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Herein, we introduce a photobiocidal surface activated by white light. The photobiocidal surface was produced through thermocompressing a mixture of titanium dioxide (TiO 2 ), ultra-high-molecular-weight polyethylene (UHMWPE), and reduced graphene oxide (rGO) powders. A photobiocidal activity was not observed on UHMWPE-TiO 2 . However, UHMWPE-TiO 2 @rGO exhibited potent photobiocidal activity (>3-log reduction) against Staphylococcus epidermidis and Escherichia coli bacteria after a 12 h exposure to white light. The activity was even more potent against the phage phi 6 virus, a SARS-CoV-2 surrogate, with a >5-log reduction after 6 h exposure to white light. Our mechanistic studies showed that the UHMWPE-TiO 2 @rGO was activated only by UV light, which accounts for 0.31% of the light emitted by the white LED lamp, producing reactive oxygen species that are lethal to microbes. This indicates that adding rGO to UHMWPE-TiO 2 triggered intense photobiocidal activity even at shallow UV flux levels.

Polycationic polymers are widely studied antiseptics, and their efficacy is usually quantified by the solution concentration required to kill a fraction of a population of cells (e.g., by Minimum Bactericidal Concentration (MBC)). Here we describe how the response to a polycationic antimicrobial varies greatly among members of even a monoclonal population of bacteria bathed in a single common antimicrobial concentration. We use fluorescence microscopy to measure the adsorption of a labeled cationic polymer, polydiallyldimethylammmonium chloride (PDADMAC, M w ≈ 4 × 10 5 g mol -1 ) and the time course of cell response via a cell permeability indicator for each member of an ensemble of either Escherichia coli, Staphylococcus aureus , or Pseudomonas aeruginosa cells. This is a departure from traditional methods of evaluating synthetic antimicrobials, which typically measure the overall response of a collection of cells at a particular time and therefore do not assess the diversity within a population. Cells typically die after they reach a threshold adsorption of PDADMAC, but not always. There is a substantial time lag of about 5-10 min between adsorption and death, and the time to die of an individual cell is well correlated with the rate of adsorption. The amount adsorbed and the time-to-die differ among species but follow a trend of more adsorption on more negatively charged species, as expected for a cationic polymer. The study of individual cells via time-lapse microscopy reveals additional details that are lost when measuring ensemble properties at a particular time.

Introduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus ( S. aureus ), a prominent pathogen responsible for hospital-acquired infections., Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV-Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus -preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied., Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC 50 for MRSA biofilm = 0.029 nM; MBEC 50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC 50 for MRSA biofilm = 10,784 nM; MBEC 50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 µM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy., Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms., Competing Interests: Dr Sek Peng Chin reports a patent UI 2022007566, Malaysian Utility Innovation pending. Professor Lik Voon Kiew reports a patent UI 2022007566 pending. The authors report no other conflicts of interest in this work., (© 2024 Manimaran et al.)

Background: Skin fibrosis affects the normal function of the skin. TGF-β1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-β1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-β1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE., Methods: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-β1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics., Results: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis., Conclusion: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis., (© 2024. The Author(s).)

The occurrence of periprosthetic joint infections (PJI) after total joint replacement constitutes a great burden for the patients and the healthcare system. Antibiotic-loaded polymethylmethacrylate (PMMA) bone cement is often used in temporary spacers during antibiotic treatment. PMMA is not a load-bearing solution and needs to be replaced by a functional implant. Elution from the ultrahigh molecular weight polyethylene (UHMWPE) bearing surface for drug delivery can combine functionality with the release of clinically relevant doses of antibiotics. In this study, the feasibility of incorporating a range of antibiotics into UHMWPE is investigated. Drug stability is assessed by thermo-gravimetric analysis and nuclear magnetic resonance spectroscopy. Drug-loaded UHMWPEs are prepared by compression molding, using eight antibiotics at different loading. The predicted intra-articular concentrations of drugs eluted from UHMWPE are above minimum inhibitory concentration for at least 3 weeks against Staphylococci, which are the major causative bacteria for PJI. The antibacterial efficacy is confirmed for samples covering 2% of a representative knee implant in vitro over 72 h, showing that a small fraction of the implant surface loaded with antibiotics may be sufficient against Staphylococci., (© 2023 The Authors. Macromolecular Bioscience published by Wiley‐VCH GmbH.)

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. There are no effective therapies available for TBI patients. Vepoloxamer is an amphiphilic polyethylene-polypropylene-polyethylene tri-block copolymer that seals membranes and restores plasma membrane integrity in damaged cells. We previously demonstrated that treatment of TBI rats with Vepoloxamer improves functional recovery. However, additional studies are needed to potentially translate Vepoloxamer treatment from preclinical studies into clinical applications. We thus conducted a study to investigate dose-response and therapeutic window of Vepoloxamer on functional recovery of adult rats after TBI. To identify the most effective dose of Vepoloxamer, male Wistar adult rats with controlled cortical impact (CCI) injury were randomly treated with 0 (vehicle), 100, 300, or 600 mg/kg of Vepoloxamer, administered intravenously (IV) at 2 h after TBI. We then performed a therapeutic window study in which the rats were treated IV with the most effective single dose of Vepoloxamer at different time points of 2 h, 4 h, 1 day, or 3 days after TBI. A battery of cognitive and neurological tests was performed. Animals were killed 35 days after TBI for histopathological analysis. Dose-response experiments showed that Vepoloxamer at all three tested doses (100, 300, 600 mg/kg) administered 2 h post injury significantly improved cognitive functional recovery, whereas Vepoloxamer at doses of 300 and 600 mg/kg, but not the 100 mg/kg dose, significantly reduced lesion volume compared to saline treatment. However, Vepoloxamer at 300 mg/kg showed significantly improved neurological and cognitive outcomes than treatment with a dose of 600 mg/kg. In addition, our data demonstrated that the dose of 300 mg/kg of Vepoloxamer administered at 2 h, 4 h, 1 day, or 3 days post injury significantly improved neurological function compared with vehicle, whereas Vepoloxamer administered at 2 h or 4 h post injury significantly improved cognitive function compared with the 1-day and 3-day treatments, with the most robust effect administered at 2 h post injury. The present study demonstrated that Vepoloxamer improves functional recovery in a dose-and time-dependent manner, with therapeutic efficacy compared with vehicle evident even when the treatment is initiated 3 days post TBI in the rat., Competing Interests: Declaration of competing interest Marty Emanuele was an employee of LifeRaft Technologies, Inc., San Diego, CA. and currently he is an employee of Visgenx, Inc., Santa Cruz, CA. For the other authors, no competing financial interests exist., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Owing to its antimicrobial activity, electrochemically activated water (ECAW) is a potential alternative to chemical disinfectants for eliminating foodborne pathogens, including Salmonella Heidelberg, from food processing facilities. However, their antibiofilm activity remains unclear. This study aimed to evaluate the antibiofilm activity of ECAW against S. Heidelberg biofilms formed on stainless steel and polyethylene and to determine its corrosive capacity. ECAW (200 ppm) and a broad-spectrum disinfectant (0.2%) were tested for their antibiofilm activity against S. Heidelberg at 25 °C and 37 °C after 10 and 20 min of contact with stainless steel and polyethylene. Potentiostatic polarization tests were performed to compare the corrosive capacity of both compounds. Both compounds were effective in removing S. Heidelberg biofilms. Bacterial counts were significantly lower with ECAW than with disinfectant in polyethylene, regardless the time of contact. The time of contact and the surface significantly influenced the bacterial counts of S. Heidelberg. Temperature was not an important factor affecting the antibiofilm activities of the compounds. ECAW was less corrosive than the disinfectant. ECAW demonstrated a similar or even superior effect in the control of S. Heidelberg biofilms, when compared to disinfectants, reducing bacterial counts by up to 5 log 10 CFU cm -2 . The corrosion of stainless steel with ECAW was similar to that of commercial disinfectants. This technology is a possible alternative for controlling S. Heidelberg in the food production chain., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Pluronic F127 hydrogel biomaterial has garnered considerable attention in wound healing and repair due to its remarkable properties including temperature sensitivity, injectability, biodegradability, and maintain a moist wound environment. This comprehensive review provides an in-depth exploration of the recent advancements in Pluronic F127-derived hydrogels, such as F127-CHO, F127-NH 2 , and F127-DA, focusing on their applications in the treatment of various types of wounds, ranging from burns and acute wounds to infected wounds, diabetic wounds, cutaneous tumor wounds, and uterine scars. Furthermore, the review meticulously examines the intricate interaction mechanisms employed by these hydrogels within the wound microenvironment. By elucidating the underlying mechanisms, discussing the strengths and weaknesses of Pluronic F127, analyzing the current state of wound healing development, and expanding on the trend of targeting mitochondria and cells with F127 as a nanomaterial. The review enhances our understanding of the therapeutic effects of these hydrogels aims to foster the development of effective and safe wound-healing modalities. The valuable insights provided this review have the potential to inspire novel ideas for clinical treatment and facilitate the advancement of innovative wound management approaches., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Li et al.)

