Topographic Cues Guiding Cell Polarization via Distinct Cellular Mechanosensing Pathways.

Cell polarization exists in a variety of tissues to regulate cell behaviors and functions. Space constraint (spatially limiting cell extension) and adhesion induction (guiding adhesome growth) are two main ways to induce cell polarization according to the microenvironment topographies. However, the mechanism of cell polarization induced by these two ways and the downstream effects on cell functions are yet to be understood. Here, space constraint and adhesion induction guiding cell polarization are achieved by substrate groove arrays in micro and nano size, respectively. Although the morphology of polarized cells is similar on both structures, the signaling pathways to induce the cell polarization and the downstream functions are distinctly different. The adhesion induction (nano-groove) leads to the formation of focal adhesions and activates the RhoA/ROCK pathway to enhance the myosin-based intracellular force, while the space constraint (micro-groove) only activates the formation of pseudopodia. The enhanced intracellular force caused by adhesion induction inhibits the chromatin condensation, which promotes the osteogenic differentiation of stem cells. This study presents an overview of cell polarization and mechanosensing at biointerface to aid in the design of novel biomaterials.

Transcutaneous electrical acupoint stimulation for post-traumatic stress disorder: Assessor-blinded, randomized controlled study.

AIM: Transcutaneous electrical acupoint stimulation (TEAS) has the potential to alleviate post-traumatic stress disorder (PTSD). The purpose of this study was to determine whether adding TEAS to sertraline or cognitive behavioral therapy (CBT) could improve the anti-PTSD efficacy. METHODS: In this randomized controlled trial, 240 PTSD patients (60 in each group) were assigned to receive simulated TEAS combined with sertraline (group A) or with CBT (group B), active TEAS combined with CBT (group C), or active TEAS combined with CBT plus sertraline (group D) for 12 weeks. The outcomes were measured using the Clinician-Administered PTSD Scale, PTSD Check List-Civilian Version, and 17-item Hamilton Rating Scale for Depression. RESULTS: While PTSD symptoms reduced over time in all patients, groups C and D had markedly greater improvement in both PTSD and depressive measures than groups A and B in all post-baseline measurement points, with moderate to very large effect sizes of 0.484-2.244. Groups C and D also had a significantly higher rate than groups A and B on clinical response (85.0% and 95.0% vs 63.3% and 60.0%, P < 0.001) and on remission (15.0% and 25.0% vs 3.3% and 1.7%, P < 0.001). The incidence of adverse events was similar between groups A and D and between groups B and C. CONCLUSIONS: Additional TEAS augments the anti-PTSD and antidepressant efficacy of antidepressants or CBT, without increasing the incidence of adverse effects. TEAS could serve as an effective intervention for PTSD and comorbid depression. This trial was registered with www.chictr.org (no.: ChiCTR1800017255).

Periodic Lamellae-Based Nanofibers for Precise Immunomodulation to Treat Inflammatory Bone Loss in Periodontitis.

Periodontitis is a common oral disease accompanied by inflammatory bone loss. The pathological characteristics of periodontitis usually accompany an imbalance in the periodontal immune microenvironment, leading to difficulty in bone regeneration. Therefore, effective treatment strategies are needed to modulate the immune environment in order to treat periodontitis. Here, highly-oriented periodic lamellae poly(ε-caprolactone) electrospun nanofibers (PLN) are developed by surface-directed epitaxial crystallization. The in vitro result shows that the PLN can precisely modulate macrophage polarization toward the M2 phenotype. Macrophages polarized by PLN significantly enhance the migration and osteogenic differentiation of Bone marrow stromal cells. Notably, results suggest that the topographical cues presented by PLN can modulate macrophage polarization by activating YAP, which reciprocally inhibits the NF-κB signaling pathway. The in vivo results indicate that PLN can inhibit inflammatory bone loss and facilitate bone regeneration in periodontitis. The authors' findings suggest that topographical nanofibers with periodic lamellae is a promising strategy for modulating immune environment to treat inflammatory bone loss in periodontitis.

Association of M-Type Phospholipase A2 Receptor Deposition in Kidney Tissue with Treatment Outcomes in Patients with Idiopathic Membranous Nephropathy.

