High-Resolution Additive Manufacturing of a Biodegradable Elastomer with A Low-Cost LCD 3D Printer.

Artificial organs and organs-on-a-chip (OoC) are of great clinical and scientific interest and have recently been made by additive manufacturing, but depend on, and benefit from, biocompatible, biodegradable, and soft materials. Poly(octamethylene maleate (anhydride) citrate (POMaC) meets these criteria and has gained popularity, and as in principle, it can be photocured and is amenable to vat-photopolymerization (VP) 3D printing, but only low-resolution structures have been produced so far. Here, a VP-POMaC ink is introduced and 3D printing of 80 µm positive features and complex 3D structures is demonstrated using low-cost (≈US$300) liquid-crystal display (LCD) printers. The ink includes POMaC, a diluent and porogen additive to reduce viscosity within the range of VP, and a crosslinker to speed up reaction kinetics. The mechanical properties of the cured ink are tuned to match the elastic moduli of different tissues simply by varying the porogen concentration. The biocompatibility is assessed by cell culture which yielded 80% viability and the potential for tissue engineering illustrated with a 3D-printed gyroid seeded with cells. VP-POMaC and low-cost LCD printers make the additive manufacturing of high resolution, elastomeric, and biodegradable constructs widely accessible, paving the way for a myriad of applications in tissue engineering and 3D cell culture as demonstrated here, and possibly in OoC, implants, wearables, and soft robotics.

Dynamic Monte Carlo Simulations of Strain-Induced Crystallization in Multiblock Copolymers: Effects of Asymmetric Block Rigidity.

Thermoplastic elastomers such as polyether-b-polyamides (or -polyesters), polyurethanes (or with -urea) and olefin block copolymers are commonly processed through a stretching process for achieving high elasticity and high toughness in their products, while the size diversity of semicrystalline microdomains of hard blocks appears as the key factor. By means of dynamic Monte Carlo simulations of strain-induced crystallization of locally concentrated and diluted crystallizable blocks alternatingly connected with noncrystallizable blocks in diblock and tetrablock copolymers, we have studied the size diversity of semicrystalline microdomains presumably raised by local concentration fluctuations of crystallizable blocks and found the dilution effects to persist from diblock to tetrablock copolymers. In the present work, we continued to study the effects of asymmetric block rigidity between crystallizable and noncrystallizable blocks on strain-induced crystallization of concentrated and diluted crystallizable blocks in diblock copolymers. The results showed that when crystallizable blocks hold higher thermodynamic rigidity than noncrystallizable blocks, the large semicrystalline domains become larger and the small semicrystalline domains become more, enhancing their size diversity. However, asymmetric kinetic rigidity has little effect. Our observations imply that industrial stretching processing could enhance the toughness of semicrystalline thermoplastic elastomers when their crystallizable blocks hold a higher thermodynamic rigidity relative to noncrystallizable blocks. Our integrated approach paved the way for a better understanding of the structure-property relationship in thermoplastic elastomers.

Polydiketoenamines for a Circular Plastics Economy.