Medical plastics such as those found in endotracheal tubes are widely used in intensive care units for the treatment of critically ill patients. Although commonplace in hospital environment, these catheters are at a high risk of bacterial contamination and have been found responsible for numerous health-care-associated infections. Antimicrobial coatings that can prevent harmful bacterial growth are required to reduce the occurrence of such infections. In this study, we introduce a facile surface treatment strategy that could form antimicrobial coatings on the surface of average medical plastics. The strategy involves treatment of activated surfaces with lysozyme, a natural antimicrobial enzyme presenting in human lacrimal gland secretions which is widely used for wound healing. Using ultra-high molecular weight polyethylene (UHMWPE) as the representative surface, oxygen/argon plasma treatment for 3 min led to the increase of surface roughness and the generation of negatively charged groups, with the zeta potential measured as -94.5 mV at pH 7. The activated surface could accommodate lysozyme with a density of up to 0.3 nmol/cm 2 through electrostatic interaction. Antimicrobial activity of the resulting surface (UHMWPE@Lyz) was characterized with Escherichia coli and Pseudomonas sp. strains, and the treated surface significantly inhibited the bacterial colonization and the formation of biofilm compared to the untreated UHMWPE. This method of constructing an effective lysozyme-based antimicrobial coating is a generally applicable, simple and fast process for surface treatment with no adverse solvent and wastes involved., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Total joint arthroplasty is one of the most common surgeries in the United States, with almost a million procedures performed annually. Periprosthetic joint infections (PJI) remain the most devastating complications associated with total joint replacement. Effective antibacterial prophylaxis after primary arthroplasty could substantially reduce incidence rate of PJI. In the present study we propose to provide post-arthroplasty prophylaxis via dual-analgesic loaded ultra-high molecular weight polyethylene (UHMWPE). Our approach is based on previous studies that showed pronounced antibacterial activity of analgesic- and NSAID-loaded UHMWPE against Staphylococci. Here, we prepared bupivacaine/tolfenamic acid-loaded UHMWPE and assessed its antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. Dual-drug loaded UHMWPE yielded an additional 1-2 log reduction of bacteria, when compared with single-drug loaded UHMWPE. Analysis of the drug elution kinetics suggested that the observed increase in antibacterial activity is due to the increased tolfenamic acid elution from dual-drug loaded UHMWPE. We showed that the increased fractal dimension of the drug domains in UHMWPE could be associated with increased drug elution, leading to higher antibacterial activity. Dual-analgesic loaded UHMWPE proposed here can be used as part of multi-modal antibacterial prophylaxis and promises substantial reduction in post-arthroplasty mortality and morbidity., (© 2022 Wiley Periodicals LLC.)

Vanillic acid incorporated chitosan/poly(vinyl alcohol) active films were prepared by employing a cost-effective solvent casting technique. FTIR investigation validated the intermolecular interaction and formation of Schiff's base (C=N) between functional groups of vanillic acid, chitosan, and poly(vinyl alcohol). The addition of vanillic acid resulted in homogenous and dense morphology, as confirmed by SEM micrographs. The tensile strength of active films increased from 32 to 59 MPa as the amount of vanillic acid increased and the obtained values are more significant than reported polyethylene (2231 MPa) and polypropylene (31-38 MPa) films, widely utilized in food packaging. Active film's UV, water, and oxygen barrier properties exhibited excellent results with the incorporation of vanillic acid. Around 40 % of degradation commences within 15 days. Synergistic impact against S. aureus, E. coli, and C. albicans pathogens caused the expansion of the inhibition zone, evidenced by the excellent antimicrobial activity. The highest antioxidant capacity, 73.65 % of CPV-4 active film, proved that active films could prevent the spoilage of food from oxidation. Green chillies packaging was carried out to examine the potential of prepared active films as packaging material results in successfully sustaining carotenoid accumulation and prolonging the shelf life compared to conventional polyethylene (PE) packaging., Competing Interests: Declaration of competing interest, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Wear particles of ultra-high molecular weight polyethylene (UHMWPE) are inevitable during service as joint prosthesis, and particles ≤ 10 μm with critical size could cause serious osteolysis and aseptic loosening of joint prosthesis. The aim of this study is to adopt the alginate-encapsulated cell reactor to investigate the molecular impact of critical-sized wear particles of UHMWPE loaded with alendronate sodium (UHMWPE-ALN) on cells. Results showed that compared with UHMWPE wear particles, UHMWPE-ALN wear particles inhibited the proliferation of macrophages significantly after being co-cultured for 1, 4, 7, and 14 d. Furthermore, the released ALN promoted early apoptosis, suppressed the secretion of TNF-α and IL-6 of macrophages, and down-regulated relative gene expressions of TNF-α, IL-6, and IL-1β and RANK. In addition, compared with UHMWPE wear particles, UHMWPE-ALN wear particles promoted the ALP activity of osteoblasts, down-regulated the gene expression of RANKL, and up-regulated gene expression of osteoprotegerin. There were mainly two approaches of the effects of critical-sized UHMWPE-ALN wear particles on cells, one of which was cytology and the other was cytokine signal pathway. The former mainly affected the proliferation and activity of macrophages and osteoblasts. The latter would inhibit osteoclasts via cytokine and RANKL/RANK signal pathway. Thus, UHMWPE-ALN had the potential application in clinics to treat osteolysis induced by wear particles.

