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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.

Purpose Polymeric mesh implantation has become the golden standard in hernia repair, which nowadays is one of the most frequently performed surgeries in the world. However, many biocompatibility issues remain to be a concern for hernioplasty, with chronic pain being the most notable post-operative complication. Oxidative stress appears to be a major factor in the development of those complications. Lack of material inertness in vivo and oxidative environment formed by inflammatory cells result in both mesh deterioration and slowed healing process. In a pilot in vivo study, we prepared and characterized polypropylene hernia meshes with vitamin E (α-tocopherol)-a potent antioxidant. The results of that study supported the use of vitamin E as potential coating to alleviate post-surgical inflammation, but the pilot nature of the study yielded limited statistical data. The purpose of this study was to verify the observed trend of the pilot study statistically. Methods In this work, we conducted a 5-animal experiment where we have implanted vitamin E-coated and uncoated control meshes into the abdominal walls of rabbits. Histology of the mesh-adjacent tissues and electron microscopy of the explanted mesh surface were conducted to characterize host tissue response to the implanted meshes. Results As expected, modified meshes exhibited reduced foreign body reaction, as evidenced by histological scores for fatty infiltrates, macrophages, neovascularization, and collagen organization, as well as by the surface deterioration of the meshes. Conclusion In conclusion, results indicate that vitamin E coating reduces inflammatory response following hernioplasty and protects mesh material from oxidative deterioration.

The majority of periprosthetic joint infections occur shortly after primary joint replacement (

Total joint replacement is a widely used and successful surgical approach. Approximately 7 million US adults are currently living with a hip or knee replacement. However, the surgical procedures for total joint replacement are associated with significant postoperative pain, and current strategies do not adequately address this pain, which leads to patient dissatisfaction, reduced mobility, and increased risk of opioid addiction. We hypothesized that the ultra-high-molecular-weight polyethylene (UHMWPE) bearing surfaces used in total joint prosthetics could provide sustained release of the local anesthetic bupivacaine to provide relief from joint pain for an extended period of time after surgery. In this paper, we describe the production of bupivacaine-loaded UHMWPE (BPE) and measure the in vitro bupivacaine release kinetics of BPE. We found that bupivacaine could be released from BPE at clinically relevant rates for up to several days and that BPE possesses antibacterial effects. Therefore, bupivacaine-loaded UHMWPE is a promising material for joint replacement prostheses, and future studies will evaluate its safety and efficacy in in vivo models. STATEMENT OF SIGNIFICANCE: Total joint replacement is associated with significant pain and risk of infection. In our paper, we introduce bupivacaine-loaded ultra-high-molecular-weight polyethylene (BPE), which releases bupivacaine, a pain-treating drug, at doses comparable to currently used doses. Additionally, BPE inhibits the growth of infection-causing bacteria. Therefore, BPE may be able to reduce both postsurgical pain and risk of infection, potentially treating two of the most prominent complications associated with total joint replacement. To our knowledge, this is the first development of a material that can address both complications, and devices incorporating BPE would represent a significant advancement in joint arthroplasty prosthetics. More generally, the incorporation of therapeutic agents into ultra-high-molecular-weight polyethylene could impact many orthopedic procedures owing to its ubiquity.

Aims We propose a state-of-the-art temporary spacer, consisting of a cobalt-chrome (CoCr) femoral component and a gentamicin-eluting ultra-high molecular weight polyethylene (UHMWPE) tibial insert, which can provide therapeutic delivery of gentamicin, while retaining excellent mechanical properties. The proposed implant is designed to replace conventional spacers made from bone cement. Methods Gentamicin-loaded UHMWPE was prepared using phase-separated compression moulding, and its drug elution kinetics, antibacterial, mechanical, and wear properties were compared with those of conventional gentamicin-loaded bone cement. Results Gentamicin-loaded UHMWPE tibial components not only eradicated planktonic Staphylococcus aureus, but also prevented colonization of both femoral and tibial components. The proposed spacer possesses far superior mechanical and wear properties when compared with conventional bone cement spacers. Conclusion The proposed gentamicin-eluting UHMWPE spacer can provide antibacterial efficacy comparable with currently used bone cement spacers, while overcoming their drawbacks. The novel spacer proposed here has the potential to drastically reduce complications associated with currently used bone cement spacers and substantially improve patients’ quality of life during the treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):151–157.

Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV2, which is the causative virus for COVID-19, and for other organisms of concern in the hospital environment such as Staphylococcus aureus or Clostridium difficile.The efficacy of inactivation or eradication against various pathogens should be evaluated thoroughly to understand the level of afforded disinfection. Methods commonly used in the sterilization of medical devices such as ionizing radiation, vaporized hydrogen peroxide, and ethylene oxide can provide a high level of disinfection, defined as a 6 log10 reduction, against bacterial spores, considered the most resistant microorganisms. CDC guidance on the decontamination and reuse of N95s also includes the use of moist heat (60°C, 80% relative humidity, 15-30 min) as a possible recommendation based on literature showing preservation of fit efficiency and inactivation of H1N1 on spiked masks.Here, we explored the efficacy of using moist heat under these conditions as a decontamination method for an N95 respirator (3M 1860S, St. Paul, MN) against various pathogens with different resistance; enveloped RNA viruses, Gram (+/-) bacteria, and non-enveloped viruses.

Surface modification with polymer grafting is a versatile tool for tuning the surface properties of a wide variety of materials. From a practical point of view, such a process should be readily scalable and transferable between different substrates and consist of as least number of steps as possible. To this end, a cross-linkable amphiphilic copolymer system that is able to bind covalently to surfaces and form permanently attached networks via a one-step procedure is reported here. This system consists of brushlike copolymers (molecular brushes) made of glycidyl methacrylate, poly(oligo(ethylene glycol) methyl ether methacrylate), and lauryl methacrylate, which provide the final product with tunable reactivity and balance between hydrophilicity and hydrophobicity. The detailed study of the copolymer synthesis and properties has been carried out to establish the most efficient pathway to design and tailor this amphiphilic molecular brush system for specific applications. As an example of the applications, we showed the ability to control the deposition of graphene oxide (GO) sheets on both hydrophilic and hydrophobic surfaces using GO modified with the molecular brushes. Also, the capability to tune the osteoblast cell adhesion with the copolymer-based coatings was demonstrated.

Despite the relative safety of the procedure, hernia repairs are often associated with chronic post-operative pain. Although this complication has been linked among others to mesh deterioration, details of the processes that lead this deterioration are still unknown. This work aims to bridge this gap by analyzing the chemical, physical and structural alterations in hernia repair meshes exposed to oxidative stress in vitro. Here, we developed a methodology to characterize effect of oxidation stress on structure and properties of polymeric hernia repair meshes. It was shown that structural changes in polypropylene meshes exposed to oxidative stress may involve formation of cross-links between the polymer chains, chain scissions, and hydrogen bonds between the carboxyl groups, which are formed in the material during the oxidation. These effects result in mesh stiffening, ultimately leading to chronic post-operative pain. Moreover, we demonstrated that Composix meshes are more vulnerable to the oxidative stress when compared with UltraPro meshes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2225-2234, 2018.

The current prevalence of postoperative chronic pain from hernioplasty procedures employing polymer mesh is close to 30%. Most of the researchers agree that oxidative stress, resulting from the release of oxidants and enzymes during acute inflammatory response, is a key factor in the development of posthernioplasty complications. This results in both the decrease of the biomechanical properties and stiffening of the polymer fibers of the mesh, leading to chronic pain. Moreover, enhanced activity of inflammatory cells can lead to an excessive deposition of connective tissue around the implant. In this study polypropylene hernia repair meshes coated with vitamin E (α-tocopherol), a known antioxidant, were prepared and characterized. The absorption isotherm of vitamin E on the mesh was characterized and a release profile study yielded a promising results, showing sustained release of the drug over a 10-day period. An animal study was conducted, and histological analysis five weeks after implantation exhibited a reduced host tissue response for a modified mesh as compared to a plain mesh, as evidenced by a higher mature collagen to immature collagen ratio, as well as lower level of fatty infiltrates, neovascularization and fibrosis in the case of modified mesh. These results support the use of α-tocopherol as a potential coating in attempt to reduce the extent of postoperative inflammation, and thereby improve long-term outcomes of hernioplasty. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 589-597, 2018.