The mismanagement and leakage of plastic waste into the environment are failures of modern society. Once in the environment, plastic waste degrades into microplastics on a time scale dependent on the resin chemistry and the associated biotic or abiotic process. The high surface area of microplastics results in the contamination of ecosystems through the leaching of toxic chemicals compounded with plastics during manufacturing. In addition, the small size of microplastics increases the likelihood that they will be inhaled or ingested, which has led to the bioaccumulation of microplastics with documented harm. Furthermore, microplastics are more readily aerosolized and distributed by weather systems to areas remote from locations where plastic waste has been mismanaged. Consequently, the carbon cycle must now account for plastic waste discharge, degradation, and dispersal in the environment after the end of useful life on a global scale.Circularity in plastics recycling endeavors to solve the waste problem while promoting greater sustainability. Circularity can be conducted at different stages in the plastics life cycle. Post-industrial recycling enabling scrap recovery in manufacturing is desirable for industrial material efficiency. However, the degradation of polymer chains currently limits the extent to which scrap recovery may be practiced repeatedly on the same material, particularly when the conversion of secondary resin to various plastic products is intolerant to deviations in polymer properties. Post-consumer recycling, on the other hand, is desirable for erasing the manufacturing history and use history of plastic-containing products. Post-consumer recycling involves cleaning and sorting plastic waste into bales, followed by mechanical recycling to produce dense feedstocks for downstream chemical processes required for deconstruction, monomer refinement, and secondary resin production. The efficiency and intensity of chemical processes used to recover reusable monomers or polymers remain low for most plastics. Consequently, there is an urgent need for novel polymers with useful or advantageous properties designed for recycling by addressing the challenges of resource recovery for reuse.In this Account, I discuss the design, discovery, and development of circular plastics based on the chemistry of polydiketoenamines. The diketoenamine bond provides a vantage point for the creation of thermoplastics, elastomers, and thermosets from polytopic triketone and amine monomers. The dynamic covalent character of the diketoenamine bond can be exploited during scrap recovery to provide resilience during mechanical recycling, maintaining baseline properties of the primary resin through multiple cycles of reuse. Furthermore, the hydrolyzability of the diketoenamine bond in strong acid can be exploited for efficient monomer recovery during chemical recycling. A systems-level analysis of polydiketoenamine circularity reveals substantive benefits in low-carbon manufacturing as well as a context to quantify the market potential, identifying use cases where circularity might be most effective. Leveraging these insights, it is possible to guide the process chemistry development necessary to scale monomer and resin production to meet imminent needs for more circular plastics in the market. These insights also provide a glimpse into the underlying molecular mechanisms critical to circularity in a new plastics economy while firmly establishing a role for creativity in polymer chemistry to provide innovative solutions.

Digital assessment of properties of the three different generations of dental elastomeric impression materials.

BACKGROUND: This study aimed to compare the dimensional accuracy, hydrophilicity and detail reproduction of the hybrid vinylsiloxnether with polyether and polyvinylsiloxane parent elastomers using modified digital techniques and software. This was done in an attempt to aid in solving the conflict between the different studies published by competitive manufacturers using different common manual approaches. METHODS: A polyether, polyvinylsiloxanes and vinyl polyether silicone hybrid elastomeric impression materials were used in the study. Dimensional accuracy was evaluated through taking impressions of a metallic mold with four posts representing a partially edentulous maxillary arch, that were then poured with stone. Accuracy was calculated from the mean of measurements taken between fixed points on the casts using digital single-lens reflex camera to produce high-resolution digital pictures for all the casts with magnification up to 35×. Hydrophilicity was assessed by contact angle measurements using AutoCAD software. The detail reproduction was measured under dry conditions according to ANSI/ADA Standard No. 19 and under wet conditions as per ISO 4823. A metallic mold was used with three V shaped grooves of 20, 50, and 75 µm width. Specimens were prepared and examination was made immediately after setting using digital images at a magnification of 16×. RESULTS: The hybrid impression (0.035 mm) material showed significantly higher dimensional accuracy compared to the polyether (0.051 mm) but was not as accurate as the polyvinyl siloxane impression material (0.024 mm). The contact angles of the hybrid material before and after setting was significantly lower than the parent materials. With regard to the detail reproduction, the three tested materials were able precisely to reproduce the three grooves of the mold under dry conditions. Whereas, under wet conditions, the hybrid material showed higher prevalence of well-defined reproduction of details same as polyether but higher than polyvinylsiloxane that showed prevalence of details with loss of sharpness and continuity. CONCLUSIONS: The digital technique used could be a more reliable and an easier method for assessment of impression materials properties. The hybridization of polyvinyl siloxane and polyether yielded a promising material that combines the good merits of both materials and overcomes some of their drawbacks.

High-spatial-resolution VOCs emission from the petrochemical industries and its differential regional effect on soil in typical economic zones of China.

