F127-SE-tLAP thermosensitive hydrogel alleviates bleomycin-induced skin fibrosis via TGF-ß/Smad pathway.

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. 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-ß1-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.

PDADMAC/Alginate-Coated Gold Nanorod For Eradication of Staphylococcus Aureus Biofilms.

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 (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 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.

Time-Resolved Killing of Individual Bacterial Cells by a Polycationic Antimicrobial Polymer.

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, Mw ≈ 4 × 105 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.

Antibiotic-Loaded Ultrahigh Molecular Weight Polyethylenes.

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.

Vepoloxamer improves functional recovery in rat after traumatic brain injury: A dose-response and therapeutic window study.

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.

Progress in Pluronic F127 Derivatives for Application in Wound Healing and Repair.

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-NH2, 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.

Antibiofilm activity of electrochemically activated water (ECAW) in the control of Salmonella Heidelberg biofilms on industrial surfaces.

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 log10 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.

Facile surface treatment strategy to generate dense lysozyme layer on ultra-high molecular weight polyethylene enabling inhibition of bacterial biofilm formation.

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/cm2 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.

Evaluation of mechanical, antimicrobial, and antioxidant properties of vanillic acid induced chitosan/poly (vinyl alcohol) active films to prolong the shelf life of green chilli.

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.

Insight into the Molecule Impact of Critical-Sized UHMWPE-ALN Wear Particles on Cells by the Alginate-Encapsulated Cell Reactor.

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-1ß 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.

Dual-analgesic loaded UHMWPE exhibits synergistic antibacterial effects against Staphylococci.

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.

Permanent, Antimicrobial Coating to Rapidly Kill and Prevent Transmission of Bacteria, Fungi, Influenza, and SARS-CoV-2.

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 effect of microplastics on the interspecific competition of Daphnia.

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.

Influence of supplement administration of omega-3 on the subcutaneous tissue response of endodontic sealers in Wistar rats.

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.

Determination of optimal concentration of vitamin E in polyethylene liners for producing minimal biological response to prosthetic wear debris.

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.

Air-ozonolysis activation of polyolefins versus use of laden finishing to form contact-active nonwoven materials.

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 O2-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.

Antibacterial and anti-inflammatory ultrahigh molecular weight polyethylene/tea polyphenol blends for artificial joint applications.

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.

The effects of TPL-PEI-CyD on suppressing performance of MCF-7 stem cells.

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-ß1, the MCF-7 cells were assessed by flow cytometry for the proportion of CD44+> CD24- cells; then the CD44>+> CD24- 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-ß1 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.

PEI-modified macrophage cell membrane-coated PLGA nanoparticles encapsulating Dendrobium polysaccharides as a vaccine delivery system for ovalbumin to improve immune responses.

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.

A vitamin E blended highly cross-linked polyethylene acetabular cup results in less wear: 6-year results of a randomized controlled trial in 199 patients.

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.