Cerium oxide nanoparticles (nanoceria) have recyclable antioxidative activity. It has numerous potential applications in biomedical engineering, such as mitigating damage from burns, radiation, and bacterial infection. This mitigating activity is analogous to that property of metabolic enzymes such as superoxide dismutase (SOD) and catalase - scavengers of reactive oxygen species (ROS). Therefore, nanoceria can protect cells from environmental oxidative stress. This therapeutic effect prompted studies of nanoceria and metabolic enzymes as a combination therapy. The activity and structure of SOD, catalase, and lysozyme were examined in the presence of nanoceria. A complementary relationship between SOD and nanoceria motivated the present work, in which we explored a method for simultaneous delivery of SOD and nanoceria. The biocompatibility and tunable degradation of poly(lactic-co-glycolic acid) (PLGA) made it a candidate material for encapsulating both nanoceria and SOD. Cellular uptake studies were conducted along with a cytotoxicity assay. The antioxidative properties of PLGA-nanoceria-SOD particles were verified by adding H2O2 to cell culture and imaging with fluorescent markers of oxidative stress. Our results suggest that PLGA is a suitable encapsulating carrier for simultaneous delivering nanoceria and SOD together, and that this combination effectively reduces oxidative stress in vitro.

Peri-articular delivery of pain medication in joint arthroplasty has the potential to address post-operative pain and decrease the use of systemic opioids. Additionally, the sustained release from a delivery vehicle may be especially impactful in the initial post-operative period when pain is most severe. We recently described a novel approach for the sustained intra-articular delivery of an analgesic (bupivacaine) from an ultra-high molecular weight polyethylene (UHMWPE) bearing surface. A secondary but very significant effect of incorporating bupivacaine in UHMWPE was its antibacterial effect against Staphylococcal species, which are associated with the majority of periprosthetic joint infections. Here, we report on the structure, properties, elution characteristics and antibacterial properties of UHMWPE loaded with the non-steroidal anti-inflammatory drug (NSAID) — tolfenamic acid. We showed that 6 wt% drug loading was optimal for eluting clinically relevant intra-articular and systemic concentrations, for maintaining mechanical properties at a clinically relevant level, and for providing anti-colonization potential against low risk (planktonic) and high risk (biofilm forming) Staphylococcal species. We determined the osteoblast response to the tolfenamic acid-loaded UHMWPE to evaluate the cytotoxicity profile of this novel material. Tolfenamic acid-loaded UHMWPE has the potential to be used as a part of multimodal pain management therapy following arthroplasty and may provide prophylaxis for periprosthetic infection.

The local use of analgesics and antibiotics is common during the treatment of periprosthetic joint infection (PJI). The effect of nonantimicrobial drugs on antibacterial activity is underappreciated in clinical practice. This study focuses on the novel assessment of the combined antibacterial effects of commonly used analgesics and antibiotics against methicillin-sensitive Staphylococcus aureus (MSSA)-pathogen associated with most PJIs. We identified that bupivacaine/lidocaine and ketorolac/gentamicin combinations yielded fractional inhibitory concentration indices below 0.4, indicative of synergistic antibacterial effect. Time-kill curves were used for in-depth characterization of the synergy, and the obtained results demonstrated pronounced synergistic effects of bupivacaine/lidocaine and ketorolac/gentamicin combinations against MSSA.

Despite being a relatively safe surgery, total joint replacement is often associated with two major complications-severe post-operative pain and periprosthetic joint infection. Local sustained delivery of therapeutics to the surgical site has a potential to address these complications more effectively than current clinical approaches. Given that several analgesics were shown to possess antibacterial activity, we propose here to use analgesic-loaded ultra-high molecular weight polyethylene (UHMWPE) as a delivery vehicle to provide antimicrobial effect after an arthroplasty. Three commonly used anesthetics, lidocaine, bupivacaine, and ropivacaine, were analyzed in order to reveal the drug with the highest antibacterial activity against methicillin-sensitive Staphylococcus aureus. Having shown highest antibacterial activity in the bacterial susceptibility tests, bupivacaine was chosen to be incorporated into UHMWPE to provide antibacterial properties. Bupivacaine-loaded UHMWPE possessed moderate dose-dependent antimicrobial properties, decreasing the S. aureus proliferation rate by up to 70%. Biofilm formation was also substanitally inhibited during the first 9 h of culture as quantified by bacterial counts and SEM. This proof-of-concept study is first of its kind to demonstrate that analgesic-loaded UHMWPE can be used as part of a multimodal antimicrobial therapy. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Novel approaches to the prevention of microbial infections after the insertion of orthopedic external fixators are in great demand because of the extremely high incidence rates of such infections, which can reach up to 100% with longer implant residence times. Monolaurin is an antimicrobial agent with a known safety record that is broadly used in the food and cosmetic industries; however, its use in antimicrobial coatings of medical devices has not been studied in much detail. Here, we report the use of monolaurin as an antibacterial coating on external fixators for the first time. Monolaurin-coated Kirschner wires (K-wires) showed excellent antibacterial properties against three different bacterial strains, i.e., methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Staphylococcus epidermidis . Approximately 6.0-log reductions of both planktonic and adherent bacteria were achieved using monolaurin-coated K-wires, but monolaurin-coated K-wires did not show any observable cytotoxicity with mouse osteoblast cell cultures. Overall, monolaurin-coated K-wires could be promising as potent antimicrobial materials for orthopedic surgery.