Volatile organic compounds (VOCs) are toxic to the ecological environment. The emission of VOCs into the atmosphere has already caused attention. However, few studies focus on their regional effects on soil. As a major VOCs source in China, research on the effect of petrochemical industry on the environment is urgent and essential for regional control and industrial layout. This study established national VOCs emission inventory of five petrochemical sub-industries and spatial distribution based on consumption of raw material or products' yield and 28,888 factories. The VOCs emissions showed continuously increasing trend from 2008 to 2019, with cumulative 1.83 × 107 t, wherein these from rapid economic development zones accounted for 66.10%. The detected concentrations of VOCs in various industries combined with meteorological parameters were used in Resistance Model to quantify regional dry deposition. Higher concentrations of 111 VOC species were 238.27, 260.01, 207.54 µg·m-3 from large-scale enterprises for crude oil and natural gas extraction, oil processing, synthetic rubber and resin, leading to higher deposition ratios of 0.81%-0.94%, 0.70%-0.81%, 1.50%-1.75% in rapid economic development zones, respectively. The regional climate condition played a dominant role. Annual VOCs dry deposition amount in rapid economic development zones was calculated to be totally 6.38 × 103 t using obtained deposition ratios and emissions, with 3.21 × 103 t in Bohai Economic Rim (BER), 2.42 × 103 t in Yangtze River Economic Belt (YREB), 748.43 t in Pearl River Delta (PRD). Generally, crude oil and natural gas extraction, oil processing, synthetic rubber and resin contributed 13.09%, 57.77% and 29.14%, respectively. The proportion of synthetic rubber and resin for dry deposition increased by 5.04%-18.81% compared with VOCs emissions in BER and YREB. In contrast, it declined from 45.52% for emission to 29.86% for deposition due to absolute dominance of small-scale enterprises in PRD. Overall, VOCs control from oil processing was significant, especially in BER.

Precision-porous polyurethane elastomers engineered for application in pro-healing vascular grafts: Synthesis, fabrication and detailed biocompatibility assessment.

Unmet needs for small diameter, non-biologic vascular grafts and the less-than-ideal performance of medium diameter grafts suggest opportunities for major improvements. Biomaterials that are mechanically matched to native blood vessels, reduce the foreign body capsule (FBC) and demonstrate improved integration and healing are expected to improve graft performance. In this study, we developed biostable, crosslinked polyurethane formulations and used them to fabricate scaffolds with precision-engineered 40 µm pores. We matched the scaffold mechanical properties with those of native blood vessels by optimizing the polyurethane compositions. We hypothesized that such scaffolds promote healing and mitigate the FBC. To test our hypothesis, polyurethanes with 40 µm pores, 100 µm pores, and non-porous slabs were implanted subcutaneously in mice for 3 weeks, and then were examined histologically. Our results show that 40 µm porous scaffolds elicit the highest level of angiogenesis, cellularization, and the least severe foreign body capsule (based on a refined assessment method). This study presents the first biomaterial with tuned mechanical properties and a precision engineered porous structure optimized for healing, thus can be ideal for pro-healing vascular grafts and in situ vascular engineering. In addition, these scaffolds may have wide applications in tissue engineering, drug delivery, and implantable device.

Home intravenous antibiotherapy and the proper use of elastomeric pumps: Systematic review of the literature and proposals for improved use.

Over several decades, the economic situation and consideration of patient quality of life have been responsible for increased outpatient treatment. It is in this context that outpatient antimicrobial treatment (OPAT) has rapidly developed. The availability of elastomeric infusion pumps has permitted prolonged or continuous antibiotic administration by dint of a mechanical device necessitating neither gravity nor a source of electricity. In numerous situations, its utilization optimizes administration of time-dependent antibiotics while freeing the patient from the constraints associated with infusion by gravity, volumetric pump or electrical syringe pump and, more often than not, limiting the number of nurse interventions to one or two a day. That much said, the installation of these pumps, which is not systematically justified, entails markedly increased OPAT costs and is liable to expose the patient to a risk of therapeutic failure or adverse effects due to the instability of the molecules utilized in a non-controlled environment, instability that necessitates close monitoring of their use. More precisely, a prescriber must take into consideration the stability parameters of each molecule (infusion duration, concentration following dilution, nature of the diluent and pump temperature). The objective of this work is to evaluate the different means of utilization of elastomeric infusion pumps in intravenous antibiotic administration outside of hospital. Following a review of the literature, we will present a tool for optimized antibiotic prescription, in a town setting by means of an infusion device.

