Profiling patient-reported symptom recovery from oesophagectomy for patients with oesophageal squamous cell carcinoma: a real-world longitudinal study.

PURPOSE: Oesophageal squamous cell carcinoma (ESCC) patients have severe symptom burden after oesophagectomy; however, longitudinal studies of symptom recovery after surgery are scarce. This study used longitudinal patient-reported outcome (PRO)-based symptoms to identify severe symptoms and profile symptom recovery from surgery in patients undergoing oesophagectomy. METHODS: Oesophageal cancer patients (N = 327) underwent oesophagectomy were consecutively included between April 2019 and March 2020. Data were extracted from the Sichuan Cancer Hospital's Esophageal Cancer Case Management Registration Database. Symptom assessment time points were pre-surgery and 1, 3, 5, 7, 14, 21, 30, and 90 days post-surgery using the Chinese version of the MD Anderson Symptom Inventory. And each symptom was rated on an 11-point scale, with 0 being 'not present' and 10 being 'as bad as you can imagine'. The symptom recovery trajectories were profiled using mixed effect models and Kaplan-Meier analysis. RESULTS: The most-severe symptoms on day 1 after oesophagectomy were pain, fatigue, dry mouth, disturbed sleep, and distress. The severity of symptoms peaked on day 1 after surgery. The top two symptoms were fatigue (mean: 5.44 [SD 1.88]) and pain (mean: 5.23 [SD 1.29]). Fatigue was more severe 90 days after surgery than at baseline (mean: 1.77 [SD 1.47] vs 0.65 [SD 1.05]; P < .0001). Disturbed sleep and distress persisted from pre-surgery to 90 days post-surgery; average sleep recovery time was up to 20 days, and 50.58% of patients had sleep disturbances 90 days post-surgery. CONCLUSIONS: Early post-operative pain management after oesophagectomy should be considered. Characteristics and intervention strategies of post-operative fatigue, distress, and disturbed sleep in oesophageal cancer patients warrant further studies.

Non-thermal plasma reduces periodontitis-induced alveolar bone loss in rats.

Periodontitis, a chronic infectious disease induced by microbial biofilm, is one of the most common diseases worldwide. Scaling and root planning (SRP) has always been recognized as the typical treatment. However, the therapeutic efficiency is often limited due to the intraoperative bleeding and the limitations of instruments. Non-thermal atmospheric plasma (NTP) appears to be a potential tool for periodontitis due to its promising biofilm degradation and decontamination effects. In this study, we investigated the role of NTP, as an adjuvant approach for the treatment of ligature-induced periodontitis in rats. Herein we showed that SRP or SRP-NTP application attenuated the periodontitis-induced alveolar bone loss, reflected by the increased BV/TV value and the decreased CEJ-AB distance, which might be related to the lower detection rate of periodontal pathogen in SRP and SRP-NTP groups. Besides, SRP-NTP rats showed less bone loss and lower CEJ-AB distance than that of SRP group at 30d post treatment, indicating a more comprehensive and long-lasting effect of SRP-NTP. A remarkable decrease of osteoclast number and lower expression of RANKL was also detected in SRP-NTP rats. In addition, expression of inflammatory-related cytokines such as TNF-α and IL-1ß decreased significantly in SRP-NTP group, while IL-10 level increased substantially. These results together illustrated that a combination of SRP and NTP treatment was an effective way to prevent periodontitis progress, which reduced alveolar bone loss and promoted periodontium restoration in ligature-induced periodontitis rats. In conclusion, non-thermal plasma treatment may be considered as a feasible and effective supplementary approach to control periodontitis.

Tumor Specific and Renal Excretable Star-like Triblock Polymer-Doxorubicin Conjugates for Safe and Efficient Anticancer Therapy.