Microplastic pollution is currently one of the most intensely studied ecological issues. Numerous studies have estimated the distribution and concentration of microplastics in various environments and determine how they affect their inhabitants. Much less effort has been place on assessing the possible effects of microplastics on interactions between organisms, including interspecific competition. Our aim was to test the hypothesis that the presence of microplastics affects the proportion of individuals of coexisting species and the elimination rate of the inferior competitor. The hypothesis was tested in competitive experiments done in the absence and presence of spherical non-biodegradable polystyrene and polyethylene and biodegradable polyhydroxybutyrate in environmentally relevant densities. In each of the experiments, we used three different pairs of closely related planktonic species of the genus Daphnia composed of the superior and inferior competitor: D. pulex and D. magna, D. magna and D. galeata, D. pulex and D. galeata. The results support our hypothesis and demonstrate each microplastic type had a different effect on the density of the competing species. The presence of polystyrene and polyethylene lowered the density of the superior competitor in each of the three pairs, at least partially due to a reduction in the number of gravid females, but not their fecundity. The presence of the polyhydroxybutyrate, in turn, increased the population density of D. magna in the variants with each of the two remaining species. Moreover, the presence of microplastics affected the elimination rate of the inferior competitor, i.e. polystyrene expedited the exclusion of D. magna by D. pulex, and polyhydroxybutyrate hampered the exclusion of D. magna by D. pulex. Our results suggest that long-term exposure to environmentally relevant densities of both non-biodegradable and biodegradable microplastics may affect the relative abundance of co-occurring species in zooplankton communities, and thus the functioning of aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Piotr Maszczyk reports financial support was provided by Polish National Science Centre. Ewa Babkiewicz reports financial support was provided by Polish National Science Centre., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Natural substances such as omega-3 have been used in the medical field due to their numerous properties and, in particular, modulating effect on the systemic and local inflammatory processes. Thus, this study evaluated the influence of omega-3 supplementation on the subcutaneous tissue response of endodontic sealers in Wistar Rats., Methodology: Polyethylene tubes were implanted in the subcutaneous tissue of 48 animals (one empty for control and three filled with Sealapex, AH Plus or Endofill). The animals were treated with omega-3 (TO) or water (TW). Treatments started 15 days before implantation until euthanasia. After 5, 15 and 30 days (n = 8), animals were euthanized and polyethylene tubes and surrounding tissue were removed and processed for histological analysis. The inflammatory reaction was analysed by Haematoxylin and Eosin stain and immunolabelling for IL-6 and TNF-α. The collagen maturity was analysed by picrosirius red stain and calcium deposition by von Kossa stain and polarized light. Results were statistically analysed (p < .05)., Results: Amongst TW sealer groups, Endofill evoked a more intense inflammatory infiltrate compared with AH Plus and control in the 30-day period (p = .009). However, in TO sealer groups, there was no difference amongst the sealers and control in all periods (p > .05). Comparing each sealer as a function of the supplementation with water or omega-3, there are differences for Endofill (p = .001) and Sealapex (p = .005) in the 30-day period, presenting lower inflammatory infiltrate in the animals treated with omega-3. A higher percentage of immature fibres was observed at 15 and 30 days in the TO group, compared with the TW group (p < .05). The deposition of calcium particles was observed only by Sealapex in all periods, despite the supplementation procedure., Conclusions: Omega-3 supplementation influence the tissue reactions of endodontic sealers, modulating inflammation, the immunolabelling of IL-6 and TNF-α, the repair process and it does not interfere with calcium deposition., (© 2022 British Endodontic Society. Published by John Wiley & Sons Ltd.)

Microbial adhesion and contamination on shared surfaces can lead to life-threatening infections with serious impacts on public health, economy, and clinical practices. The traditional use of chemical disinfectants for sanitization of surfaces, however, comes with its share of health risks, such as hazardous effects on the eyes, skin, and respiratory tract, carcinogenicity, as well as environmental toxicity. To address this, we have developed a nonleaching quaternary small molecule (QSM)-based sprayable coating which can be fabricated on a wide range of surfaces such as nylon, polyethylene, surgical mask, paper, acrylate, and rubber in a one-step, photocuring technique. This contact-active coating killed pathogenic bacteria and fungi including drug-resistant strains of Staphylococcus aureus and Candida albicans within 15-30 min of contact. QSM coatings withstood multiple washes, highlighting their durability. Interestingly, the coated surfaces exhibited rapid killing of pathogens, leading to the prevention of their transmission upon contact. The coating showed membrane disruption of bacterial cells in fluorescence and electron microscopic investigations. Along with bacteria and fungi, QSM-coated surfaces also showed the complete killing of high loads of influenza (H1N1) and SARS-CoV-2 viruses within 30 min of exposure. To our knowledge, this is the first report of a coating for multipurpose materials applied in high-touch public places, hospital equipment, and clinical consumables, rapidly killing drug-resistant bacteria, fungi, influenza virus, and SARS-CoV-2.

The introduction of vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) for use in prosthetic components of hip implants has resulted in the production of implants that have excellent mechanical properties and substantially less adverse cellular responses. Given the importance of a biological response to wear in the survival of a prosthesis, we generated wear debris from UHMWPE that had been prepared with different concentrations of vitamin E of 0.1, 0.3, 0.5, and 1% and evaluated their biological reaction in vitro and in vivo. All types of VE-UHMWPE debris promoted a significantly lower expression of Tnf-α in murine peritoneal macrophages than that induced by conventional UHMWPE debris. However, levels of Tnf-α were not significantly different among the macrophages that were stimulated with VE-UHMWPE wear at the concentrations tested. The ability of wear debris to induce inflammatory osteolysis was assessed in a mouse calvarial osteolysis model. The expressions of Tnf-α, Il-6, and Rankl in granulomatous tissue formed around the wear debris were significantly reduced in mice that had been implanted with 0.3%VE-UHMWPE debris as compared to the corresponding values for mice that had been implanted with UHMWPE debris. Consistent with this finding, 0.3%VE-UHMWPE debris showed the lowest osteolytic activity, as evidenced by the reduced bone resorption area, the degree of infiltration of inflammatory cells and the TRAP staining area. Our results suggested that a 0.3% vitamin E concentration is the most appropriate concentration for use in prosthetic components with a reduced adverse cellular response for prolonging the life-span of the implant., (© 2022 Wiley Periodicals LLC.)

Two synthetic approaches were explored for modification of the polyolefins polyethylene/polypropylene (PE/PP) to form contact-active nonwoven materials. In the first approach, polymer surfaces were activated by O 2 -free air-ozonolysis, and then the active agent (trimethoxysilyl) propyl-octadecyl-dimethyl-ammonium chloride (C18-TSA) was covalently bound. In the second approach, the active agent was directly conjugated to the commercial 'finishing' that was then applied to the polymer. The chemical, physical and microscopic properties of the modified polymers were comprehensively studied, and their active site density was quantified by fluorescein sodium salt-cetyltrimethylammonium chloride reaction. The antimicrobial activity of the prepared nonwovens against Bacillus subtilis (Gram-positive) and Salmonella enterica (Gram-negative), and their stability at various pHs and temperatures were examined. The two approaches conferred antimicrobial properties to the modified polymers and demonstrated stable linkage of C18-TSA. However, the performance of the nonwovens formed by the first approach was superior. The study suggests two feasible and safe pathways for the modification of polyolefins to form contact-active nonwoven materials that can be further applied in various fields, such as hygiene products, medical fabrics, sanitizing wipes, and more.

Recently, nanoparticles have been widely used in drug and vaccine adjuvant delivery. Dendrobium devonianum Polygonatum (DP), a main biologically active ingredient isolated from Dendrobium devonianum, has been widely used in the clinic as an immunostimulant to stimulate and improve immune responses, contributing to its excellent biological activity. To increase the immune efficacy of DP, macrophage cell membrane-coated drug nanocrystals featuring homologous immune escape, targeting ability and low toxicity are in high demand. In this study, a new drug and vaccine adjuvant delivery system, PEI-MM-PLGA-DP/OVA, was designed and developed. This study aimed to report the macrophage immunomodulatory activity of PEI-modified macrophage cell membrane-coated PLGA nanoparticles encapsulating Dendrobium devonianum polysaccharides. PEI-MM-PLGA-DP/OVA could promote antigen uptake by macrophage and lymphocyte proliferation, increase the expression levels of MHC II, CD80 and CD86, and upregulate the ratio of CD4 + to CD8 + T cells in immunized mice. PEI-MM-PLGA-DP/OVA induced the highest TNF-α, IFN-γ, IL-4, and IL-6 cytokine secretion levels and the levels of OVA-specific antibodies (IgG) compared with the other groups. The above results indicated that PEI-MM-PLGA-DP/OVA had better adjuvant activity than PLGA-DP/OVA and MM-PLGA-DP/OVA., (Copyright © 2020. Published by Elsevier B.V.)

Periprosthetic joint infection (PJI) is one of the main causes for the failure of joint arthroplasty. In view of the limited clinical effect of oral/injectable antibiotics and the drug resistance problem, there is a pressing need to develop antibacterial implants with therapeutic antimicrobial properties. In this work, we prepared a highly antibacterial ultrahigh molecular weight polyethylene (UHMWPE) implant by incorporating tea polyphenols. The presence of tea polyphenols not only improved the oxidation stability of irradiated UHMWPE, but also gave it the desirable antibacterial property. The potent antibacterial activity was attributed to the tea polyphenols that produced excess intracellular reactive oxygen species and destroyed the bacterial membrane structure. The tea polyphenol-blended UHMWPE had no biological toxicity to human adipose-derived stem cells and effectively reduced bacteria-induced inflammation in vivo. These results indicate that tea polyphenol-blended UHMWPE is promising for joint replacement prostheses with multifunctionality to meet patient satisfaction.