ERASSTRI - European risk assessment study on synthetic turf rubber infill - Part 3: Exposure and risk characterisation.

As the final part of a Europe-wide study on the risk from synthetic turf infill consisting of rubber granules derived from end-of-life tyres (ELT), exposure of sportspeople was assessed and compared with health-based reference values for various chemical substances. Based on information from previous project phases, exposure scenarios were established and exposure was calculated for oral, dermal and inhalation routes. Calculated cancer risks for exposure to polycyclic aromatic hydrocarbons were below 1:1 million. Risk characterisation ratios (RCRs) for non-carcinogenic substances were below 1, indicating no health concerns. For 2-hydroxybenzothiazole no toxicological data were found from which to derive a substance-specific reference value. A threshold-of-toxicological concern approach revealed maximum RCRs slightly above 1, which are acceptable, given the conservativism of the approach. ERASSTRI substantially improved the data available for assessing human health risks from using ELT-derived infill material. Overall, no health concerns could be identified for the use of synthetic turfs with ELT-derived infill material.

Assessment of the stability of citrate-buffered flucloxacillin for injection when stored in two commercially available ambulatory elastomeric devices: INfusor LV (Baxter) and Accufuser (Woo Young Medical): a study compliant with the NHS Yellow Cover Document (YCD) requirements.

Objectives: To investigate the effect of pH and buffers on the degradation rate of flucloxacillin and to determine if flucloxacillin can be stabilised using a buffered diluent for up to 14 days when stored at 2°C-8°C including a 24-hour infusion period at 32°C in two elastomeric devices (Accufuser and INfusor LV) filled to 240 mL. Testing as per the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. Methods: A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of flucloxacillin diluted in 0.3% w/v citrate-buffered saline pH 7.0 when stored at 2°C-8°C in two ambulatory devices (Accufuser and INfusor LV). Flucloxacillin at 10 and 50 mg/mL diluted in 0.3% w/v citrate-buffered saline pH 7.0 to a final volume of 240 mL and stored at 2°C-8°C, including 24 hours at 32°C, was tested from two batches in replicate (n=3) at five time points for up to 14 days according to the requirements of the YCD. Results: Greater than 95% of the zero-time concentration of flucloxacillin at 10 and 50 mg/mL remained when stored at 2°C-8°C after 14 days including 24 hours at 32°C in both Accufuser and INfusor LV devices. Conclusions: Flucloxacillin sodium stability was improved, and complied with UK national standards, by using a diluent of 0.3% w/v citrate-buffered saline pH 7 in both Accufuser and INfusor LV ambulatory devices when filled to 240 mL. The data support assigning a shelf-life of up to 14 days (13 days stored at 2°C-8°C and 24 hours at 32°C). Flucloxacillin may now be used appropriately as a continuous 24-hour infusion in outpatient parenteral antimicrobial therapy services, providing further opportunity to avoid or shorten patient hospital stays, as well as support ideal antimicrobial stewardship principles.

Assessment of Meropenem and Vaborbactam Room Temperature and Refrigerated Stability in Polyvinyl Chloride Bags and Elastomeric Devices.