Efficient tumor accumulation and body clearance are two paralleled requirements for ideal nanomedicines. However, it is hard for both to be met simultaneously. The inefficient clearance often restrains the application of drug delivery systems (DDSs), especially for high-dosage administration. In this study, the star-like and block structures are combined to enhance the tumor specific targeting of the parent structures and obtain additional renal excretion property. The influences of polymer architectures and chemical compositions on the physicochemical and biological properties, particularly the simultaneous achievement of tumor accumulation and renal clearance, have been investigated. Among the tested conjugates, an eight-arm triblock star polymer based on poly(ethylene glycol) (PEG) and poly( N-(2-hydroxyl) methacrylamide) (PHPMA) is found to simultaneously fulfill the requirements of superior tumor accumulation and efficient renal clearance due to the appropriate micelle size and reversible aggregation process. On the basis of this conjugate, 60 mg/kg of Dox equivalent (much higher than the maximum tolerated dose (MTD) of Dox) can be administered to efficiently suppress tumor growth without causing any obvious toxicity. This work provides a new approach to design polymer-drug conjugates for tumor specific application, which can simultaneously address the efficacy and safety concerns.

Shell-Sheddable Poly(N-2-hydroxypropyl methacrylamide) Polymeric Micelles for Dual-Sensitive Release of Doxorubicin.

Poly(ethylene glycol) (PEG) shell-sheddable micelles are proved to be effective tools for rapid intracellular drug delivery. However, some adverse factors, such as the potential immunogenicity and the accelerated blood clearance, might be accompanied with the traditional PEG sheddable micelles. Here, a poly(N-2-hydroxypropyl methacrylamide) (PHPMA) sheddable block copolymer containing disulfide bonds on the main chain is prepared to form pH- and reduction-dual-responsive micelles. The most optimal synthetic route of the block copolymer is selected from three potential pathways. Doxorubicin is loaded via an acid-labile hydrazone bond to achieve high drug loading content and to prevent premature drug release. As expected, as-prepared shell-sheddable micelles exhibit faster intracellular drug release and more satisfactory in vitro anticancer efficacy than the nonsheddable counterpart did. This design provides a feasible guideline for the efficient synthesis of similar shell-sheddable micelles consisting of PHPMA coatings.

Efficient Tumor Accumulation, Penetration and Tumor Growth Inhibition Achieved by Polymer Therapeutics: The Effect of Polymer Architectures.

To obtain high tumor-specific accumulation, strong tumor penetration and low off-target uptake, we developed a series of polymer therapeutics with different architectures, including random, block, and brush-like structure, based on the classic N-(2-hydroxypropyl) methacrylamide polymers. The influence of polymer architecture on biological properties such as cellular uptake, blood clearance, and biodistribution have been investigated. Besides small micelles whose sizes were determined by polymer architectures, large aggregates formed by micelle aggregation could also be observed. Although they had different architectures, the drug release rate, endocytic pathways and cellular uptake level of various conjugates have been proved to be identical. The polymer architecture of various conjugates lay great impact on the blood clearance, biodistribution and tumor growth inhibition. We assumed that the differences in in vivo biological properties were coordinately caused by the different size of the small aggregates and the formation and stability of large aggregates for different conjugates. Even though the reason was still unclear, the results inspired us that only by diblock conjugates with improved cellular uptake can we realize tumor specific accumulation, deep penetration, and efficient tumor inhibition.

Effect of hydrophobic surface treated fumed silica fillers on a one-bottle etch and rinse model dental adhesive.

The objective of this study was to investigate the effect of hydrophobic surface treatment to fumed silica fillers on the bonding performance of a one-bottle etch and rinse model dental adhesive. In this study, 0.5-5 wt.% of Filler 1 and Filler 2 were loaded into BisGMA/HEMA model dental adhesive. Filler 1 was not treated, while Filler 2 was surface treated with a dimethyl silicone fluid making the silica extremely hydrophobic. The prepared adhesives were characterized through measurements of viscosity, degree of conversion, and water contact angle. SEM was utilized to observe the microstructures at the bonding interface. Micro-tensile bond strength (µTBS) test coupled with fracture surface analysis was carried out to study the mechanical properties. From the experiment, the loadings of Filler 2 is favorable to the improvement of µTBS. The µTBS of experimental adhesive with 1 wt.% Filler 2 increased 42% compared to the model adhesive without filler, and 24% compared to the experimental adhesive with 1 wt.% Filler 1. The effectively penetration of the hydrophobic compositions of the adhesive is considered as the main reason that leads to the increased bond strength, which was proved by the contact angle measurement and SEM observations.

Effects of trimethylsilane plasma coating on the hydrophobicity of denture base resin and adhesion of Candida albicans on resin surfaces.