Objective: The purpose of this study was to investigate the correlation between the deposition of M-type phospholipase A2 receptor (PLA2R) in the kidney tissues of patients with idiopathic membranous nephropathy (IMN). Method: We enrolled a total of 61 patients diagnosed with IMN in the past 8 years who were admitted at the Jinjiang Municipal Hospital and the 2nd Affiliated Hospital of Fujian Medical University. PLA2R immunofluorescence was used to stain kidney tissues, and all patients were treated with steroid combined with immunosuppressive agents or conservative regimens. The duration of follow-up was more than 48 weeks. Based on the deposition of PLA2R in kidney tissues, we divided the patients into the PLA2R Positive group and the PLA2R Negative group. Further, patients with PLA2R-positive kidney tissues were divided into "1+", "2+", and "3+" groups based on the extent of their PLA2R deposition, and we compared the therapeutic outcomes of the various groups. Results: At week 12 of follow-up, the partial remission rate of kidney tissues in the PLA2R Negative group was significantly higher than that in the Positive group (P = 0.004). Among the various deposition groups with PLA2R-positive kidney tissues, the complete remission rate of the "2+" group was higher than that of the "3+" group at weeks 24, 36, and 48 of follow-up (P < 0.05). In IMN patients treated with a combination regimen of steroid and tacrolimus, the complete remission rate in kidney tissues of the PLA2R Negative group was higher than that of the Positive group at weeks 24 and 48 of follow-up (P < 0.05). Conclusion: The overall effective rate of treatment in kidney tissues of PLA2R-negative patients was higher than that in the kidney tissues of PLA2R-positive patients. The varied levels of PLA2R deposition in kidney tissues were related to the treatment outcomes of IMN, and those with lower PLA2R deposition levels had better outcomes.

Polycaprolactone Electrospun Nanofiber Membrane with Sustained Chlorohexidine Release Capability against Oral Pathogens.

Multiple-pathogen periodontal disease necessitates a local release and concentration of antibacterial medication to control inflammation in a particular location of the mouth cavity. Therefore, it is necessary to effectively load and deliver medicine/antibiotics to treat numerous complex bacterial infections. This study developed chlorhexidine (CHX)/polycaprolactone (PCL) nanofiber membranes with controlled release properties as periodontal dressings to prevent or treat oral disorders. Electrostatic spinning was adopted to endow the nanofiber membranes with a high porosity, hydrophilicity, and CHX loading capability. The release of CHX occurred in a concentration-dependent manner. The CHX/PCL nanofiber membranes exhibited good biocompatibility with human periodontal ligament stem cells, with cell viability over 85% in each group via CCK-8 assay and LIVE/DEAD staining; moreover, the good attachment of the membrane was illustrated by scanning electron microscopy imaging. Through the agar diffusion assay, the nanofiber membranes with only 0.075 wt% CHX exhibited high antibacterial activity against three typical oral infection-causing bacteria: Porphyromonas gingivalis, Enterococcus faecalis, and Prevotella intermedia. The results indicated that the CHX/PCL nanofiber holds great potential as a periodontal dressing for the prevention and treatment periodontal disorders associated with bacteria.

Mucosa-Like Conformal Hydrogel Coating for Aqueous Lubrication.

Mucosa is a protective and lubricating barrier in biological tissue, which has a great clinical inspiration because of its slippery, soft, and hydrophilic surface. However, mimicking mucosal traits on complex surface remains an enormous challenge. Herein, a novel approach to create mucosa-like conformal hydrogel coating is developed. A thin conformal hydrogel layer mimicking the epithelial layer is obtained by first absorbing micelles, followed by forming covalent interlinks with the polymer substrate via interface-initiated hydrogel polymerization. The resulting coating exhibits uniform thickness (≈15 µm), mucosa-matched compliance (Young's modulus = 1.1 ± 0.1 kPa) and lubrication (coefficients of friction = 0.018 ± 0.003), robust interfacial bonding against peeling (peeling strength = 1218.0 ± 187.9 J m-2 ), as well as high water absorption capacity. It effectively resists adhesion of proteins and bacteria without compromising biocompatibility. As demonstrated by an in vivo cynomolgus monkey model and clinical trial, applications of the mucosa-like conformal hydrogel coating on the endotracheal tube significantly reduce intubation-related complications, such as invasive stimuli, mucosal lesions, laryngeal edema, inflammation, and postoperative pain. This work offers a promising prototype for surface decoration of biomedical devices and holds great prospects for clinical translation to enable interventional operations with minimally invasive impacts.

