Advances in preparation and application of antibacterial hydrogels.

Bacterial infections, especially those caused by drug-resistant bacteria, have seriously threatened human life and health. There is urgent to develop new antibacterial agents to reduce the problem of antibiotics. Biomedical materials with good antimicrobial properties have been widely used in antibacterial applications. Among them, hydrogels have become the focus of research in the field of biomedical materials due to their unique three-dimensional network structure, high hydrophilicity, and good biocompatibility. In this review, the latest research progresses about hydrogels in recent years were summarized, mainly including the preparation methods of hydrogels and their antibacterial applications. According to their different antibacterial mechanisms, several representative antibacterial hydrogels were introduced, such as antibiotics loaded hydrogels, antibiotic-free hydrogels including metal-based hydrogels, antibacterial peptide and antibacterial polymers, stimuli-responsive smart hydrogels, and light-mediated hydrogels. In addition, we also discussed the applications and challenges of antibacterial hydrogels in biomedicine, which are expected to provide new directions and ideas for the application of hydrogels in clinical antibacterial therapy.

A hSCARB2-transgenic mouse model for Coxsackievirus A16 pathogenesis.

BACKGROUND: Coxsackievirus A16 (CA16) is one of the neurotropic pathogen that has been associated with severe neurological forms of hand, foot, and mouth disease (HFMD), but its pathogenesis is not yet clear. The limited host range of CA16 make the establishment of a suitable animal model that can recapitulate the neurological pathology observed in human HFMD more difficult. Because the human scavenger receptor class B, member 2 (hSCARB2) is a cellular receptor for CA16, we used transgenic mice bearing human SCARB2 and nasally infected them with CA16 to study the pathogenicity of the virus. METHODS: Coxsackievirus A16 was administered by intranasal instillation to groups of hSCARB2 transgenic mice and clinical signs were observed. Sampled at different time-points to document and characterize the mode of viral dissemination, pathological change and immune response of CA16 infection. RESULTS: Weight loss and virus replication in lung and brain were observed in hSCARB2 mice infected with CA16, indicating that these animals could model the neural infection process. Viral antigens were observed in the alveolar epithelia and brainstem cells. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes into the alveolar interstitial in lung and diffuse punctate hemorrhages in the capillaries of the brainstem. In addition, we detected the expression levels of inflammatory cytokines and detected high levels of interleukin IL-1ß, IL-6, IL-18, and IFN-γ in nasal mucosa, lungs and brain tissues. CONCLUSIONS: The hSCARB2-transgenic mice can be productively infected with CA16 via respiratory route and exhibited a clear tropism to lung and brain tissues, which can serve as a model to investigate the pathogenesis of CA16 associated respiratory and neurological disease.

Freely Moldable Modified Starch as a Sustainable and Recyclable Plastic.

Efficiently preparing a starch-based plastic with moisture insensitivity and toughness is a challenge to improve the high-value utilization of polysaccharide resources. Herein, a sustainable, recyclable starch-based plastic was prepared in a facile and eco-friendly way. First, starch acetoacetate (SAA) with different degrees of substitution (DSs) was synthesized by transesterification. Then, the SAA film was obtained through a solvent-free hot-pressing method. Notably, SAA with different DSs exhibited various glass transition temperatures (109-140 °C), and SAA with high DS (>0.84) was insoluble even after boiling in water for 1 h. Also, the maximum fracture strength of SAA film up to 15.5 MPa and a maximum elongation at break up to 30% were reached . In addition, the starch-based plastic film retained the original mechanical properties after three cycles of hot processing. In consideration of the facile preparation process, this protocol provided a new avenue for developing sustainable and recyclable starch-based plastics.

Transcatheter Arterial Sclerosing Embolization for the Treatment of Giant Propranolol-Resistant Infantile Hemangiomas in the Parotid Region.

PURPOSE: To report the effectiveness and safety of transcatheter arterial sclerosing embolization (TASE) for the treatment of parotid infantile hemangiomas that did not respond appreciably to propranolol. MATERIALS AND METHODS: A total of 21 infants (12 male and 9 female) with large propranolol-resistant infantile hemangiomas in the parotid region were enrolled in this study. During TASE, the feeding arteries of the lesions were embolized using pingyangmycin-lipiodol emulsion and polyvinyl alcohol particles (300-500 µm) to reduce the blood flow rate. All children were followed up as outpatients at 2 weeks and monthly thereafter. The curative effect was evaluated at the 1- and 3-month follow-up visits. RESULTS: Nine lesions were located on the right side of the parotid gland, whereas 12 were located on the left side. The feeding arteries in all patients originated from branches of the external carotid artery. TASE was technically successful in all patients. The mean (± SD) maximal diameter of the hemangiomas significantly decreased from 6.50 cm ± 2.28 before treatment to 3.56 cm ± 1.84 at 1 month after TASE (P <. 05). Three months after TASE, the mean maximal diameter further significantly decreased to 1.94 cm ± 1.58 (P <. 05). During the follow-up period, 16 cases were rated as excellent and 5 as good; no recurrence or serious complications were noted. Minor side effects, such as slight pain, mild fever, and tissue swelling, were observed. CONCLUSIONS: TASE significantly decreased the size of the parotid hemangiomas with minor side effects during a short follow-up period.