PURPOSE: Meropenem and vaborbactam is an intravenous beta-lactam/beta-lactamase inhibitor combination antibiotic active against multidrug resistant gram-negative bacteria. It may be a suitable treatment for inpatient and outpatient management of infections, and the intravenous admixture stability is therefore important for optimal utilization. The purpose of this study was to determine the stability of meropenem and vaborbactam in polyvinyl chloride (PVC) infusion bags and elastomeric pumps at room and refrigerated temperatures. METHODS: Meropenem and vaborbactam vials were reconstituted according to manufacturer instructions and diluted in PVC infusion bags to final concentrations of 4, 8, and 16 mg/mL and in elastomeric pumps to 11.4 mg/mL (n = 5 replicates per concentration and per temperature). PVC bags and elastomeric pumps were stored at room temperature (~24 °C) or in the refrigerator (~4 °C) and sampled over 12 and 144 h, respectively. Stability was defined as the duration that meropenem and vaborbactam concentrations remained ≥90% of the original concentrations. FINDINGS: All room temperature replicates across the tested concentrations retained meropenem and vaborbactam stability over 12 h and displayed concentration-dependent degradation. Refrigerated studies resulted in meropenem and vaborbactam stability at all tested concentrations up to 120 h. IMPLICATIONS: Meropenem and vaborbactam in PVC bags (4, 8, and 16 mg/mL) and elastomeric pumps (11.4 mg/mL) were stable for 12 h at room temperature and 120 h when refrigerated. These stability data allow for enhanced flexibility in the preparation, storage, wastage, and administration of meropenem and vaborbactam in the hospital and outpatient setting.

Acute In Vivo Functional Assessment of a Biodegradable Stentless Elastomeric Tricuspid Valve.

Degradable heart valves based on in situ tissue regeneration have been proposed as potentially durable and non-thrombogenic prosthetic alternatives. We evaluated the acute in vivo function, microstructure, mechanics, and thromboresistance of a stentless biodegradable tissue-engineered heart valve (TEHV) in the tricuspid position. Biomimetic stentless tricuspid valves were fabricated with poly(carbonate urethane)urea (PCUU) by double-component deposition (DCD) processing to mimic native valve mechanics and geometry. Five swine then underwent 24-h TEHV implantation in the tricuspid position. Echocardiography demonstrated good leaflet motion and no prolapse and trace to mild regurgitation in all but one animal. Histology revealed patches of proteinaceous deposits with no cellular uptake. SEM demonstrated retained scaffold microarchitecture with proteinaceous deposits but no platelet aggregation or thrombosis. Explanted PCUU leaflet thickness and mechanical anisotropy were comparable with native tricuspid leaflets. Bioinspired, elastomeric, stentless TEHVs fabricated by DCD were readily implantable and demonstrated good acute function in the tricuspid position.

ERASSTRI - European Risk Assessment Study on Synthetic Turf Rubber Infill - Part 1: Analysis of infill samples.

End-of-life tyre (ELT)-derived rubber granules are used as synthetic turf infill on sports fields. They contain various chemical substances and there are concerns that exposure to these substances might be harmful for human health. This Europe-wide risk assessment study addresses these concerns. As the first part, chemical substances in samples from recycling companies and from sports fields were analysed. 86 coated and non-coated ELT granule samples from sites in 14 European countries were investigated, together with ten non-ELT materials. An extensive list of potentially relevant substances was compiled, and the infill materials were analysed for these substances, using GC and HPLC methods. Volatilisation of substances was studied in emission chambers. Polycyclic aromatic hydrocarbons (sum of 8 REACH PAHs) were identified at average concentrations below 10 mg/kg. Substances found at higher concentrations in rubber granules were aluminium (arithmetic mean in uncoated samples from sports fields 5383 mg/kg) and cobalt (168 mg/kg), benzothiazole (48 mg/kg) and 2-hydroxybenzothiazole (34 mg/kg), 6PPD (571 mg/kg) and DPG (51 mg/kg), and 4-tert-octylphenol (14 mg/kg). In addition, the following volatiles were found to evaporate from crumb rubber in emission chambers: benzothiazole, tert-butylamine, cyclohexanone, methyl isobutyl ketone, 2-heptanone and saturated aliphatic hydrocarbons higher than C9. With this comprehensive survey we created a profound database on concentrations of chemical substances in ELT-derived infill material, which is essential for a reliable risk assessment. The results were used to inform subsequent investigations (migration studies, exposure monitoring survey).