Despite the relative safety of the procedure, hernia repairs are often associated with chronic post-operative pain. Although this complication has been linked among others to mesh deterioration, details of the processes that lead this deterioration are still unknown. This work aims to bridge this gap by analyzing the chemical, physical and structural alterations in hernia repair meshes exposed to oxidative stress in vitro. Here, we developed a methodology to characterize effect of oxidation stress on structure and properties of polymeric hernia repair meshes. It was shown that structural changes in polypropylene meshes exposed to oxidative stress may involve formation of cross-links between the polymer chains, chain scissions, and hydrogen bonds between the carboxyl groups, which are formed in the material during the oxidation. These effects result in mesh stiffening, ultimately leading to chronic post-operative pain. Moreover, we demonstrated that Composix meshes are more vulnerable to the oxidative stress when compared with UltraPro meshes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2225-2234, 2018.

Polymeric nanoparticles have been extensively studied as drug delivery vehicles both in vitro and in vivo for the last two decades. In vitro methods to assess drug release profiles usually utilize degradation of nanoparticles in aqueous medium, followed by the measurement of the concentration of the released drug. This method, however, is difficult to use for drugs that are poorly water soluble. In this study, a protocol for measuring drug release kinetic using albumin solution as the medium is described. Albumin is a major blood transport protein, which mediates transport of many lipid soluble compounds including fatty acids, hormones, and bilirubin. The use of a dialysis-based system utilizing albumin dialysate solution allows hydrophobic drug release from a diverse set of drug delivery modalities is demonstrated. The method using liposomes and PLGA nanoparticles as drug carriers, and two model hydrophobic drugs, 17β-estradiol, and dexamethasone is validated.

Nanocrystalline cerium-dioxide samples with different coherent-scattering region sizes are analyzed by advanced techniques, specifically, small-angle neutron scattering, X-ray and neutron diffraction, and spectrometry of the chemical shift in the characteristic X-ray lines. The obtained data confirm the presence of the size effect, i.e., the dependence of lattice constants on the size of coherent-scattering regions. Meanwhile, no traces of oxygen nonstoichiometry and a related deviation in the effective degree of cerium oxidation from the standard value are found. The results obtained call into question the Tsunekawa model traditionally used to explain the size effect in this compound.

The novel 2,3,9,10,16,17,23,24-tetra-(15-crown-5)phthalocyaninato indium(III) hydroxide [(15 C 5)4 Pc ] In ( OH )(I) was obtained by direct interaction of tetra-(15-crown-5)-phthalocyanine with indium acetylacetonate with 90% yield. The set of UV-vis, 1 H NMR and MALDI-TOF spectroscopy data allowed the unambiguous interpretation of complex structure. It was shown that the developed synthetic approach can be also used for synthesis of indium(III) 2,3,9,10,16,17,23,24-octabutoxyphthalocyanine [( BuO )8 Pc ] In ( OH )(II). Photophysical characteristics (fluorescence and singlet oxygen quantum yields) of I were established. The photochemical stability of I was compared with tetra-(15-crown-5)-phthalocyanine H 2[(15 C 5)4 Pc ] and aluminum(III) complex [(15 C 5)4 Pc ] Al ( OH ). It was found that cation-induced formation of cofacial dimers [2I × 4MX] ( M = K +, Rb +, X = CO 32-, OPic -, OPiv -, SO 42-, ClO 4-, Br -) resulted in significant enhancement of complex photostability.