Polidocanol Sclerotherapy for the Treatment of Pyogenic Granuloma in Children.

BACKGROUND: Pyogenic granuloma (PG) is a benign vascular lesion that is commonly observed in the skin and mucosa. Sclerotherapy is the first-line conservative treatment option for PG. OBJECTIVE: This retrospective study aimed to evaluate the efficacy of sclerotherapy with 1.0% polidocanol for the treatment of PG. MATERIALS AND METHODS: All patients who were clinically diagnosed with PG consecutively at the Pediatric Outpatient Service of Qilu Children's Hospital of Shandong University from March 2018 to October 2019 received sclerotherapy with 1.0% polidocanol. RESULT: The procedure resulted in the complete excision of PG, with inconspicuous scars. The procedure was well-tolerated, and recurrence was not observed. Allergic reactions, cutaneous necrosis, and pigmentary changes were not observed. CONCLUSION: Sclerotherapy with 1.0% polidocanol is considered an effective treatment for PGs in children. Early treatment was associated with a more favorable outcome.

Suppression of the toll-like receptor 7-dependent type I interferon production pathway by autophagy resulting from enterovirus 71 and coxsackievirus A16 infections facilitates their replication.

Toll-like receptors (TLRs) act as molecular sentinels, detecting invading viral pathogens and triggering host innate immune responses, including autophagy. However, many viruses have evolved a series of strategies to manipulate autophagy for their own benefit. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16), as the primary agents causing hand, foot and mouth disease (HFMD), can induce autophagy leading to their replication. Therefore, the objective of this study was to investigate whether enhanced viral replication caused by autophagy in EV71 and CA16 infections was associated with a TLR-related signaling pathway. Our results demonstrate that complete autophagy and incomplete autophagy were observed in human bronchial epithelial (16HBE) cells infected with EV71 and CA16. Moreover, suppression of autophagy by the pharmacological modulator 3-MA significantly and clearly decreased the survival rates and viral replication of EV71 and CA16 in 16HBE cells. Inhibition of autophagy also enhanced the expression of molecules related to the TLR7-dependent type I interferon (IFN-I) production pathway, such as TLR7, MyD88, IRF7 and IFN-α/ß. Finally, immunofluorescence staining demonstrated that TLR7 endosome marker M6PR levels were clearly reduced in EV71- and CA16-infected cells, while they were markedly elevated in infected cells treated with 3-MA. These findings suggest that increased EV71 and CA16 replication meditated by autophagy in 16HBE cells might promote degradation of the endosome, leading to suppression of the TLR7-mediated IFN-I signaling pathway.

An inactivated enterovirus 71 vaccine in healthy children.

BACKGROUND: Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71. RESULTS: A total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the intention-to-treat analysis and 97.3% (95% CI, 92.6 to 99.0) according to the per-protocol analysis. Adverse events, such as fever (which occurred in 41.6% of the participants who received vaccine vs. 35.2% of those who received placebo), were significantly more common in the week after vaccination among children who received the vaccine than among those who received placebo. CONCLUSIONS: The inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease. (Funded by the National Basic Research Program and others; ClinicalTrials.gov number, NCT01569581.).

Peptide-Coated Semiconductor Polymer Dots for Stem Cells Labeling and Tracking.

Stem cell therapy is rapidly moving toward translation to clinical application. To elucidate the therapeutic effect, a robust method that allows tracking of the stem cells over an extended period of time is required. Herein, semiconducting polymer dots (Pdots) are demonstrated for their use in bright labeling and tracking of human mesenchymal stem cells (MSCs) in vitro and in vivo. The Pdots coated with a cell-penetrating peptide (R8) showed remarkable endocytic uptake efficiency that was 15 times higher than that of carboxyl Pdots and more than 200 times than that of bare Pdots. The Pdot-labeled MSCs can be traced for 15 generations in vitro and tracked over 2 weeks in vivo after subcutaneous transplantation. The labeled MSCs administered through the tail vein were preferentially accumulated in the lung; this was distinctive from the distribution of free Pdots, which were primarily distributed in the liver. Based on the properties of bright labeling, excellent tracking capability, and great biocompatibility, the Pdots will be valuable in the applications of stem cell biology and regenerative medicine.