Background and purpose - Survivorship of total hip arthroplasty (THA) with the ultra-high molecular weight polyethylene (UHMWPE) monoblock cup has been limited due to periprosthetic osteolysis and aseptic loosening, secondary to wear of the UHMWPE. In response, a vitamin E blended highly cross-linked polyethylene (HXLPE) cup was developed. This study set out to compare the wear and clinical 6-year outcomes of vitamin E blended HXLPE with UHMWPE in an isoelastic monoblock cup in patients with hip osteoarthritis who underwent uncemented THA. The 2-year results have been reported previously. Patients and methods - For this randomized controlled trial 199 patients were included. 102 patients received the vitamin E blended HXLPE uncemented acetabular cup and 97 patients the uncemented UHMWPE monoblock cup. Clinical and radiographic parameters were obtained preoperatively, directly postoperatively, and at 3, 12, 24, and 72 months. Wear rates were compared using the femoral head penetration (FHP) rate. Results - 173 patients (87%) completed the 6-year follow-up. The mean NRS scores for rest pain, load pain, and patient satisfaction were 0.3 (SD 1), 0.6 (SD 1), and 8.6 (SD 1) respectively. The mean Harris Hip Score was 93 (SD 12). The FHP rate was lower in the vitamin E blended HXLPE cup (0.028 mm/year) compared with the UHMWPE cup (0.035 mm/year) (p = 0.002). No adverse reactions associated with the clinical application of vitamin E blended HXLPE were observed. 15 complications occurred, equally distributed between the two cups. The 6-year survival to revision rate was 98% for both cups. There was no aseptic loosening. Interpretation - This study shows the superior performance of the HXLPE blended with vitamin E acetabular cup with clinical and radiographic results similar to the UHMWPE acetabular cup.

Infectious diseases induced by pathogenic bacteria are the major causes for the failure of medical implants. Meanwhile, the drug-resistance is steadily developed because of the large and even inappropriate use of antibiotics. Therefore, the development of antibacterial coating with non-antibiotic-based agents on the surfaces of medical implants and devices has been an urgent need. Herein, we propose a bottlebrush-like antibacterial coating on a poly(styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS) triblock copolymer surface by UV-induced graft polymerization of poly(ethylene glycol) (PEG) acrylate terminated poly(lysine dendrimer). This PEG-conjugated antibacterial polymer possessed a substructure of α-helical backbone and cation dendrimer side chains stretching in the radial directions of the helix. The introduction of lysine peptide dendrimers endowed the prepared antibacterial polymer with precisely controlled characteristics of its local cation density, amphipathic composition as well as three-dimensional (3D) conformation to improve interactions with bacterial membranes. The antimicrobial assay and biocompatibility assay results showed that 96.83% of S. aureus and 99.99% of E. coli were killed after being in contact with the antibacterial coating, while no toxicity to mammalian cells or no hemolysis was detected. This antimicrobial activity was further confirmed by the molecular dynamics simulation results, which demonstrated that the employment of lysine peptide dendrimers enhanced the electrostatic interaction and hydrogen bonding between the brush and bacterial membranes remarkably. Such bottlebrush-like antibacterial coating constructed using α-helical peptide dendritic polymers may become an effective strategy for manufacturing antibacterial products for biomedical uses.

Objective: To investigate the role of miR-411-5p and miR-434-3p in osteoblast differentiation in particulate-induced osteolysis., Methods: A mouse model of osteolysis and an in vitro osteolysis model were constructed. The expressions of molecules were detected using qRT-PCR and western blot. Alkaline phosphatase (ALP) activity was measured using the ALP Assay Kit, and the bone mineralization was measured using alizarin red staining., Results: The expression of miR-411-5p and miR-434-3p was decreased in osteolysis mice and UHMWPE-induced mMSCs, while GATA4 protein expression was increased. Over-expression of miR-411-5p and miR-434-3p up-regulated the expressions of osteoblast gene markers, enhanced the ALP activity, promoted the bone mineralization of mesenchymal stem cells. In addition, miR-411-5p and miR-434-3p could target GATA4, and miR-411-5p/434-3p affected the expressions of osteoblast gene markers through GATA4 in vitro and in vivo., Conclusion: Overexpression of miR-411-5p and miR-434-3p promoted the osteoblast differentiation by inhibiting GATA4 expression., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest in this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Triptolide, an ingredient of Tripterygium wilfordii, has been demonstrated to possess many biological activities such as immunomodulatory, antitumor activity in experiment. The purpose of this study was to survey the toxicity of TPL-PEI-CyD on renal cells and its effects on breast carcinoma stem cells. The cytotoxicity of TPL-PEI-CyD and TPL on HK-2 was comparatively assessed by CCK-8. After incubation and culturing with TGF-β1, the MCF-7 cells were assessed by flow cytometry for the proportion of CD 44 +> CD 24 - cells; then the CD 44 > +> CD 24 - cells were sorted by immunomagnetic beads as MCF-7 stem cells. To assess the effect of TPL-PEI-CyD on MCF-7 stem cells, Western Blot was used to detect the expression of Oct-4 and ALDHl in MCF-7 stem cells after being dosed with TPL- PEI-CyD. Results showed that, compared with TPL, the toxicity of TPL-PEI-CyD on HK-2 cells was significantly reduced (P<0.05). Breast carcinoma stem cells can be enriched by TGF-β1 and isolated from MCF-7 cells by immunomagnetic sorting. TPL- PEI-CyD can even more significantly suppress the expression of Oct-4 and ALDHA1 in MCF-7 stem cells than TPL (P<0.05). In conclusion, after coupling TPL and PEI-CyD, TPL-PEI-CyD showed characteristics of effective suppression to breast carcinoma stem cell and decrease of cytotoxicity. It presented the unique effect of traditional Chinese medicine as an efficient and low toxic drug carrier complex for breast carcinoma treatment.