STATEMENT OF PROBLEM: Candida-associated denture stomatitis is the most common oral mucosal lesion among denture wearers. Trimethylsilane (TMS) plasma coating may inhibit the growth of Candida albicans on denture surfaces. PURPOSE: The purpose of this in vitro study was to investigate whether TMS plasma coatings can effectively reduce C albicans adhesion on denture base acrylic resin surfaces. MATERIAL AND METHODS: Sixty denture base acrylic resin disks with smooth and rough surfaces were prepared and were either left untreated (control group) or coated with TMS monomer (experimental group) by using plasma. Contact angles were measured immediately after TMS plasma coating. The morphology of C albicans adhesion was observed with scanning electron microscopy (SEM). Energy-dispersive spectroscopy (EDS) was used to characterize the elemental composition of the specimen surface. An adhesion test was performed by incubating the resin disk specimens in C albicans suspensions (1×107 cells/mL) at 37°C for 24 hours and further measuring the optical density of the C albicans by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay test. One-way ANOVA and 2-way ANOVA were followed by a post hoc test analysis (α=.05). RESULTS: The group with TMS coating exhibited a more hydrophobic surface than the control group. EDS analysis revealed successful TMS plasma coating. The difference in the mean contact angles between the uncoated group and the TMS-coated group was statistically significant (P<.05), 79.0 ±2.9 degrees versus 105.7 ±1.5 degrees for the smooth surface and 90.2 ±7.6 degrees versus 131.5 ±2.1 degrees for the rough surface. In SEM analysis, the C albicans biofilm was found to grow more on the surface of the denture base resin without the TMS coating than on the surfaces of the experimental group. In the adhesion test, the amount of C albicans adhering to the surface of denture base resin with the TMS coating was significantly less than that on the surfaces without TMS coating (P<.05). CONCLUSIONS: TMS coating significantly reduced the adhesion of C albicans to the denture base resin and may reduce denture stomatitis.

Polymeric Micelles with Uniform Surface Properties and Tunable Size and Charge: Positive Charges Improve Tumor Accumulation.

The influence of surface charge on biodistribution and tumor accumulation remains debatable because most research has been carried out by changing the surface functional groups of nanocarriers. In this work, to avoid the interference of different surface properties such as chemical composition and hydrophilicity, polymeric micelles with uniform PEG coatings and continuously tunable sizes or zeta potentials were developed via a facile route. Therefore, the influence of surface charge on the biological functions of micelles with the same size and surface properties could be well-explored. In this case, positive charge was found to enhance both tumor cellular uptake and tumor accumulation. Immunofluorescence staining indicated that the improved tumor accumulation was mainly due to the tumor vasculature targeting of positively charged micelles. It is predicted that efficient drug delivery systems for both tumor vasculature and cancer cell targeting can be realized based on positively charged micelles.

Nanoscale Plasma Coating Inhibits Formation of Staphylococcus aureus Biofilm.

Staphylococcus aureus commonly infects medical implants or devices, with devastating consequences for the patient. The infection begins with bacterial attachment to the device, followed by bacterial multiplication over the surface of the device, generating an adherent sheet of bacteria known as a biofilm. Biofilms resist antimicrobial therapy and promote persistent infection, making management difficult to futile. Infections might be prevented by engineering the surface of the device to discourage bacterial attachment and multiplication; however, progress in this area has been limited. We have developed a novel nanoscale plasma coating technology to inhibit the formation of Staphylococcus aureus biofilms. We used monomeric trimethylsilane (TMS) and oxygen to coat the surfaces of silicone rubber, a material often used in the fabrication of implantable medical devices. By quantitative and qualitative analysis, the TMS/O2 coating significantly decreased the in vitro formation of S. aureus biofilms; it also significantly decreased in vivo biofilm formation in a mouse model of foreign-body infection. Further analysis demonstrated TMS/O2 coating significantly changed the protein adsorption, which could lead to reduced bacterial adhesion and biofilm formation. These results suggest that TMS/O2 coating can be used to effectively prevent medical implant-related infections.

Polymer-Doxorubicin Conjugate Micelles Based on Poly(ethylene glycol) and Poly(N-(2-hydroxypropyl) methacrylamide): Effect of Negative Charge and Molecular Weight on Biodistribution and Blood Clearance.