Poor performance of Enduron polyethylene liner in total hip arthroplasty: a minimum ten-year follow up and ultra-morphological analysis of wear particles.

PURPOSE: The aim of the present study was to investigate the long-term outcome and the wear characteristics of two distinct types of ultra-high molecular weight polyethylene (UHMWPE) liners in total hip arthroplasty (THA). METHODS: We conducted a retrospective clinical study on patients which were treated with total hip arthroplasty using either Enduron polyethylene (Enduron PE) or Trilogy polyethylene (Trilogy PE) liners based on a minimum of ten year follow up data. Morphological analyses of wear particles from tissue samples, which were harvested during revision surgeries, were also performed. RESULTS: A total of 79 THAs in the Enduron group and 55 THAs in the Trilogy group were available for analysis. Kaplan-Meier survival with revision for wear-related complications as the endpoint of the Enduron PE liners was lower than that of Trilogy PE liners at ten years (93.5 % and 100 %, P = 0.03). The Enduron group had higher mean linear wear rate than that of the Trilogy group (0.20 ± 0.09 and 0.09 ± 0.03 mm/year, P < 0.01). The incidence of osteolysis for the Enduron group was higher than that of the Trilogy group (33.3 % and 12 %, P = 0.04). Under transmission electron microscopy, the Enduron group had more than 82 % of the particles less than 1.0 µm in size and more than 57 % of the particles less than 0.5 µm. CONCLUSION: The long-term performance of Enduron liners was worse than that of Trilogy liners. Further clinical follow-up may be necessary in patients with Enduron PE liners in order to avoid catastrophic complications.

Thermoresponsive AuNPs Stabilized by Pillararene-Containing Polymers.

Pillararene-containing thermoresponsive polymers are synthesized via reversible addition-fragmentation chain transfer polymerization using pillararene derivatives as the effective chain transfer agents for the first time. These polymers can self-assemble into micelles and form vesicles after guest molecules are added. Furthermore, such functional polymers can be further applied to prepare hybrid gold nanoparticles, which integrate the thermoresponsivity of polymers and molecular recognition of pillararenes.

Reconstruction of Block Copolymer Micelles to Long-Range Ordered Dense Nanopatterns Via Light-Tunable Hydrogen-Bonding Association.

Controlling the orientation and long-range order of nanostructures is a key issue in the self-assembly of block copolymer micelles. Herein, a versatile strategy is presented to transform one-component oxime-based block copolymer micelles into long-range ordered dense nanopatterns. Photoisomerization provides a straightforward and versatile approach to convert the hydrogen-bonding association from inward dimerization (E-type oxime motifs, slightly desolvated in ethyl acetate) into outward interchain association (Z-type ones, highly desolvated in ethyl acetate). This increases the glass transition temperature in bulk and converts swollen micelles into compact spherical micelles in solution. The reconstruction of these micelles on various substrates demonstrates that the phase transformation enables reconstruction of spherical micelles into mesoscopic sheets, nanorods, nanoworms, nanowires, networks, and eventually into long-range ordered and densely packed textile-like and lamellar nanopatterns on a macroscopic scale by adjusting E/Z-oxime ratio and solvent-evaporation rate.

Construction and Self-Assembly of Single-Chain Polymer Nanoparticles via Coordination Association and Electrostatic Repulsion in Water.

Simultaneous coordination-association and electrostatic-repulsion interactions play critical roles in the construction and stabilization of enzymatic function metal centers in water media. These interactions are promising for construction and self-assembly of artificial aqueous polymer single-chain nanoparticles (SCNPs). Herein, the construction and self-assembly of dative-bonded aqueous SCNPs are reported via simultaneous coordination-association and electrostatic-repulsion interactions within single chains of histamine-based hydrophilic block copolymer. The electrostatic-repulsion interactions are tunable through adjusting the imidazolium/imidazole ratio in response to pH, and in situ Cu(II)-coordination leads to the intramolecular association and single-chain collapse in acidic water. SCNPs are stabilized by the electrostatic repulsion of dative-bonded block and steric shielding of nonionic water-soluble block, and have a huge specific surface area of function metal centers accessible to substrates in acidic water. Moreover, SCNPs can assemble into micelles, networks, and large particles programmably in response to the solution pH. These unique media-sensitive phase-transformation behaviors provide a general, facile, and versatile platform for the fabrication of enzyme-inspired smart aqueous catalysts.