In order to further enhance hydrophilicity of zein and achieve nano-scale pesticide system, phosphorylated zein (P-Zein) was incorporated with graft copolymer CMC-g-PDMDAAC by electrostatic interaction, in which carboxymethyl cellulose (CMC) and diallyldimethylammonium chloride (DMDAAC) as monomers. P-Zein/CMC-g-PDMDAAC was applied to encapsulate model pesticide avermectin (AVM) via electrostatic interaction to achieve AVM@P-Zein/CMC-g-PDMDAAC nano-pesticides. The stability, drug loading, anti-ultraviolet, adhesion, sustained-release and toxicity of nano-pesticides presented considerable behavior confirmed via various characteristics. The results indicated that AVM@P-Zein/CMC-g-PDMDAAC had an average particle size of 360 nm, and possessed favorable dispersion performance and excellent anti-ultraviolet property compared to P-Zein. And comparatively, encapsulation efficiency increased up to 82.11%. In addition, adhesion performance of AVM@P-Zein/CMC-g-PDMDAAC on foliage also improved by about 20% compared to P-Zein. Also, AVM@P-Zein/CMC-g-PDMDAAC can intelligently control pesticide release by adjusting monomer ratio and pH values. More importantly, such nano-pesticide system presented no significant difference on toxicity in comparison with bare AVM., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ultra-High Molecular Weight Polyethylene (UHMWPE) is the gold standard biomaterial used as a bearing surface in total joint replacement surgeries. However, osteolysis and subsequent implant failure as a result of the production of wear debris may occur at the contacting surfaces. One potential solution to overcome this problem is to strengthen the surface of UHMWPE which can be achieved by adding a thin coating layer made of Polyamide. In this article, a combination of biological and biochemical tests, including cell viability, antibacterial activity (using Escherichia coli and Staphylococcus aureus), and wound healing assays were performed to assess the bioactivity and the biocompatibility of the coated specimens. Additional tests, such as simulated body fluid absorption, Alizarin Red Staining, Scanning Electron Microscopy, Energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy techniques were conducted to evaluate the moisture uptake, osteogenic activity, and the morphology of the coated samples. The antibacterial activity test results after 24 h incubation showed that the nylon-coated UHMWPE has significantly higher antibacterial activity compared to the uncoated UHMWPE. The results of wound closure showed that nylon-coated UHMWPE promotes more wound healing compared to the uncoated material that exhibits a similar percentage of wound closure as the control. This is the first study to demonstrate the superiority of the proposed coated biomaterial for wound healing applications with improved antibacterial capabilities., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The artificial joints, for example, knee and hip implants, are widely used for the treatment of degenerative joint diseases and trauma. The current most common material choice for clinically used implants is the combination of polymer-on-metal structures. Unfortunately, these joints often suffer from high friction and wear, leading to associated inflammation and infection and ultimate failure of the artificial joints. Here, we propose an alternative solution to this tribologically induced failure of the joint materials. We demonstrate that the friction and wear behavior of ultrahigh-molecular-weight polyethylene (UHMWPE) and titanium tribopair, used to mimic the artificial joint interface, can be improved by introducing nanodiamond (ND) particles in the sliding contact. Characterization of the wear track using energy-dispersive spectroscopy and Raman spectroscopy revealed that the tribofilm formed from embedded NDs during sliding significantly suppressed the wear of the UHMWPE surface. In addition to the improved lubrication characteristics, NDs exhibit high biocompatibility with the bone cells and promising antibacterial properties against Staphylococcus aureus , the most common strain associated with artificial joint infection. These results indicate that NDs can be used as a promising nontoxic human-body lubricant with antiwear and antibacterial features, thus demonstrating their great potential to treat artificial joint complications through intra-articular injection.

Hypoxia and overexpression of glutathione (GSH) are typical characteristics of the tumor microenvironment, which severely hinders cancer treatments. Here, we design a novel biodegradable therapeutic system, O 2 -Cu/ZIF-8@Ce6/ZIF-8@F127 (OCZCF), to simultaneously achieve GSH depletion and O 2 -enhanced combination therapy. Notably, the doped Cu 2+ doubles the O 2 storage capacity of the ZIF-8 matrix, which makes OCZCF an excellent pH-sensitive O 2 reservoir for conquering tumor hypoxia, enhancing the photodynamic therapy (PDT) efficiency of chlorin e6 (Ce6) under 650 nm laser irradiation. Moreover, the released Cu 2+ can act as a smart reactive oxygen species protector by consuming intracellular GSH. The byproduct Cu + will undergo highly efficient Fenton-like reaction to achieve chemodynamic therapy (CDT) in the presence of abundant H 2 O 2 . The accompanying O 2 will further alleviate hypoxia. The in vitro and in vivo experimental data indicate that OCZCF could cause remarkable tumor inhibition through enhanced synergetic PDT and CDT, which may open up a new path for cancer therapy.

Chemical cross-linking of ultrahigh molecular weight polyethylene (UHMWPE) using an organic peroxide followed by high temperature melting results in a large increase in toughness accompanied by a decrease in cross-link density, which, surprisingly does not compromise the wear resistance. We compared the mechanical properties and wear behavior of a vitamin E blended, chemically cross-linked and high temperature melted UHMWPE produced by ram extrusion (PRX HTM) to those measured with the clinically available 100-kGy irradiated and melted UHMWPE (CISM 100). We also assessed the local biocompatibility of PRX-HTM in rabbit subcutaneous pouch and osteochondral defect models. The ultimate tensile strength and pin-on-disc wear rate were similar to CISM 100; whereas the elongation-at-break and impact toughness were much higher with PRX-HTM. The stress intensity factor range at crack inception was also higher with PRX-HTM. Accelerated aging did not result in any measurable oxidation or changes in mechanical properties. Hip simulator wear rate of acetabular liners made with PRX-HTM was 0.3 ± 0.4 mg/million-cycle, similar to that reported for CISM 100 liners. The wear particles were largely spherical with a number-averaged particle size of 0.95 μm with ~75% of particles below 1 μm. The subcutaneous and osteochondral rabbit implantations showed no histological differences between PRX-HTM and the control CISM 100. Pre-clinical wear, mechanical, and biocompatibility testing of PRX HTM showed feasibility for the use of this material as a total joint arthroplasty implant bearing surface. This process has the potential of eliminating the additional step of radiation cross-linking by combining consolidation and cross-linking while improving toughness. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1945-1952, 2019., (© 2018 Wiley Periodicals, Inc.)

Highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) was introduced to decrease wear debris and osteolysis. During cross-linking, free radicals are formed, making highly cross-linked polyethylene vulnerable to oxidative degradation. In order to reduce this process, anti-oxidant vitamin E can be incorporated in polyethylene. This review provides an overview of the effects of vitamin E incorporation on major complications in total joint arthroplasty: material failure due to oxidative degradation, wear debris and subsequent periprosthetic osteolysis, and prosthetic joint infections. Secondly, this review summarizes the first clinical results of total hip and knee arthroplasties with vitamin E incorporated highly cross-linked polyethylene. Based on in vitro studies, incorporation of vitamin E in polyethylene provides good oxidative protection and preserves low wear rates. Incorporation of vitamin E may have the beneficial effect of reduced inflammatory response to its wear particles. Some microorganisms showed reduced adherence to vitamin E-incorporated UHMWPE; however, clinical relevance is doubtful. Short-term clinical studies of total hip and knee arthroplasties with vitamin E-incorporated highly cross-linked UHMWPE reported good clinical results and wear rates similar to highly cross-linked UHMWPE without vitamin E.

Introduction: Acrylic resins are used in the preparation of facial prostheses and may be colonized by fungi. Here, we verified the antifungal efficacy of this material after surface treatment using poly (diallyldimethylammonium chloride)., Methods: Acrylic resin specimens with and without surface treatment were subjected to tests for fungistatic and fungicidal activities. Standard strains of Candida albicans and Aspergillus niger were used., Results: After surface treatment, the fungistatic and fungicidal efficacies of the resins against C. albicans and fungistatic action against A. niger were verified., Conclusions: The surface treatment was a determinant of the antifungal activity of the material.

We report here for the first time how the combination of a precursor solution and low temperature (170 °C) aerosol assisted chemical vapour deposition were used to bond a copper coating to ultra-high molecular weight polyethylene (UHMWPE) and promote robustness. This metallic thin film remained intact on the UHMWPE substrate after the Scotch tape test and showed notable wear-resistance after 10 cycles of sand paper-abrasion. Antimicrobial assays against both Escherichia coli and Staphylococcus aureus revealed potent dark bactericidal activity with 99.999% reduction in bacterial number within 15 minutes. These results suggest that the modified UHMWPE could be a potential candidate for antimicrobial plastics and in the long term may find application in prosthetic joint applications.

Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly introduced material for prosthetic components that has proven a better mechanical performance with lesser adverse cellular responses than conventional polyethylene in experimental animal models. However, the mechanisms by which VE-UHMWPE particles trigger a reduced osteolytic activity are unclear and remain to be investigated. Therefore, the current study aims at exploring a possible anti-osteolytic mechanism associated with VE-UHMWPE particles. Transcriptional profiling and bioinformatic analyses of human macrophages stimulated by VE-UHMWPE particles revealed a distinct transcriptional program from macrophages stimulated with UHMWPE particles. Out of the up-regulated genes, IL-27 was found to be significantly elevated in macrophages cultured with VE-UHMWPE particles as compared to these with UHMWPE particles (p = 0.0084). Furthermore, we studied the potential anti-osteolytic function of IL-27 in osteolysis murine model. Interestingly, administration of recombinant IL-27 onto calvariae significantly alleviated osteolytic lesions triggered by UHMWPE particles (p = 0.0002). Likewise, IL-27 inhibited differentiation of osteoclasts (p = 0.0116) and reduced inflammatory response (p < 0.0001) elicited by conventional UHMWPE particles in vitro. This is the first study demonstrating the involvement of IL-27 in macrophage response to VE-UHMWPE particles and its regulatory role in osteolysis. Our data highlight a novel therapeutic agent for treatment of inflammatory osteolysis induced by polyethylene debris. STATEMENT OF SIGNIFICANCE: Aseptic loosening due to inflammatory osteolysis remains the major cause of arthroplasty failure and represents a substantial economic burden worldwide. Ideal approach to prevent this failure should be directed to minimize inflammatory response triggered by wear particles at the site of implant. Understanding the mechanism by which VE-UHMWPE particles triggers lesser cellular responses and reduced osteolysis as compared to conventional UHMWPE particles may aid in discovery of regulatory factors. In the current study, we reported that IL-27 is a potent regulator of inflammatory osteolysis involved in the reduced biologic activities and osteolytic potentials associated with VE-UHMWPE particles. Initiating the production IL-27 in vivo after total joint arthroplasties might be a novel strategy to prolong the life-spam of implant., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Periprosthetic osteolysis is a major cause of implant failure in total hip replacements. Aseptic loosening caused by osteolytic lesions is associated with the production of bioactive wear particles from the articulations of implants. Wear particles infiltrate the surrounding tissue of implants, promoting inflammation as well as bone resorption. Osteocytes have been shown to both regulate physiological osteoclastogenesis and directly remodel their perilacunar bone matrix by the process of osteocytic osteolysis. We hypothesise that osteocytes respond to wear debris of orthopaedic implant materials by adopting a pro-catabolic phenotype and thus contribute to periprosthetic osteolysis through the known pathways of bone loss. Osteocyte responses to particles derived from clinically relevant materials, ultra-high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (XLPE) and metal alloys, Ti6Al4V and CoCrMo, were examined in vitro in human primary osteocyte-like cultures. Osteocyte-like cells exposed to both polyethylene and metal wear particle types showed upregulated expression of catabolic markers associated with osteocytic osteolysis, MMP13, carbonic anhydrase 2 (CA2) and cathepsin K (CTSK). In addition, pro-osteoclastogenesis markers RANKL and M-CSF were induced, as well as the expression of pro-inflammatory cytokines, IL-6 and TNFα, albeit with different kinetics. These findings suggest a previously unrecognised action of wear particles of multiple orthopaedic materials on osteocytes, and suggest a multifaceted role for osteocytes in periprosthetic osteolysis. STATEMENT OF SIGNIFICANCE: This study addresses periprosthetic osteolysis, a major clinical problem leading to aseptic loosening of orthopaedic implants. It is well accepted that wear particles of polyethylene and of other implant materials stimulate the activity of bone resorbing osteoclasts. Our recent work provided evidence that commercial particles of ultra-high molecular weight polyethylene (UHMWPE) stimulated osteocytes to adopt a bone catabolic state. In this study we demonstrate for the first time that particles derived from materials in clinical use, conventional UHMWPE, highly cross-linked polyethylene (XLPE), and Ti6Al4V and CoCrMo metal alloys, all stimulate human osteocyte activities of osteocyte-regulated osteoclastogenesis, osteocytic osteolysis, proinflammatory responses, osteocyte apoptosis, albeit to varying extents. This study provides further mechanistic insight into orthopaedic wear particle mediated bone disease in terms of the osteocyte, the most abundant and key controlling cell type in bone., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Surface of ultra-high-molecular-weight polyethylene (UHMWPE) was modified by chemical methods. Surface was firstly activated by Piranha solution and then grafted with selected amino-compounds (cysteamine, ethylenediamine or chitosan). The next step was grafting of some borane cluster compounds, highly fluorescent borane hydride cluster anti-B 18 H 22 or its thiolated derivative 4,4'-(HS) 2 -anti-B 18 H 20 . Polymer foils were studied using various methods to characterize surface chemistry (X-ray photoelectron spectroscopy), roughness and morphology (atomic force microscopy, scanning electron microscopy), chemistry and polarity (electrokinetic analysis), wettability (goniometry) and photophysical properties (UV-Vis spectroscopy) before and after modification steps. Subsequently some kinds of antimicrobial tests were performed. Immobilization of anti-B 18 H 22 in small quantities onto UHMWPE surface leads to materials with a luminescence. Samples grafted with borane clusters showed significant inhibition of growth for gram-positive bacteria (S. epidermidis). These approaches can be used for (i) luminophores on the base of polymers nanocomposites development and/or (ii) preparation of materials with antimicrobial effects., (Copyright © 2018 Elsevier B.V. All rights reserved.)

High-density polyethylene (HDPE)-based and ultra-high molecular weight polyethylene (UHMWPE)-based composites with carbonaceous reinforcements are being widely investigated for biomedical applications. The enhancement of material properties critically depends on the nature, amount and compatibility of the reinforcement with the polymeric matrix. To this end, this study demonstrates the efficacy of a 'dual' hybrid approach of incorporating modified inorganic nanofiller into an optimized polyethylene blend. In particular, a unique synthesis strategy was adopted to design a covalently bonded maleated polyethylene (mPE) grafted modified graphene oxide (mGO) hybrid nanocomposite. In this scheme, polyethyleneimine (PEI) was initially attached onto GO to synthesize amine functionalized GO (GO-PEI). This is followed by mPE grafting, resulting in mGO. Melt-extrusion together with injection moulding of a polymer mix (60% HDPE-40% UHMWPE) with different proportions (less than or equal to 3 wt%) of surface functionalized GO was conducted to develop nanocomposites of different sizes and shapes. When compared with unreinforced PE blend, the nanocomposites with 1 wt% mGO exhibited an increase in ultimate tensile strength by 120% (up to 65 MPa) and elastic modulus by 40% (up to 908 MPa). The uniform dispersion of modified GO nanofillers, confirmed using X-ray micro-computed tomography and transmission electron microscopy, facilitated effective interfacial adhesion and compatibility with the hybrid polymer matrix. The variation in mechanical properties with GO/mGO addition to PE blend was critically discussed in reference to the structural modification of GO, crystallinity and nature of dispersion of fillers. Importantly, the nanocomposites support the attachment and proliferation of C2C12 murine myoblast cells over 3 days in culture in a statistically insignificant manner with respect to polymer blends without any nanofiller. Taken together, the experimental results suggest that HDPE/UHMWPE/mGO is a promising biomaterial for bone tissue engineering applications.

Polyelectrolyte multilayers (PEMs) assembled layer-by-layer have emerged as functional polymer films that are both stable and capable of containing drug molecules for controlled release applications. Most of these applications concentrate on sustained release, where the concentration of the released molecules remains rather constant with time. However, high-efficiency delivery requires obtaining high local concentrations at the vicinity of the cells, which is achieved by triggered release. Here, we show that a nanopatterned PEM platform demonstrates superior properties with respect to drug retention and triggered delivery. A chemically modified block copolymer film was used as a template for the selective deposition of poly(ethylene imine) and a charged derivative of the electroactive poly(3,4-ethylenedioxythiophene) together with a drug molecule. This nanopatterned PEM shows the following advantages: (1) high drug loading; (2) enhanced retention of the bioactive molecule; (3) release triggered by an electrochemical stimulus; (4) high efficacy of drug delivery to cells adsorbed on the surface compared to the delivery efficacy of a similar concentration of drug to cells suspended in a solution.