Well-defined water-soluble block copolymers poly(ethylene glycol)-b-poly(N-(2-hydroxypropyl) methacrylamide-co-N-methacryloylglycylglycine) (PEG-b-P(HPMA-co-MAGG)) and their doxorubicin (Dox) conjugates with different composition and molecular weight were synthesized. These Dox conjugates can form micelles in buffer solution. The physicochemical properties, in vivo biodistribution, blood clearance, and especially the tumor accumulation of copolymers and micelles were studied. Severe liver accumulation can be observed for PEG-b-PMAGG copolymers. This was quite different from their Dox conjugate for which decreased RES uptake and elevated kidney accumulation could be observed. When decrease the negative charge to an appropriate amount such as 8-10 mol %, both RES uptake and kidney accumulation could be suppressed. Obvious tumor accumulation could be achieved especially when the molecular weight were increased from ∼40 to ∼80 KDa. These results provided us with a guideline for the design of nanoscaled drug delivery system as well as a potential option for treating kidney-related cancers.

Plasma deactivation of oral bacteria seeded on hydroxyapatite disks as tooth enamel analogue.

PURPOSE: To study the plasma treatment effects on deactivation of oral bacteria seeded on a tooth enamel analogue. METHODS: A non-thermal atmospheric pressure argon plasma brush was used to treat two different Gram-positive oral bacteria including Lactobacillus acidophilus (L. acidophilus) and Streptococcus mutans (S. mutans). The bacteria were seeded on hydroxyapatite (HA) disks used as tooth enamel analogue with three initial bacterial seeding concentrations: a low inoculum concentration between 2.1 x 10(8) and 2.4 x 10(8) cfu/mL, a medium inoculum concentration between 9.8x10(8) and 2.4 x 10(9) cfu/mL, and a high inoculum concentration between 1.7 x 10(10) and 3.5 x 10(10) cfu/mL. The bacterial survivability upon plasma exposure was examined in terms of plasma exposure time and oxygen addition into the plasmas. SEM was performed to examine bacterial morphological changes after plasma exposure. RESULTS: The experimental data indicated that a 13-second plasma exposure time completely killed all the bacteria when initial bacterial seeding density on HA surfaces was less than 6.9 x 10(6) cfu/cm2 for L. acidophilus and 1.7 x 10(7) cfu/cm2 for S. mutans, which resulted from low initial seeding inoculum concentration between 2.1 x 10(8) and 2.4 x 10(8) cfu/mL. Plasma exposure of the bacteria at higher initial bacterial seeding density obtained with high initial seeding inoculum concentration, however, only resulted in approximately 1.5 to 2 log reduction and approximately 2 to 2.5 log reduction for L. acidophilus and S. mutans, respectively. It was also noted that oxygen addition into the argon plasma brush did not affect the plasma deactivation effectiveness. SEM images showed that plasma deactivation mainly occurred with the top layer bacteria, while shadowing effects from the resulting bacterial debris reduced the plasma deactivation of the underlying bacteria.

STING Membrane Prevents Post-Surgery Tissue Adhesion and Tumor Recurrence of Colorectal Cancer.

Surgery is the standard treatment regimen for resectable colorectal cancer (CRC). However, it is very hard to completely remove all cancer cells in clinical practice, leading to the high recurrence rates of the disease. Moreover, the post-surgery tissue adhesion greatly prevents the possibility of reoperation, significantly limiting the long-term surviving of CRC patients. To overcome CRC recurrence and avoid the post-surgery tissue adhesion, this work develops a novel stimulator of interferon genes "STING" membrane based on the coaxial electrospinning technology and hyaluronic acid modification. A reactive oxygen species responsive prodrug of gambogic acid (GB) and a potent STING agonist (CDN) are coloaded in the core-shell structure of the membrane, which endows the loaded drug with sustained and sequential release patterns. The localized delivery of GB and CDN can selectively induce efficient immunogenic cell death of cancer cells and then evoke the systemic anticancer immunity by activating the Cyclic GMP-AMP (cGAMP) synthase/STING pathway. As-designed "STING" membrane not only safely prevents tumor recurrence through the synergistic chemoimmunotherapy but also efficiently avoids the post-surgery tissue adhesion, facilitating the clinical intervention of CRC.

Evaluation of plasma treatment effects on improving adhesive-dentin bonding by using the same tooth controls and varying cross-sectional surface areas.

