitic imidazolate framework (ZIF)-sealed smart drug delivery system on Ti substrates (ZSTG) was developed for the "natural-artificial dual-enzyme intervention (NADEI)" strategy to address these challenges. The subtle sealing design of ZIF-8 on the TiO2 nanotubes ensured glucose oxidase (GOx) activity and prevented its premature leakage. In the acidic infection microenvironment, the degradation of ZIF-8 triggered the rapid release of GOx, which converted glucose into H2O2 for disinfection. The Zn2+ released from degraded ZIF-8, as a DNase mimic, can hydrolyze extracellular DNA, which further enhances H2O2-induced disinfection and prevents biofilm formation. Importantly, Zn2+-mediated M2 macrophage polarization significantly improved the impaired osteoimmune microenvironment, accelerating bone repair. Transcriptomics revealed that ZSTG effectively suppressed the inflammatory cascade induced by lipopolysaccharide while promoting cell proliferation, homeostasis maintenance, and bone repair. In vitro and in vivo results confirmed the superior anti-infective, osteoimmunomodulatory, and osteointegrative capacities of the ZSTG-mediated NADEI strategy. Overall, this smart bionic platform has significant potential for future clinical applications to treat IAIs.

Dynamic Frame Interpolation in Wavelet Domain.

Video frame interpolation is an important low-level vision task, which can increase frame rate for more fluent visual experience. Existing methods have achieved great success by employing advanced motion models and synthesis networks. However, the spatial redundancy when synthesizing the target frame has not been fully explored, that can result in lots of inefficient computation. On the other hand, the computation compression degree in frame interpolation is highly dependent on both texture distribution and scene motion, which demands to understand the spatial-temporal information of each input frame pair for a better compression degree selection. In this work, we propose a novel two-stage frame interpolation framework termed WaveletVFI to address above problems. It first estimates intermediate optical flow with a lightweight motion perception network, and then a wavelet synthesis network uses flow aligned context features to predict multi-scale wavelet coefficients with sparse convolution for efficient target frame reconstruction, where the sparse valid masks that control computation in each scale are determined by a crucial threshold ratio. Instead of setting a fixed value like previous methods, we find that embedding a classifier in the motion perception network to learn a dynamic threshold for each sample can achieve more computation reduction with almost no loss of accuracy. On the common high resolution and animation frame interpolation benchmarks, proposed WaveletVFI can reduce computation up to 40% while maintaining similar accuracy, making it perform more efficiently against other state-of-the-arts.

Biofilm Microenvironment-Responsive Self-Assembly Nanoreactors for All-Stage Biofilm Associated Infection through Bacterial Cuproptosis-like Death and Macrophage Re-Rousing.

Bacterial biofilm-associated infections (BAIs) are the leading cause of prosthetic implant failure. The dense biofilm structure prevents antibiotic penetration, while the highly acidic and H2 O2 -rich biofilm microenvironment (BME) dampens the immunological response of antimicrobial macrophages. Conventional treatments that fail to consistently suppress escaping planktonic bacteria from biofilm result in refractory recolonization, allowing BAIs to persist. Herein, a BME-responsive copper-doped polyoxometalate clusters (Cu-POM) combination with mild photothermal therapy (PTT) and macrophage immune re-rousing for BAI eradication at all stages is proposed. The self-assembly of Cu-POM in BME converts endogenous H2 O2 to toxic ·OH through chemodynamic therapy (CDT) and generates a mild PTT effect to induce bacterial metabolic exuberance, resulting in loosening the membrane structure of the bacteria, enhancing copper transporter activity and increasing intracellular Cu-POM flux. Metabolomics reveals that intracellular Cu-POM overload restricts the TCA cycle and peroxide accumulation, promoting bacterial cuproptosis-like death. CDT re-rousing macrophages scavenge planktonic bacteria escaping biofilm disintegration through enhanced chemotaxis and phagocytosis. Overall, BME-responsive Cu-POM promotes bacterial cuproptosis-like death via metabolic interference, while also re-rousing macrophage immune response for further planktonic bacteria elimination, resulting in all-stage BAI clearance and providing a new reference for future clinical application.