Surface Epitaxial Nano-Topography Facilitates Biomineralization to Promote Osteogenic Differentiation and Osteogenesis.

Biomimetic modification of hydroxyapatite on a polymer surface is a potent strategy for activating biological functions in bone tissue engineering applications. However, the polymer surface is bioinert, and it is difficult to introduce a uniform calcium phosphate (CaP) layer. To overcome this limitation, we constructed a specific nano-topographical structure onto a poly(ε-caprolactone) substrate via surface-directed epitaxial crystallization. Formation of the CaP layer on the nano-topological surface was enhanced by 2.34-fold compared to that on a smooth surface. This effect was attributed to the abundant crystallization sites for CaP deposition because of the increased surface area and roughness. Bone marrow mesenchymal stromal cells (BMSCs) were used to examine the biological effect of biomineralized surfaces. We clearly demonstrated that BMSCs responded to surface biomineralization. Osteogenic differentiation and proliferation of BMSCs were significantly promoted on the biomineralized nano-topological surface. The expression of alkaline phosphatase and osteogenic-related genes as well as extracellular matrix mineralization was significantly enhanced. The proposed strategy shows potential for designing bone repair scaffolds.

Highly Thermally Conductive Graphene-Based Thermal Interface Materials with a Bilayer Structure for Central Processing Unit Cooling.

Innovations of transistors toward miniaturization and integration aggravate heat accumulation of central processing units (CPUs). Thermal interface materials (TIMs) are critical to remove the generated heat and to guarantee the device reliability. Herein, maltose-assisted mechanochemical exfoliation was proposed to prepare maltose-g-graphene as a structural motif of TIMs. Then, maltose-g-graphene/gelatin composite films with a bilayer structure were prepared by two-step vacuum filtration to construct effective thermally conductive pathways consisting of the directionally arranged and tightly packed maltose-g-graphene. The bilayer composite film exhibited a remarkable in-plane thermal conductivity (30.8 W m-1 K-1) and strong anisotropic ratio (∼8325%) at 40 wt % maltose-g-graphene addition. More intriguingly, the cooling effect on CPUs was significantly better for the bilayer composite films than commercial thermal pads as TIMs. The outstanding thermally conductive stability in resistance to instantaneous and prolonged thermal shocks as well as fatigue stability was gathered. Our work offers a valuable reference to design and fabricate high-performance TIMs for CPU cooling to surmount harsh application scenarios.

Promoted Bone Regeneration by 3D-Printed Porous Scaffolds with the Synergy of a Nanotopological Morphology and Amino Modification.

Three-dimensional (3D)-printed scaffolds have great advantages for bone repair, and the combination of physical and chemical modifications of the surface can improve deficient biological properties to promote bone regeneration. In this study, a nanotopological morphology and an amino group were introduced into scaffold surfaces in sequence by alkaline solution and amination, respectively. The surface properties and the ability for osteogenic induction were investigated. The nanotopological morphology of the surface slightly enhanced the hydrophilic property of the material, while amination obviously increased the hydrophilicity of the surface. The aminated surface improved cell adhesion and proliferation, while the nanotopological morphology was able to facilitate the spread of stem cells, pseudopod extension, and osteogenic differentiation by changing the cell skeleton. The study confirmed that a nanotopological morphology and an amino group can play synergistic roles in improving the osteogenic efficiency and hydrophilicity, which was also confirmed in vivo by showing that effective surface modification of polylactic acid scaffolds enhanced high-quality bone formation, thus demonstrating great potential for clinical applications. The results indicate that scaffolds with the synergy of a nanotopological morphology and amino modification improve the osteogenic induction ability of scaffolds.