The objective of this study was to evaluate and verify the effectiveness of plasma treatment for improving adhesive-dentin interfacial bonding by performing microtensile bond-strength (µTBS) testing using the same-tooth controls and varying cross-sectional surface areas. Extracted unerupted human third molars were used after removal of the crowns to expose the dentin surface. One half of each dentin surface was treated with a non-thermal argon plasma brush, whilst the other was shielded with glass slide and used as an untreated control. Adper Single Bond Plus adhesive and Filtek Z250 dental composite were then applied as directed. The teeth thus prepared were further cut into micro-bar specimens, with cross-sectional sizes of 1 × 1 mm², 1 × 2 mm², and 1 × 3 mm², for µTBS testing. The test results showed that plasma-treated specimens gave substantially stronger adhesive-dentin bonding than their corresponding same-tooth controls. Compared with their untreated controls, plasma treatment gave statistically significant higher bonding strength for specimens with a cross-sectional area of 1 × 1 mm² and 1 × 2 mm², with mean increases of 30.8% and 45.1%, respectively. Interface examination using optical and electron microscopy verified that plasma treatment improved the quality of the adhesive-dentin interface by reducing defects/voids and increasing the resin tag length in dentin tubules.

Novel strategies for the prevention and treatment of biofilm related infections.

Biofilm formation by human bacterial pathogens on implanted medical devices causes major morbidity and mortality among patients, and leads to billions of dollars in healthcare cost. Biofilm is a complex bacterial community that is highly resistant to antibiotics and human immunity. As a result, novel therapeutic solutions other than the conventional antibiotic therapies are in urgent need. In this review, we will discuss the recent research in discovery of alternative approaches to prevent or treat biofilms. Current anti-biofilm technologies could be divided into two groups. The first group focuses on targeting the biofilm forming process of bacteria based on our understanding of the molecular mechanism of biofilm formation. Small molecules and enzymes have been developed to inhibit or disrupt biofilm formation. Another group of anti-biofilm technologies focuses on modifying the biomaterials used in medical devices to make them resistant to biofilm formation. While these novel anti-biofilm approaches are still in nascent phases of development, efforts devoted to these technologies could eventually lead to anti-biofilm therapies that are superior to the current antibiotic treatment.

Argon Plasma Treatment Effects on the Micro-Shear Bond Strength of Lithium Disilicate with Dental Resin Cements.

The low bond strength of lithium disilicate (LD) ceramics to dental resin cements remains a critical issue for dental applications because it leads to frequent replacement and causes tooth tissue destruction and consumption. The objective of this study was to examine the effects of atmospheric non-thermal argon plasma (NTP) treatment on LD to improve its micro-shear bond strength (µSBS) with dental resin cements because LD mostly experiences shear stress for its commonly used dental applications as crowns or veneers. Argon plasma treatment was performed on hydrofluoric (HF) acid-etched LD surfaces, and then commercial resin cements were subsequently applied to the treated LD surfaces. The plasma treatment significantly reduced the water contact angle of the LD surface to less than 10° without changing the surface morphology. The µSBS test was performed with cement-bonded LD samples after 24 h and 30 days, as well as after 1000 cycles of thermal cycling. The test results show that, as compared with the untreated controls, 300 s of plasma treatment significantly improved the LD-resin cement bond strength by 59.1%. After 30 days of storage in DI water and 1000 cycles of thermal cycling, the plasma-treated LD samples show 84.2% and 44.8% higher bond strengths as compared to the control samples, respectively. The plasma treatment effect on LD surfaces diminished rapidly as the bond strength decreased to 25.5 MPa after aging in the air for 1 day prior to primer and cement application, suggesting that primers should be applied to the LD surfaces immediately after the plasma treatment. These results demonstrate that, when applied with caution, plasma treatment can activate LD surfaces and significantly improve the SBS of LD with dental resin cements in both short-term and long-term periods.

In vitro biological responses of plasma nanocoatings for coronary stent applications.