Influence of ligands within Al-based metal-organic frameworks for selective separation of methane from unconventional natural gas.

Efficient CH4/N2 separation from unconventional natural gas is vital for both energy recycling and climate change control. Figuring out the reason for the disparity between ligands in the framework and CH4 is the crucial problem for developing adsorbents in PSA progress. In this study, a series of eco-friendly Al-based MOFs, including Al-CDC, Al-BDC, CAU-10, and MIL-160, were synthesized to investigate the influence of ligands on CH4 separation through experimental and theoretical analyses. The hydrothermal stability and water affinity of synthetic MOFs were explored through experimental characterization. The active adsorption sites and adsorption mechanisms were investigated via quantum calculation. The results manifested that the interactions between CH4 and MOFs materials were affected by the synergetic effects of pore structure and ligand polarities, and the disparities of ligands within MOFs determined the separation efficiency of CH4. Especially, the CH4 separation performance of Al-CDC with high sorbent selection (68.56), moderate isosteric adsorption heat for CH4 (26.3 kJ/mol), and low water affinity (0.1 g/g at 40% RH) was superior to most porous adsorbents, which was attributed to its nanosheet structure, proper polarity, reduced local steric hindrance, and extra functional groups. The analysis of active adsorption sites indicated that hydrophilic carboxyl groups and hydrophobic aromatic ring were the dominant CH4 adsorption sites for liner ligands and bent ligands, respectively. The methylene groups with saturated C-H bonds enhanced the wdV interaction between ligands and CH4, resulting in the highest binding energy of CH4 for Al-CDC. The results provided valuable guidance for the design and optimization of high-performance adsorbents for CH4 separation from unconventional natural gas.

Enzymatic bionanocatalysts for combating peri-implant biofilm infections by specific heat-amplified chemodynamic therapy and innate immunomodulation.

Bacterial biofilm-associated infection is a life-threatening emergency contributing from drug resistance and immune escape. Herein, a novel non-antibiotic strategy based on the synergy of bionanocatalysts-driven heat-amplified chemodynamic therapy (CDT) and innate immunomodulation is proposed for specific biofilm elimination by the smart design of a biofilm microenvironment (BME)-responsive double-layered metal-organic framework (MOF) bionanocatalysts (MACG) composed of MIL-100 and CuBTC. Once reaching the acidic BME, the acidity-triggered degradation of CuBTC allows the sequential release of glucose oxidase (GOx) and an activable photothermal agent, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). GOx converts glucose into H2O2 and gluconic acid, which can further acidify the BME to accelerate the CuBTC degradation and GOx/ABTS release. The in vitro and in vivo results show that horseradish peroxidase (HRP)-mimicking MIL-100 in the presence of self-supplied H2O2 can catalyze the oxidation of ABTS into oxABTS to yield a photothermal effect that breaks the biofilm structure via eDNA damage. Simultaneously, the Cu ion released from the degraded CuBTC can deplete glutathione and catalyze the splitting of H2O2 into •OH, which can effectively penetrate the heat-induced loose biofilms and kill sessile bacteria (up to 98.64%), such as E. coli and MRSA. Particularly, MACG-stimulated M1-macrophage polarization suppresses the biofilm regeneration by secreting pro-inflammatory cytokines (e.g., IL-6, TNF-α, etc.) and forming a continuous pro-inflammatory microenvironment in peri-implant biofilm infection animals for at least 14 days. Such BME-responsive strategy has the promise to precisely eliminate refractory peri-implant biofilm infections with extremely few adverse effects.

Endowing biodegradable Zinc implants with dual-function of antibacterial ability and osteogenic activity by micro-addition of Mg and Ag (≤ 0.1 wt.%).