ERASSTRI - European Risk Assessment Study on Synthetic Turf Rubber Infill - Part 2: Migration and monitoring studies.

End-of-life tyre (ELT)-derived rubber granules are used as synthetic turf infill on sports fields. They contain various chemical substances and there are concerns that exposure to these substances might be harmful for human health. In this second part of a Europe-wide study to address these concerns migration of substances from rubber granules to artificial body fluids (sweat, saliva, gastric juice) was tested and exposure measurements at sports fields were performed to improve the database for exposure assessment. Some PAHs, aluminium, cobalt, benzothiazole, tert-butylamine, MIBK, 4-tert-octylphenol, bisphenol A, and the phthalates DINP and DEHP were found in at least some samples of sweat simulant. The migration rates calculated with these data were used to inform the dermal exposure assessment. In artificial saliva and gastric juice, only aluminium, cobalt, 4-tert-octylphenol and MIBK were detected and migrated fractions were calculated. Bioaccessibility from rubber granules in the gastrointestinal tract was estimated conservatively, assuming complete availability for most substances. In addition, air samples from 17 sports fields in six European countries were analysed. There were no increased concentrations of metals (aluminium, cobalt), PAHs, or other semivolatile substances in air samples, but some volatiles (MIBK: 95th percentile: 18 µg/m3, benzothiazole: 95th perc.: 7 µg/m3, tert-butylamine: 95th perc.: 31 µg/m3, 2-heptanone: 95th perc.: 0.4 µg/m3, cyclohexanone: 95th perc.: 1.5 µg/m3, and saturated aliphatic hydrocarbons >C9: 95th perc.: 26 µg/m3) were slightly increased in a few samples. In addition, skin wipe samples were obtained from 43 sportspeople after playing on synthetic turfs. Only aluminium was detected above the limit of quantification in these samples (95th perc.: 0.84 mg/sample). These data are important input for risk characterisation as performed in the final study phase. Bioaccessibility data are used for estimating oral and dermal exposure of sportspeople, and air measurements are essential for inhalation exposure assessment.

Development and assessment of a stiffness display system for minimally invasive surgery based on smart magneto-rheological elastomers.

In the present study, a solution to address the clinical need for stiffness display during manual and robotic minimally invasive surgery was postulated, developed, and assessed. To this end, a magneto-rheological elastomer-based stiffness display, MiTouch, was designed, developed, and analyzed. The mechanical properties of the MRE and system parameters were identified experimentally, based on which the force-field-stiffness response surface of the smart MRE was characterized. Based on the response surface, a stiffness controller was designed and verified for a set of performance requirements. A heartbeat simulation experiment showed the capability of the system for replicating desired tactile forces through stiffness control. Also, the system successfully attained an arbitrarily selected stiffness (4 N/mm) and maintained it within a bounded range (4.07 ± 0.41 N/mm). A comparison of the system performance with current literature validated its applicability for the proposed medical application.

Metals and Metalloids Release from Orthodontic Elastomeric and Stainless Steel Ligatures: In Vitro Risk Assessment of Human Exposure.

Elastomeric ligatures are increasingly used as a part of esthetic orthodontic treatment, particularly in children. The aim of the present study was to experimentally test whether these appliances may contribute to exposure to toxic elements. In the present study, elastomeric ligatures (ELs) were incubated in artificial human saliva for 1 month (a typical period of their use) and the release of 21 metals (Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mg, Mo, Ni, Pb, Rb, Tl, Ti, Sb, Sr, Sn, Zn, U, V) and 2 metalloids (As and Ge) was studied using inductively coupled plasma-mass spectrometry. For comparison, stainless steel ligatures (SLs) were incubated for 1, 3, and 6 months (since sometimes their use is prolonged) under similar conditions. The determined metal levels were compared to the corresponding safety limits for human exposure. During 1 month, the ELs released Cd, Co, Cr, Mn, Ni, and Sn at total mean ± SD level of 0.31 ± 0.09, 0.98 ± 0.30, 3.96 ± 1.31, 14.7 ± 8.5, 13.8 ± 4.8, and 49.5 ± 27.7 µg, respectively. Other elements were always below the detection limits. In case of SL, the release of Co, Cr, Fe, Ni, Mn, and Sn was observed, and the determined values increased over the studied period. After 6 months, their total mean ± SD levels amounted to 28.6 ± 0.2, 21.7 ± 0.2, 623.5 ± 3.0, 1152.7 ± 1.8, 5.5 ± 0.3, and 22.6 ± 0.2 µg, respectively. The released metal levels from both ligature types were always below safety limits. The release of Ni from SL during 6 months would constitute 5.0 and 11.5% of tolerable intake in adults and children, respectively. The results of this in vitro study highlight that the use of ligatures in orthodontic treatment can be considered safe in terms of metal exposure although elastic ligatures replaced on a monthly basis appear to be advantageous in comparison to the prolonged use of stainless steel appliances.