Surface topography has a profound effect on the development of the nervous system, such as neuronal differentiation and morphogenesis. While the interaction of neurons and the surface topography of their local environment is well characterized, the neuron-topography interaction during the regeneration process remains largely unknown. To address this question, an anisotropic surface topography resembling linear grooves made from poly(ethylene-vinyl acetate) (EVA), a soft and biocompatible polymer, using nanoimprinting, is established. It is found that neurons from both the central and peripheral nervous system can survive and grow on this grooved surface. Additionally, it is observed that axons but not dendrites specifically align with these grooves. Furthermore, it is demonstrated that neurons on the grooved surface are capable of regeneration after an on-site injury. More importantly, these injured neurons have an accelerated and enhanced regeneration. Together, the data demonstrate that this anisotropic topography guides axon growth and improves axon regeneration. This opens up the possibility to study the effect of surface topography on regenerating axons and has the potential to be developed into a medical device for treating peripheral nerve injuries., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

UHMWPE granule could induce macrophages and inflammatory responses in interfacial tissues, which eliminated the wear debris of UHMWPE component and further induced dissolution of the surrounding bone, leading aseptic loosening. However, the mechanism of synovial cells, especially fibroblast-like synovial (FLS) cells response to UHMWPE, remains unknown. Herein we choose FLS cells as research object. Vimentin (+) CD68 (-) was identified by flow cytometry and immunofluorescent staining assay, and the cells were identified as FLS cells, which was consistent with the experimental requirements. The inhibitory evaluation showed that UHMWPE could significantly promote the proliferation and inhibit apoptosis of FLS cells in dose- and time-dependent manners and increase the levels of proinflammatory cytokines, including IL-6, IL-1 β , TNF- α , PGE2, MMP2, and LOX. UHMWPE also can induce the expression of mIL-6R protein in FLS cells and further investigate the relationship between apoptosis and inflammation. Interestingly enough, when we added the interleukin-6 receptor antagonist (IL-6RA), the expression levels of proapoptosis-related proteins increased; in other words, UHMWPE-induced antiapoptosis diminished by IL-6RA (50 μ g/ml). Taken together, these findings clearly demonstrated that UHMWPE promote growth in FLS cells through upregulating inflammatory factors to produce antiapoptotic effect.

Poly(ethylene imine)s (PEIs) have been widely studied for biomedical applications, including antimicrobial agents against potential human pathogens. The interactions of branched PEIs (B-PEIs) with environmentally relevant microorganisms whose uncontrolled growth in natural or engineered environments causes health, economic, and technical issues in many sectors of water management are studied. B-PEIs are shown to be potent antimicrobials effective in controlling the growth of environmentally relevant algae and cyanobacteria with dual-functionality and selectivity. Not only did they effectively inhibit growth of both algae and cyanobacteria, mostly without causing cell death (static activity), but they also selectively flocculated cyanobacteria over algae. Thus, unmodified B-PEIs provide a cost-effective and chemically facile framework for the further development of effective and selective antimicrobial agents useful for control of growth and separation of algae and cyanobacteria in natural or engineered environments., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hybrid nanoparticles of poly(methylmethacrylate) synthesized in the presence of poly (diallyldimethyl ammonium) chloride by emulsion polymerization exhibited good colloidal stability, physical properties, and antimicrobial activity but their synthesis yielded poor conversion. Here we create antimicrobial coatings from casting and drying of the nanoparticles dispersions onto model surfaces such as those of silicon wafers, glass coverslips, or polystyrene sheets and optimize conversion using additional stabilizers such as cetyltrimethyl ammonium bromide, dioctadecyldimethyl ammonium bromide, or soybean lecithin during nanoparticles synthesis. Methodology included dynamic light scattering, determination of wettability, ellipsometry of spin-coated films, scanning electron microscopy, and determination of colony forming unities (log CFU/mL) of bacteria after 1 h interaction with the coatings. The additional lipids and surfactants indeed improved nanoparticle synthesis, substantially increasing the conversion rates by stabilizing the monomer droplets in dispersion during the polymerization. The coatings obtained by spin-coating or casting of the nanoparticles dispersions onto silicon wafers were hydrophilic with contact angles increasing with the amount of the cationic polymer in the nanoparticles. Against Escherichia coli and Staphylococcus aureus , bacteria cell counts were reduced by approximately 7 logs upon interaction with the coatings, revealing their potential for several biotechnological and biomedical applications.

Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NO to wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describe the development of supramolecular interpolymer complex hydrogels comprising PEO-PPO-PEO (F127) micelles embedded in a poly(acrylic acid) (PAA) matrix, with S-nitrosoglutathione (GSNO) molecules dissolved in the hydrophilic domain. We show that PAA:F127/GSNO hydrogels start releasing NO upon hydration at rates controlled by their rates of water absorption. SAXS measurements indicate that the supramolecular structure of the hydrogels retains long-range order domains of F127 micelles. The PAA/F1227 hydrogels displayed dense morphologies and reduced rates of hydration. The NO release rates remain constant over the first 200 min, are directly correlated with the hydration rates of the PAA:F127/GSNO hydrogels, and can be modulated in the range of 40 nmol/g h to 1.5 μmol/g h by changing the PAA:F127 mass ratio. Long-term NO-release profiles over 5 days are governed by the first-order exponential decay of GSNO, with half-lives in the range of 0.5-3.4 days. A preliminary in vivo study on full-thickness excisional wounds in mice showed that topical NO release from the PAA:F127/GSNO hydrogels is triggered by exudate absorption and leads to increased angiogenesis and collagen fiber organization, as well as TGF-β, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue. In summary, these results suggest that hydration-controlled NO release from topical PAA:F127/GSNO hydrogels is a potential strategy for enhancing wound healing., Statement of Significance: The topical delivery of nitric oxide (NO) to wounds may provide significant beneficial results and represent a promising strategy to treat chronic wounds. However, wound dressings capable of releasing NO after application and allowing the modulation of NO release rates, demand new platforms. Here, we describe a novel strategy to overcome these challenges, based on the use of supramolecular poly(acrylic acid) (PAA):F127 hydrogels charged with the NO donor S-nitrosoglutathione (GSNO) from whereby the NO release can be triggered by exudate absorption and delivered to the wound at rates controlled by the PAA:F127 mass ratio. Preliminary in vivo results offer a proof of concept for this strategy by demonstrating increased angiogenesis; collagen fibers organization; and TGF-β, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue after topical treatment with a PAA:F127/GSNO hydrogel., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Telechelic antimicrobial poly(2-oxazoline)s with quaternary ammonium (quat) end groups are shown to be potent antimicrobial polymers against Gram-positive bacterial strains. In this study, the activity against the Gram-negative bacterium Escherichia coli is additionally implemented by hydrolyzing the poly(2-methyl-2-oxazoline) with two quart end groups to poly(ethylene imine) (PEI). The resulting telechelic polycations are active against Staphylococcus aureus and E. coli. The contribution of the PEI backbone is determined by measuring the antimicrobial activity in the presence of calcium ions. The influence of PEI on the overall activity strongly depends on the molecular weight and increases with higher mass. The PEI dominates the activity against E. coli at lower masses than against S. aureus. The quart end groups require an alkyl substituent of dodecyl or longer to dominate the antimicrobial activity. Additionally, PEI and quart end groups act synergistically., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, we performed a virtual mobile-bearing unicompartmental knee arthroplasty (UKA) on the contact pressure in the tibial insert and articular cartilage by using finite element (FE) analysis to understand clinical observations and elaborate on the potential risks associated with a joint line preservation such as wear on tibial insert and osteoarthritis on other compartment. Neutral position of the knee joint was defined in 0 mm joint line, and contact pressure between tibial insert and articular cartilage varies with respect to changes of joint line. Therefore, evaluation of contact pressure may provide the degree of joint line preservation. The FE model for the joint line was developed using a perpendicular projection line from the medial tibial plateau to the anatomical axis. Seven FE models for joint lines in cases corresponding to ± 6, ± 4, ± 2, and 0 mm were modeled and analyzed in normal level walking conditions. The maximum contact pressure on the superior and inferior surfaces of the polyethylene insert increased when the joint line became positive while the maximum contact pressure on the articular cartilage increased when the joint line became negative. The increase in the maximum contact pressure in the positive joint line exceeded that in the negative joint line, and this lead to an unsymmetrical maximum contact pressure distribution with respect to the joint line from a 0 reference. The joint line elevation was sensitive to increases or decreases in maximum contact pressures in the mobile-bearing UKA. The findings of the study determined that postoperative joint line preservation is important in mobile-type bearing UKA.