Infection remains the devastating complications associated with surgical fixation of bones fractured during trauma. In this study, we report a low-alloyed Zn-Mg-Ag that simultaneously has optimized strength degeneration profiles during degradation, outstanding antibacterial efficacy and osteogenic activity. Our results showed that Zn-0.05Mg-0.1Ag alloy had favorable mechanical properties (UTS: 247.8 ± 1.6 MPa, Elong.: 35 ± 2.2 %) and presented a better hold of mechanical integrity than pure Zn during 28 days corrosion, 2.6 % vs. 18.7 % reduction. After one-year of natural aging, the alloy still preserved an elongation of 24.07 ± 3.84 %. As verified by microbial cultures, Zn-0.05Mg-0.1Ag alloy demonstrated high antibacterial performance against Gram-positive and Gram-negative strains, as well as antibiotic-resistant strains (MRSA) in vitro and in vivo due to the synergistic antibacterial actions of Zn2+ and Ag+. Meanwhile, Zn-Mg-Ag alloy also exhibited enhanced viability, osteogenic differentiation, and gene expressions of osteoblasts in vitro, as well as promoted osteogenic activity than pure Zn in the femoral condyle defect repair model. The co-releasing of Zn, Mg and Ag ions did not induce toxic side effects. Collectively, low alloyed Zn-0.05Mg-0.1Ag indicated long-lasting mechanical integrity during degradation, and presented the ability to synergistically inhibit bacteria and promote osteogenesis, possessing tremendous potential in treating implant-associated infections. STATEMENT OF SIGNIFICANCE: Infection after fracture fixation (IAFF) remains the most common and serious side effects of orthopedic surgery. Additionally, widespread antibiotic use contributes to the development of multi-drug resistant bacteria such as methicillin-resistant staphylococcus aureus (MRSA), which exacerbates IAFF treatment and prevention. IAFF treatment and prevention remain clinically challenging, so implants with dual antibacterial and osteogenic functions are in high demand. The antibacterial efficacy and osteogenic activity of low-alloyed Zn-Mg-Ag (≤0.1 wt.% Mg, Ag) alloys were investigated in vitro and in vivo. The results showed that micro addition of Mg and Ag could significantly improve osseointegration function, mechanical properties, and antibacterial performance. These quantification findings shed new light on the development and understanding of dual functional Zn-based orthopedic implants.

Acidity-Activatable Nanoparticles with Glucose Oxidase-Enhanced Photoacoustic Imaging and Photothermal Effect, and Macrophage-Related Immunomodulation for Synergistic Treatment of Biofilm Infection.

The pH-responsive theragnostics exhibit great potential for precision diagnosis and treatment of diseases. Herein, acidity-activatable nanoparticles of GB@P based on glucose oxidase (GO) and polyaniline are developed for treatment of biofilm infection. Catalyzed by GO, GB@P triggers the conversion of glucose into gluconic acid and hydrogen peroxide (H2 O2 ), enabling an acidic microenvironment-activated simultaneously enhanced photothermal (PT) effect/amplified photoacoustic imaging (PAI). The synergistic effects of the enhanced PT efficacy of GB@P and H2 O2 accelerate biofilm eradication because the penetration of H2 O2 into biofilm improves the bacterial sensitivity to heat, and the enhanced PT effect destroys the expressions of extracellular DNA and genomic DNA, resulting in biofilm destruction and bacterial death. Importantly, GB@P facilitates the polarization of proinflammatory M1 macrophages that initiates macrophage-related immunity, which enhances the phagocytosis of macrophages and secretion of proinflammatory cytokines, leading to a sustained bactericidal effect and biofilm eradication by the innate immunomodulatory effect. Accordingly, the nanoplatform of GB@P exhibits the synergistic effects on the biofilm eradication and bacterial residuals clearance through a combination of the enhanced PT effect with immunomodulation. This study provides a promising nanoplatform with enhanced PT efficacy and amplified PAI for diagnosis and treatment of biofilm infection.

An injectable photo-cross-linking silk hydrogel system augments diabetic wound healing in orthopaedic surgery through spatiotemporal immunomodulation.