Allergic contact dermatitis caused by synthetic rubber gloves in healthcare workers: Sensitization to 1,3-diphenylguanidine is common.

BACKGROUND: The frequency of allergic contact dermatitis has significantly increased in healthcare workers since the transition from latex to synthetic rubber gloves, with 1,3-diphenylguanidine being identified as the most frequently implicated allergen. OBJECTIVES: To highlight the role of 1,3-diphenylguanidine as the culprit allergen in contact allergies to synthetic rubber gloves, to propose recommendations for patch testing, and to discuss alternatives for sensitized subjects. MATERIALS AND METHODS: Patch test data from healthcare workers who developed hand dermatitis after wearing rubber gloves and who reacted positively to glove samples and rubber additives were collected from September 2010 to December 2017 in a Belgian hospital. RESULTS: A total of 44 caregivers were included in this study. Patch tests showed that: (a) 84% of the study population reacted positively to carba mix; (b) 86% reacted positively to 1,3-diphenylguanidine; and (c) 13 (30%) reacted positively to thiuram mix. Half of the subjects reacted positively to gloves containing 1,3-diphenylguanidine, whereas none reacted to accelerator-free gloves. CONCLUSION: The most commonly identified allergen was 1,3-diphenylguanidine, far ahead of thiurams, which were previously described as the most sensitizing accelerators. The use of 1,3-diphenylguanidine-free gloves is recommended. No subject reacted to gloves without accelerators, thus confirming their efficiency among accelerator-sensitized patients. We recommend that 1,3-diphenylguanidine be added to the European baseline series.

In vivo functional assessment of a novel degradable metal and elastomeric scaffold-based tissue engineered heart valve.

OBJECTIVE: Ideal heart valve solutions aim to provide thrombosis-free durability. A scaffold-based polycarbonate urethane urea tissue-engineered heart valve designed to mimic native valve microstructure and function was used. This study examined the acute in vivo function of a stented tissue-engineered heart valve in a porcine model. METHODS: Trileaflet valves were fabricated by electrospinning polycarbonate urethane urea using double component fiber deposition. The tissue-engineered heart valve was mounted on an AZ31 magnesium alloy biodegradable stent frame. Five 80-kg Yorkshire pigs underwent open tissue-engineered heart valve implantation on cardiopulmonary bypass in the pulmonary position. Tissue-engineered heart valve function was echocardiographically evaluated immediately postimplant and at planned study end points at 1, 4, 8, and 12 hours. Explanted valves underwent biaxial mechanical testing and scanning electron microscopy for ultrastructural analysis and thrombosis detection. RESULTS: All 5 animals underwent successful valve implantation. All were weaned from cardiopulmonary bypass, closed, and recovered until harvest study end point except 1 animal that was found to have congenital tricuspid valve dysplasia and that was euthanized postimplant. All 5 cases revealed postcardiopulmonary bypass normal leaflet function, no regurgitation, and an average peak velocity of 2 m/s, unchanged at end point. All tissue-engineered heart valve leaflets retained microstructural architecture with no platelet activation or thrombosis by scanning electron microscopy. There was microscopic evidence of fibrin deposition on 2 of 5 stent frames, not on the tissue-engineered heart valve. Biaxial stress examination revealed retained postimplant mechanics of tissue-engineered heart valve fibers without functional or ultrastructural degradation. CONCLUSIONS: A biodegradable elastomeric heart valve scaffold for in situ tissue-engineered leaflet replacement is acutely functional and devoid of leaflet microthrombosis.