Upregulation of cell proliferation via Shc and ERK1/2 MAPK signaling in SaOS-2 osteoblasts grown on magnesium alloy surface coating with tricalcium phosphate.

Magnesium (Mg) alloys have been demonstrated to be viable orthopedic implants because of mechanical and biocompatible properties similar to natural bone. In order to improve its osteogenic properties, a porous ß-tricalcium phosphate (ß-TCP) was coated on the Mg-3AI-1Zn alloy by alkali-heat treatment technique. The human bone-derived cells (SaOS-2) were cultured on (ß-TCP)-Mg-3AI-1Zn in vitro, and the osteoblast response, the morphology and the elements on this alloy surface were investigated. Also, the regulation of key intracellular signalling proteins was investigated in the SaOS-2 cells cultured on alloy surface. The results from scanning electron microscope and immunofluorescence staining demonstrated that (ß-TCP)-Mg-3AI-1Zn induced significant osteogenesis. SaOS-2 cell proliferation was improved by ß-TCP coating. Moreover, the (ß-TCP)-Mg-3AI-1Zn surface induced activation of key intracellular signalling proteins in SaOS-2 cells. We observed an enhanced activation of Src homology and collagen (Shc), a common point of integration between bone morphogenetic protein 2, and the Ras/mitogen-activated protein kinase (MAPK) pathway. ERK1/2 MAP kinase activation was also upregulated, suggesting a role in mediating osteoblastic cell interactions with biomaterials. The signalling pathway involving c-fos (member of the activated protein-1) was also shown to be upregulated in osteoblasts cultured on the (ß-TCP)-Mg-3AI-1Zn. These results suggest that ß-TCP coating may contribute to successful osteoblast function on Mg alloy surface. (ß-TCP)-Mg-3AI-1Zn may upregulate cell proliferation via Shc and ERK1/2 MAPK signaling in SaOS-2 osteoblasts grown on Mg alloy surface.

Enhancing gene transfection of poly(ß-amino ester)s through modulation of amphiphilicity and chain sequence.

Poly(ß-amino ester)s (PAEs) have emerged as a type of highly safe and efficient non-viral DNA delivery vectors. However, the influence of amphiphilicity and chain sequence on DNA transfection efficiency and safety profile remain largely unexplored. In this study, four PAEs with distinct amphiphilicity and chain sequences were synthesized. Results show that both amphiphilicity and chain sequence significantly affect the DNA binding and condensation ability of PAEs, as well as size, zeta potential and cellular uptake of PAE/DNA polyplexes. PAEs with different amphiphilicity and chain sequence exhibit cell type-dependent transfection capabilities: in human bladder transitional cell carcinoma (UM-UC-3), hydrophilic PAE (P-Philic) and amphiphilic PAE random copolymer (R-Amphilic) exhibit relatively higher gene transfection efficiency, while in human bladder epithelial immortalized cells (SV-HUC-1), hydrophobic PAE (P-Phobic), R-Amphilic, and amphiphilic PAE block copolymer (B-Amphilic) demonstrate higher transfection capability. Regardless of cell types, amphiphilic PAE block copolymer (B-Amphilic) always exhibits much lower gene transfection efficiency. In addition, in human colon cancer cells (HCT-116), P-Philic and R-Amphilic achieved superior gene transfection efficiency at high and low polymer/DNA weight ratios, respectively. Importantly, R-Amphilic can effectively deliver the gene encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to human chondrosarcoma cells SW1353 to induce their apoptosis, highlighting its potential application in cancer gene therapy. This study not only establishes a new paradigm for enhancing the gene transfection efficiency of PAEs by modulating their amphiphilicity and chain sequence but also identifies R-Amphilic as a potential candidate for the effective delivery of TRAIL gene in cancer gene therapy.

[In vitro evaluation of antibacterial activity and cytocompatibility of antibacterial stainless steel containing copper].

To study the in vitro antibacterial activity and biocompatibility of 317L stainless steel containing 4.5% copper alloy (317L-Cu), we produced 317L-Cu stainless steel with epsilon-Cu phase. The cell proliferation of osteoblasts on material surface was detected in vitro. Escherichia coli was cultured with 317L-Cu for evaluating the antibacterial activity. We found that the 317L-Cu could effectively kill the Escherichia coli on material surface. The cell proliferation of osteoblasts on material surface was not different significantly, compared with titanium material. Our study clearly demonstrated that the 317L-Cu alloys had a significant antimicrobial activity and was biocompatible in vitro, so it would be suitable to be used as a new medical material with antibacterial activity.