BACKGROUND: The complicated hyperglycaemic and chronic inflammation of diabetic wounds in orthopaedic surgery leads to dysregulated immune cell function and potential infection risk. Immune interventions in diabetic wounds face a possible contradiction between simultaneous establishment of the pro-inflammatory microenvironment in response to potential bacterial invasion and the anti-inflammatory microenvironment required for tissue repair. To study this contradiction and accelerate diabetic-wound healing, we developed a photocurable methacryloxylated silk fibroin hydrogel (Sil-MA) system, co-encapsulated with metformin-loaded mesoporous silica microspheres (MET@MSNs) and silver nanoparticles (Ag NPs). RESULTS: The hydrogel system (M@M-Ag-Sil-MA) enhanced diabetic-wound healing via spatiotemporal immunomodulation. Sil-MA imparts a hydrogel system with rapid in situ Ultra-Violet-photocurable capability and allows preliminary controlled release of Ag NPs, which can inhibit bacterial aggregation and create a stable, sterile microenvironment. The results confirmed the involvement of Met in the immunomodulatory effects following spatiotemporal dual-controlled release via the mesoporous silica and Sil-MA. Hysteresis-released from Met shifts the M1 phenotype of macrophages in regions of diabetic trauma to an anti-inflammatory M2 phenotype. Simultaneously, the M@M-Ag-Sil-MA system inhibited the formation of neutrophil extracellular traps (NETs) and decreased the release of neutrophil elastase, myeloperoxidase, and NETs-induced pro-inflammatory factors. As a result of modulating the immune microenvironmental, the M@M-Ag-Sil-MA system promoted fibroblast migration and endothelial cell angiogenesis in vivo, with verification of enhanced diabetic-wound healing accompanied with the spatiotemporal immunoregulation of macrophages and NETs in a diabetic mouse model. CONCLUSIONS: Our findings demonstrated that the M@M-Ag-Sil-MA hydrogel system resolved the immune contradiction in diabetic wounds through spatiotemporal immunomodulation of macrophages and NETs, suggesting its potential as a promising engineered nano-dressing for the treatment of diabetic wounds in orthopaedic surgery.

Bioresponsive nano-antibacterials for H2S-sensitized hyperthermia and immunomodulation against refractory implant-related infections.

There is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial biofilm infections. Here, a novel "gas-sensitized hyperthermia" strategy is proposed for appreciable bacteria killing by the smart design of a metal-organic framework (MOF)-sealed Prussian blue-based nanocarrier (MSDG). Once the biofilm microenvironment (BME) is reached, the acidity-activated MOF degradation allows the release of diallyl trisulfide and subsequent glutathione-responsive generation of hydrogen sulfide (H2S) gas. Upon near-infrared irradiation, H2S-sensitized hyperthermia arising from MSDG can efficiently eliminate biofilms through H2S-induced extracellular DNA damage and heat-induced bacterial death. The generated H2S in the biofilm can stimulate the polarization of macrophages toward M2 phenotype for reshaping immune microenvironment. Subsequently, the secretion of abundant regeneration-related cytokines from M2 macrophages accelerates tissue regeneration by reversing the infection-induced pro-inflammatory environment in an implant-related infection model. Collectively, such BME-responsive nano-antibacterials can achieve biofilm-specific H2S-sensitized thermal eradiation and immunomodulatory tissue remodeling, thus realizing the renaissance of precision treatment of refractory implant-related infections.

Conversion of a Fused or Ankylosed Hip to Total Hip Arthroplasty: Is the Direct Anterior Approach in the Lateral Decubitus Position an Ideal Solution?

BACKGROUND: Total hip arthroplasty (THA) using the direct anterior approach (DAA) is becoming increasingly popular due to its potential benefits over the posterolateral approach (PLA). However, few studies have compared the efficacies of these two surgical approaches in hip fusion treatment. This study compared early clinical direct anterior and posterolateral THA outcomes in hip fusion treatment. METHODS: Here, 127 hips (65 DAA, 62 PLA) were retrospectively evaluated. Early postoperative functional outcomes of DAA and PLA groups were assessed using Harris score and Oxford Hip Score (OHS) and standard anteroposterior hip radiographs. Surgical characteristics, perioperative results, and complications within 6 months postoperatively were recorded. RESULTS: Though baseline values were similar, Harris and OHS scores were better in the DAA group than in the PLA group at 1 and 3 months postoperatively. The average cup anteversion angle was significantly greater in the DAA group than in the PLA group (12.7° vs. 11.1°). More hips undergoing DAA were successfully orientated in both inclination and anteversion angles (46 vs. 32). Early postoperative hip function predictors were preoperative fused hip position, surgical approach, and range of motion. DAA was associated with reduced postoperative blood loss and shorter hospital stays. Furthermore, 14 vs. 8 complications occurred in the DAA vs. PLA group. Lateral femoral cutaneous nerve injuries were observed in eight hips (12.3%) of the DAA group. CONCLUSION: For fused or ankylosed hips, THA using DAA in the lateral decubitus position may result in excellent prosthesis positioning and faster postoperative recovery throughout early follow-up vs. PLA.