In-stent restenosis and thrombosis remain to be long-term challenges in coronary stenting procedures. The objective of this study was to evaluate the in vitro biological responses of trimethylsilane (TMS) plasma nanocoatings modified with NH3 /O2 (2:1 molar ratio) plasma post-treatment (TMS + NH3 /O2 nanocoatings) on cobalt chromium (CoCr) alloy L605 coupons, L605 stents, and 316L stainless steel (SS) stents. Surface properties of the plasma nanocoatings with up to 2-year aging time were characterized by wettability assessment and x-ray photoelectron spectroscopy (XPS). It was found that TMS + NH3 /O2 nanocoatings had a surface composition of 41.21 ± 1.06 at% oxygen, 31.90 ± 1.08 at% silicon, and 24.12 ± 1.7 at% carbon, and very small but essential amount of 2.77 ± 0.18 at% nitrogen. Surface chemical stability of the plasma coatings was noted with persistent O/Si atomic ratio of 1.292-1.413 and N/Si atomic ratio of ~0.087 through 2 years. The in vitro biological responses of plasma nanocoatings were studied by evaluating the cell proliferation and migration of porcine coronary artery endothelial cells (PCAECs) and smooth muscle cells (PCASMCs). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay results revealed that, after 7-day incubation, TMS + NH3 /O2 nanocoatings maintained a similar level of PCAEC proliferation while showing a decrease in the viability of PCASMCs by 73 ± 19% as compared with uncoated L605 surfaces. Cell co-culture of PCAECs and PCASMCs results showed that, the cell ratio of PCAEC/PCASMC on TMS + NH3 /O2 nanocoating surfaces was 1.5-fold higher than that on uncoated L605 surfaces, indicating enhanced selectivity for promoting PCAEC growth. Migration test showed comparable PCAEC migration distance for uncoated L605 and TMS + NH3 /O2 nanocoatings. In contrast, PCASMC migration distance was reduced nearly 8.5-fold on TMS + NH3 /O2 nanocoating surfaces as compared to the uncoated L605 surfaces. Platelet adhesion test using porcine whole blood showed lower adhered platelets distribution (by 70 ± 16%), reduced clotting attachment (by 54 ± 12%), and less platelet activation on TMS + NH3 /O2 nanocoating surfaces as compared with the uncoated L605 controls. It was further found that, under shear stress conditions of simulated blood flow, TMS + NH3 /O2 nanocoating significantly inhibited platelet adhesion compared to the uncoated 316L SS stents and TMS nanocoated 316L SS stents. These results indicate that TMS + NH3 /O2 nanocoatings are very promising in preventing both restenosis and thrombosis for coronary stent applications.

Inhibition of Staphylococcus epidermidis biofilm by trimethylsilane plasma coating.

Biofilm formation on implantable medical devices is a major impediment to the treatment of nosocomial infections and promotes local progressive tissue destruction. Staphylococcus epidermidis infections are the leading cause of biofilm formation on indwelling devices. Bacteria in biofilms are highly resistant to antibiotic treatment, which in combination with the increasing prevalence of antibiotic resistance among human pathogens further complicates treatment of biofilm-related device infections. We have developed a novel plasma coating technology. Trimethylsilane (TMS) was used as a monomer to coat the surfaces of 316L stainless steel and grade 5 titanium alloy, which are widely used in implantable medical devices. The results of biofilm assays demonstrated that this TMS coating markedly decreased S. epidermidis biofilm formation by inhibiting the attachment of bacterial cells to the TMS-coated surfaces during the early phase of biofilm development. We also discovered that bacterial cells on the TMS-coated surfaces were more susceptible to antibiotic treatment than their counterparts in biofilms on uncoated surfaces. These findings suggested that TMS coating could result in a surface that is resistant to biofilm development and also in a bacterial community that is more sensitive to antibiotic therapy than typical biofilms.

Plasma SiOx:H Nanocoatings to Enhance the Antibacterial and Anti-Inflammatory Properties of Biomaterials.