Interactions of nanoparticles with biological matter—both somatically and in nature—draw scientists’ attention. Nanoparticulate systems are believed to be our saviors, acting as versatile drug delivery vehicles. However, they can also cause life-threatening bodily damage. One of the most important properties of nanocrystalline cerium dioxide is its antioxidant activity, which decreases the abundance of reactive oxygen species during inflammation. In this paper, we report on synergistic effects of inorganic cerium oxide (IV) nanoparticles conjugated with the antioxidative enzymes superoxide dismutase and catalase on scavenging oxygen and nitrogen radicals.

A new microwave-hydrothermal process has been developed for preparing stable aqueous sols of nanocrystalline ceria. Transmission electron microscopy, UV-Vis spectroscopy, and dynamic light scattering shows that CeO2 nanoparticle size remains unchanged during hydrothermal treatments. Sodium adenosine triphosphate and sodium citrate are proposed for additional stabilization of the sols.

Cerium dioxide and ceria-based materials are widely used as components of polishing mixtures and abrasives, anticorrosive coatings, catalysts, solid-oxide fuel cells, etc. [1, 2]. The interest in cerium dioxide research has considerably increased over the last decade because the transition of this compound to a nanocrystalline state significantly changes its physicochemical properties. In particular, with a decrease in the particle size, the unit cell parameter and the oxygen nonstoichiometry of cerium dioxide increase, its electron and ion conductivities change, and its catalytic and biological activities are enhanced [3‐8]. Current cerium dioxide production methods, including thermal decomposition of cerium(III) and (IV) salts, chemical vapor deposition, microemulsion synthesis, aerosol pyrolysis, etc., usually either fail to give CeO 2 nanoparticles of controlled size, or require expensive reagents and equipment, thus preventing practical application. Therefore, in this work, we propose a new method for synthesizing loosely aggregated well-crystallized CeO 2 nanoparticles of controlled size by hydrothermal microwave treatment of ion-exchanged sols. To obtain the initial hydrated cerium dioxide sols, Amberlite IRA 410 CL ion-exchange resin in the OH form was gradually added to a 0.013 M Ce(NO 3 ) 3 solution until pH 10.0. The resulting stable sols were filtered off from the resin, placed in 40%-filled 100-mL polytetrafluoroethylene autoclaves, and subjected to hydrothermal microwave treatment in a Berghof MWS-3* microwave digestion system at 120 and 180 ° C for 2 h. After the treatment, the autoclaves were cooled in air. The products were centrifuged off, repeatedly washed with distilled water, and dried for 2 h in air at 60 ° C. Reference experiments were carried out under similar conditions, with the initial suspensions being hydrated cerium dioxide precursors precipitated from Ce(NO 3 ) 3 solutions by aqueous ammonia. In some experiments, not only the experimental temperature but also the experiment duration was varied (to 6 h). Cerium dioxide synthesis under ordinary hydrothermal conditions was performed in a Parr 4793 reactor with a polytetrafluoroethylene insert equipped with a Parr 4836 temp controller. X-ray diffraction phase analysis (XRD) of the solidphase synthesis products was performed with a Rigaku D/MAX 2500 rotating-anode diffractometer ( Cu K α radiation). The coherent scattering domain sizes D CSD were calculated by the Selyakov‐Scherrer formula

N-doped nanocrystalline titania microspheres with controlled visible light absorption were obtained by a new route utilizing a heterogeneous hydrolysis of TiCl4 vapor with reactive droplets of aqueous aerosols, followed by instant calcination of the products in a preheated flow reactor. Thus prepared separate microspheres with a diameter of 0.5–3 microns were found to consist of anatase or rutile nanocrystals, depending on the parameters of the synthesis. Doped titania samples with different nitrogen contents were synthesized using water solutions with various concentrations of urea in the hydrolyzing aerosols. N− species were found to be a major form of nitrogen impurity. A plausible mechanism for the incorporation of nitrogen into titanium dioxide was proposed. The photocatalytic activity of the obtained powders under UV-visible or visible illumination was found to have a complex dependence on the calcination temperature and the titania doping level.