Circumferential Decompression Technique of Posterior Endoscopic Cervical Foraminotomy.

OBJECTIVE: Cervical osseous foraminal stenosis (COFS) results from the uncinate process and facet hyperostosis. Currently, the optimal surgical technique for the treatment of COFS remains controversial. MATERIALS AND METHODS: Patients with COFS presenting radiculopathy underwent posterior endoscopic cervical foraminotomy by the circumferential decompression technique. The neck disability index (NDI), the visual analogue scale (VAS), and the modified MacNab criteria were used to evaluate the outcomes. In addition, the range of motion (ROM) and the slippage distance between the operated vertebrae in flexion-extension position were measured to evaluate the stability of the cervical spine. RESULTS: There were 24 consecutive patients in the study. The mean follow-up period was 16.2 months (range: 12-26 months). The NDI and VAS scores for arm/neck pain improved significantly from preoperatively to the last follow-up. The satisfaction rate by modified MacNab criteria was 91.7% on the third postoperative day and 100% on the day of final follow-up. There were no significant differences in intervertebral ROM or slippage distance between the last follow-up and preoperatively (P = 0.968, P = 0.394). Arm pain occurred in one patient, and sustained fingers numbness in two patients, but these symptoms resolved at the last follow-up. CONCLUSIONS: Posterior endoscopic cervical foraminotomy by the circumferential decompression technique is a safe and effective treatment for COFS. Moreover, it preserves the stability and physiological mobility of the cervical spine.

Corrigendum to "Application of 3D Printing-Assisted Articulating Spacer in Two-Stage Revision Surgery for Periprosthetic Infection after Total Knee Arthroplasty: A Retrospective Observational Study".

[This corrects the article DOI: 10.1155/2021/3948638.].

Application of 3D Printing-Assisted Articulating Spacer in Two-Stage Revision Surgery for Periprosthetic Infection after Total Knee Arthroplasty: A Retrospective Observational Study.

BACKGROUND: Bone cement spacers are widely used in two-stage revision surgeries for periprosthetic joint infection (PJI) after total knee arthroplasty. Current spacer design results in insufficient release of drugs; therefore, current spacers have low efficacy. In this study, we explored a set of alternative articular spacer using 3D printing technology. This novel spacer will increase effectiveness of revision surgery for PJI. METHODS: The spacer was designed using CAD software and constructed on site using 3D-printed silicone mold during debridement surgery. We carried out a retrospective study among patients undergoing treatment using traditional static and new articular spacers. Infection control rate, bone loss, difficulty of revision surgery, knee joint range of motion, function evaluation, and subjective satisfaction of the patients in the two groups were compared. RESULTS: Forty-two patients undergoing knee revision surgery between Jan 2014 and Nov 2019 were included in this study. Twenty-two patients were treated with static antibiotic cement spacers, whereas the other twenty patients were with treated with 3D printing-assisted antibiotic loaded articulating spacers. Patients in the articular group showed significantly lower bone loss on the femur site and tibial site compared with patients in the static group. In addition, patients in the articular group showed significantly less operation time, intraoperative blood loss, and improved knee function and patient overall satisfaction compared with patients in the static group. CONCLUSIONS: The 3D printing-assisted articular spacer provides satisfactory range of motion during the interim period, prevents bone loss, facilitates second-stage reimplantation and postoperative rehabilitation, and results in low reinfection and complication rates.