PURPOSE: To evaluate the antibacterial and anti-inflammatory properties of SiOx:H nanocoatings using a plasma-deposition technique. MATERIALS AND METHODS: Four groups of SiOx:H nanocoatings were prepared by plasma nanocoating technique using different deposition gases and durations, specifically trimethylsilane (TMS) for groups A1 and A2 and a mixture of TMS and oxygen for groups B1 and B2. Changes in surface chemistry and physical properties were measured. Staphylococcus aureus and Streptococcus mutans were cultured on plasma SiOx:H nanocoatings to evaluate antibacterial and antibiofilm formation activities. Human gingival fibroblasts (HGFs) and HaCaT human keratinocytes were cultured and stimulated with tumor necrosis factor-α (TNF-α). Cell viability was measured using a Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to evaluate anti-inflammatory properties, including the mRNA and protein levels of inflammatory mediators and proinflammatory cytokines. RESULTS: The carbon content was dominant in group A nanocoatings and the oxygen and silicon elements were dominant in group B nanocoatings. Groups A2 and B2 were approximately threefold thicker than groups A1 and B1. The plasma SiOx:H nanocoatings decreased bacterial growth and biofilm formation by 30-70% (p < 0.05). Scanning electron microscopy (SEM) revealed damaged biofilm structures. Moreover, the antibacterial properties of group B were greater than group A, and the antibacterial properties of groups A2 and B2 were more effective than A1 and B1, respectively. CCK-8 assays revealed the plasma SiOx:H nanocoatings had good biocompatibility. Furthermore, under TNF-α-induced inflammation, the mRNA and protein levels of interleukin-6, interleukin-8, cyclooxygenase-2, and monocyte chemoattractant protein-1 were downregulated in the plasma SiOx:H nanocoating groups (p < 0.05). CONCLUSION: Plasma SiOx:H nanocoatings exerted antibacterial and anti-inflammatory effects with excellent biocompatibility. Therefore, the plasma SiOx:H nanocoating technique has potential for implant materials and other medical devices.

Plasma treatment effects on destruction and recovery of Porphyromonas gingivalis biofilms.

The objective of this study was to investigate the treatment effects of non-thermal atmospheric gas plasmas (NTAP) on destruction and the recovery (or re-colonization) of Porphyromonas gingivalis (P. gingivalis) in biofilms. P. gingivalis is a well-known keystone periodontal pathogen strongly associated with periodontal diseases, especially periodontitis. P. gingivalis biofilms were formed on stainless steel coupons and treated for 1, 2, and 5 minutes by NTAP of pure argon gas and argon+oxygen gas mixture. MTT assay, colony forming unit (CFU) counting assay and confocal laser scanning microscopy (CLSM) were used to assess the destruction efficiency. In addition, the plasma treated biofilms were re-cultured in the medium supplemented with antibiotics and oxidative stress sources to determine the synergy of the NTAP with other antimicrobial agents. The results showed the plasma treatment could result in 2.7 log unit reduction in bacterial load. The recovered biofilm CFU with NTAP treatment combined with sub minimal inhibition concentration of amoxicillin was 0.33 log units less than the biofilm treated with amoxicillin alone. The recovered biofilm CFU in NTAP groups was about 2.0 log units less than that in the untreated controls under H2O2 treatment. There was approximately 1.0 log unit reduction of biofilm CFU in plasma treated biofilm compared with untreated control under paraquat treatment. The plasma treated biofilms exhibited less resistance to amoxicillin and greater susceptibility to hydrogen peroxide (H2O2) and paraquat, suggesting that NTAP may enhance biofilm susceptibility to host defense. These in vitro findings suggested that NTAP could be a novel and effective treatment method of oral biofilms that cause periodontal diseases.

Mucus-permeable polymyxin B-hyaluronic acid/ poly (lactic-co-glycolic acid) nanoparticle platform for the nebulized treatment of lung infections.

The aim of this study was to improve the bioavailability of polymyxin B (PMB) in pulmonary nebulized drug delivery. To this end, we developed a nano-delivery system that penetrates the mucus barrier of the lung. Hydrophilic hyaluronic acid (HA) was combined with a water-in-oil system containing a poly (lactic acid)-glycolic acid copolymer of PMB to prepare HA@PLGA-PMB nanoparticles (NPs) with good surface properties. HA@PLGA-PMB NPs with suitable electrical properties, particle size, and good hydrophilicity prevented strong interactions between the NPs and mucus, thereby allowing more drugs to enter deeper into the lung. Compared to the free drug PMB, NPs had more than 2-fold higher mucus penetration efficiency in vitro and better delivery to infected alveolar cells during in vivo nebulization. NPs had better biocompatibility, which further reduced the drug toxicity. More importantly, NPs showed better antimicrobial therapeutic efficacy in the treatment of lung infections in mice. These findings may provide support for the clinical application of nebulized pulmonary antibiotics.