Evaluation of Biodegradable Alloy Fe30Mn0.6N in Rabbit Femur and Cartilage through Detecting Osteogenesis and Autophagy.

Biodegradable iron alloy implants have become one of the most ideal possible candidates because of their biocompatibility and comprehensive mechanical properties. Iron alloy's impact on chondrocytes is still unknown, though. This investigation looked at the biocompatibility and degradation of the Fe30Mn0.6N alloy as well as how it affected bone formation and chondrocyte autophagy. In vivo implantation of Fe30Mn0.6N and Ti6Al4V rods into rabbit femoral cartilage and femoral shaft was carried out to evaluate the degradation of the alloy and the cartilage and bone response at different intervals. After 8 weeks of implantation, the cross-sectional area of the Fe30Mn0.6N alloys lowered by 50.79 ± 9.59%. More Ca and P element deposition was found on the surface Fe30Mn0.6N rods by using energy dispersive spectroscopy (EDS) and scanning electron microscopy (P < 0.05). After 2, 4, and 8 weeks of implantation, no evident inflammatory infiltration was seen in peri-implant cartilage and bone tissue of Fe30Mn0.6N and Ti6Al4V alloys. Also, implantation of Fe30Mn0.6N alloy promoted autophagy in cartilage by detecting expression of LC3-II compared with Ti6Al4V after implantation (P < 0.05). Fe30Mn0.6N alloy also stimulated early osteogenesis at the peri-implant interface compared with Ti6Al4V after implantation (P < 0.05). In the in vitro test, we found that low concentrations of Fe30Mn0.6N extracts had no influence on cell viability. 15% and 30% extracts of Fe30Mn0.6N could upregulate autophagy compared to the control group by detecting beclin-1, LC3, Atg3, and P62 on the basis of WB and IHC (P < 0.05). Also, the PI3K-AKT-mTOR signaling pathway mediated in the upregulation of autophagy of chondrocytes resulting in exposure to extract of Fe30Mn0.6N alloy. It is concluded that Fe30Mn0.6N showed degradability and biocompatibility in vivo and upregulated autophagy activity in chondrocytes.

Recent advance in biomass membranes: Fabrication, functional regulation, and antimicrobial applications.

Both inorganic and polymeric membranes have been widely applied for antimicrobial applications. However, these membranes exhibit low biocompatibility, weak biodegradability, and potential toxicity to human being and environment. Biomass materials serve as excellent candidates for fabricating functional membranes to address these problems due to their unique physical, chemical, and biological properties. Here we present recent progress in the fabrication, functional regulation, and antimicrobial applications of various biomass-based membranes. We first introduce the types of biomass membranes and their fabrication methods, including the phase inversion, vacuum filtration, electrospinning, layer-by-layer self-assembly, and coating. Then, the strategies on functional regulation of biomass membranes by adding 0D, 1D, and 2D nanomaterials are presented and analyzed. In addition, antibacterial, antifungal, and antiviral applications of biomass-based functional membranes are summarized. Finally, potential development aspects of biomass membranes are discussed and prospected. This comprehensive review is valuable for guiding the design, synthesis, structural/functional tailoring, and sustainable utilization of biomass membranes.

Development of a novel patient-reported outcome measure for orthognathic surgery.

OBJECTIVES: This study aimed to develop a new patient-reported outcome measure (PROM) to systematically and scientifically evaluate patients' subjective feelings after orthognathic surgery. METHODS: A literature review and semi-structured interviews were conducted to construct a conceptual framework and an item pool, followed by expert and patient surveys for measure construction. We conducted a clinical investigation to test the feasibility, reliability, and content validity of this measure. RESULTS: The conceptual framework included four domains: psychological health, physiological health, social function, and satisfaction, and 33 items were included in the survey. Following the expert analysis, 31 items remained in the draft. The clinical investigation showed a 100% recovery and completion rate and good reliability, with Cronman-Brown formula coefficients of 0.893 and 0.944, respectively. CONCLUSIONS: A new outcome measure to evaluate patients' subjective feelings after orthognathic surgery was successfully developed, and the clinical investigation demonstrated that the PROM had satisfactory feasibility, reliability, and validity. Further studies are possible based on our PROM, and data on a larger scale may reveal more information on patients' subjective feelings about orthognathic surgery. CLINICAL SIGNIFICANCE: The novel PROM provides a systematic and scientific way to evaluate the patient's subjective feelings to help surgeons obtain complete patient-reported information after orthognathic surgery. Additionally, standardised multicentre research on patients' subjective feelings using our PROM is possible and could improve the effectiveness of the evaluation and help maintain treatment quality.