Osteolysis associated with an implanted prosthesis is the major cause of failure in prosthesis implantation, and a severe public health issue worldwide. The type of bone metabolism associated with this disorder has been a major focus for improving the outcomes of patients with osteolysis. The role of metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1; a member of the long coding RNA family) during the onset of osteolysis and the related molecular regulatory mechanism in ultra‑high molecular weight polyethylene (UHMWPE)‑treated hFOB 1.19 cells were investigated in the current study. The effect of MALAT1 knockdown on cell viability, cell apoptosis and osteolysis‑associated signaling were also examined, and the interactions that occurred between MALAT1 and an anti‑osteolysis molecule, microRNA (miR)‑22‑5p were investigated. Additionally, knockdown of vascular endothelial growth factor (VEGF) exerted similar biological effects as observed following miR‑22‑5p overexpression. The data showed that MALAT1 and pro‑osteolysis indicators, receptor activator of nuclear factor‑κB ligand (RANKL) and VEGF were upregulated in clinical interface membrane samples. Knockdown of MALAT1 inhibited the growth of UHMWPE‑treated hFOB 1.19 cells, and this effect was associated with the upregulation of OPG, and downregulation of RANKL and VEGF. Results of a dual luciferase assay confirmed the interaction between VEGF and miR‑22‑5p, and also between MALAT1 and miR‑22‑5p. Additionally, subsequent assays indicated that overexpression of MALAT1 suppressed the anti‑osteolysis effect of miR‑22‑5p, which would further induce VEGF expression. The data indicated that MALAT1 has an in port ant role in the onset of osteolysis via its ability to induce RANKL expression and inhibit the effect of miR‑22‑5p.

Polymeric sublaminar cables have a number of advantages over metal cables in the field of spinal deformity surgery, with decreased risk of neurological injury and potential for higher correction forces as the two most predominant. However, currently available polymer cables are radiolucent, precluding postoperative radiological assessment of instrumentation stability and integrity. This study provides a preclinical assessment of a woven UHMWPE cable made with radiopaque UHMWPE fibers. Our primary goal was to determine if the addition of a radiopacifier negatively affects the mechanical properties of UHMWPE woven cables. Tensile mechanical properties were determined and compared to suitable controls. Radiopacity was evaluated and radiopacifier leaching was assessed in vitro and in vivo. Finally, in vivo bismuth organ content was quantified after a 24-week implantation period in sheep. Results show that the mechanical properties of woven UHMWPE cables were not deleteriously affected by the addition of homogenously dispersed bismuth oxide particles within each fiber. Limited amounts of bismuth oxide were released in vitro, well below the toxicological threshold. Tissue concentrations lower than generally accepted therapeutic dosages for use against gastrointestinal disorders, well below toxic levels, were discovered in vivo. These results substantiate controlled clinical introduction of these radiopaque UHMWPE cables. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 771-779, 2018., (© 2017 Wiley Periodicals, Inc.)

In the field of total joint replacements, polymer nanocomposites are being investigated as alternatives to ultrahigh molecular weight polyethylene (UHMWPE) for acetabular cup bearings. The objective of this study was to investigate the wear performance and biocompatibility of UHMWPE/graphene oxide (GO) nanocomposites. This study revealed that low concentrations of GO nanoparticles (0.5 wt %) do not significantly alter the wear performance of UHMWPE. In contrast, the addition of higher concentrations (2 wt %) led to a significant reduction in wear. In terms of biocompatibility, UHMWPE/GO wear particles did not show any adverse effects on L929 fibroblast and PBMNC viability at any of the concentrations tested over time. Moreover, the addition of GO to a UHMWPE matrix did not significantly affect the inflammatory response to wear particles. Further work is required to optimize the manufacturing processes to improve the mechanical properties of the nanocomposites and additional biocompatibility testing should be performed to understand the potential clinical application of these materials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 183-190, 2018., (© 2016 Wiley Periodicals, Inc.)

The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

Ultra-high-molecular-weight polyethylene (UHMWPE) has been applied in orthopedics, as the materials of joint prosthesis, artificial ligaments, and sutures due to its advantages such as high tensile strength, good wear resistance, and chemical stability. However, postoperative osteolysis induced by UHMWPE wear particles and poor bone-implant healing interface due to scarcity of osseointegration is a significant problem and should be solved imperatively. In order to enhance its affinity to bone tissue, vascular endothelial growth factor (VEGF) was loaded on the surface of materials, the loading was performed by silk fibroin (SF) coating to achieve a controlled-release delivery. Several techniques including field emission scanning electron microscopy (FESEM) and attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) and water contact angle measurement were used to validate the effectiveness of introduction of SF/VEGF. The result of ELISA demonstrated that the release of VEGF was well maintained up to 4 weeks. The modified UHMWPE was evaluated by both in vitro and in vivo experiments. According to the results of FESEM and cell counting kit-8 (CCK-8) assay, bone marrow mesenchymal stem cells cultured on the UHMWPE coated with SF/VEGF and SF exhibited a better proliferation performance than that of the pristine UHMWPE. The model rabbit of anterior cruciate ligament reconstruction was used to observe the graft-bone healing process in vivo. The results of histological evaluation, microcomputed tomography (micro-CT) analysis, and biomechanical tests performed at 6 and 12 weeks after surgery demonstrated that graft-bone healing could be significantly improved due to the effect of VEGF on angiogenesis, which was loaded on the surface by SF coating. This study showed that the method loading VEGF on UHMWPE by SF coating played an effective role on the biological performance of UHMWPE and displayed a great potential application for anterior cruciate ligament reconstruction., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Particle-induced osteolysis and periprosthetic joint infection (PJI) are closely associated with periprosthetic tissue immune function. The objective of this study was to determine the effects of polyethylene particles on inflammation and response against S. aureus. Effects that vitamin E-diffused cross-linked UHMWPE (VE-PE) particles had on apoptosis, inflammation, and bactericidal activities compared to virgin cross-linked UHMWPE (control PE) particles were examined. Murine RAW 264.7 macrophages exposed to VE-PE particles in vitro were less apoptotic, secreted less tumor necrosis factor (TNF)-α, and responded more effectively against lipopolysaccharide or S. aureus compared to control PE particles. Implantation of VE-PE particles in murine calvaria in vivo caused less reactive oxygen species generation, less apoptosis, and less osteolysis compared to control PE particles. Implantation of PE particles in mice calvaria for 28 days, followed by inoculation with S. aureus in the same site where PE particles were implanted, demonstrated enhanced S. aureus clearance in the VE-PE group at day 33 after inoculation. These findings indicate that VE-PE particles might be less inflammatory and might preserve innate immunity of local tissue, allowing for enhanced clearance of bacteria., (Copyright © 2017. Published by Elsevier Ltd.)

In recent years, much effort has been focused on an appropriate combination of chemotherapeutic drugs and nucleic acids to exploit additive or synergistic therapeutic effects and overcome many obstacles such as the reduction of side effects and drug resistance. Short hairpin RNA (shRNA) has designed to allow the production of small interfering RNA (siRNA) within the cells and offer long-lasting silencing of target genes. In this study, alkyl-modified polyethylenimine (PEI 10 kD) was used for co-delivery of doxorubicin (DOX) encapsulated into poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and Bcl-xL shRNA (one class of molecules that block apoptosis of tumor cells) into breast cancer cells. Our results demonstrated that modification of PEI with alkyl chain could enhance the induction of apoptosis in tumor cells by suppression of Bcl-xL gene using Bcl-xL shRNA more than PEI alone. On the other hand, DOX encapsulated into PLGA had more synergistic effect with shRNA in comparison with DOX alone. In conclusion, combination of PLGA-DOX NPs and alkyl-PEI/shRNA complexes may have promising applications in breast cancer therapy.