Assessment of Extractable Elements from Elastomers.

Compendia methods have historically been used to assess heavy metals in both drug products and packaging material extracts. However, these methods have been found to be inadequate for elemental specificity and accurate measurements. The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) has published the Q3D, Guideline for Elemental Impurities, to provide a risk-based approach that specifies elements to be considered in a drug product risk assessment and permitted daily exposures (PDEs) depending on toxicological concern and route of administration. Consistent with these efforts, the United States Pharmacopeia (USP) withdrew the <231> Heavy Metals test procedure as of January 2018. The USP published new methods consistent with ICH Q3D risk-based approaches, <232> Elemental Impurities - Limits and <233> Elemental Impurities - Procedures. These new tests are intended for evaluation of drug products, leaving a gap in the assessment of extractable elements for packaging components. This gap prompted the need for a better understanding of the potential for elements of concern to extract from packaging materials and contribute to drug product elemental impurities. The present study investigated multiple extraction conditions coupled with modern analytical techniques to understand the capacity for elements to extract from elastomeric components. Most elements of interest, based on ICH or their potential for occurrence in elastomers, were ultimately recovered at levels below designated thresholds, allowing for correlation to PDE. These results highlight that although extractable elements from elastomeric components have the potential to contribute elemental impurities to a drug product, the actual contribution to cumulative levels would need to be calculated among all other potential sources as part of the process of elemental impurities assessment.LAY ABSTRACT: Compendia methods have historically been used to assess heavy metals in final drug products and extracts from packaging materials. However, these methods were found to provide inadequate data to address the evolving risk concerns of elemental impurities in drug products and their potential toxic effects. The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use member countries are working toward implementing a risk-based approach that specifies elements to be considered in a drug product safety assessment and permitted daily exposures. The United States Pharmacopeia is coordinating with this goal by withdrawing the traditional procedure and replacing it with the tests that can inform safety risk assessments. However, the new tests are intended for evaluation of only final drug products, leaving a gap in the assessment of extractable elements for packaging components. The present study addressed this gap by focusing on elastomeric components used in injectable packaging systems and exploring appropriate elastomeric extraction methods coupled with modern analytical techniques to better understand the full potential for elements to extract from elastomers and contribute to the elemental impurity profile of a drug product.

3D Printed Surgical Simulation Models as educational tool by maxillofacial surgeons.

INTRODUCTION: The aim of this study was to evaluate whether inexpensive 3D models can be suitable to train surgical skills to dental students or oral and maxillofacial surgery residents. Furthermore, we wanted to know which of the most common filament materials, acrylonitrile butadiene styrene (ABS) or polylactic acid (PLA), can better simulate human bone according to surgeons' subjective perceptions. MATERIALS AND METHODS: Upper and lower jaw models were produced with common 3D desktop printers, ABS and PLA filament and silicon rubber for soft tissue simulation. Those models were given to 10 blinded, experienced maxillofacial surgeons to perform sinus lift and wisdom teeth extraction. Evaluation was made using a questionnaire. RESULTS: Because of slightly different density and filament prices, each silicon-covered model costs between 1.40-1.60 USD (ABS) and 1.80-2.00 USD (PLA) based on 2017 material costs. Ten experienced raters took part in the study. All raters deemed the models suitable for surgical education. No significant differences between ABS and PLA were found, with both having distinct advantages. CONCLUSION: The study demonstrated that 3D printing with inexpensive printing filaments is a promising method for training oral and maxillofacial surgery residents or dental students in selected surgical procedures. With a simple and cost-efficient manufacturing process, models of actual patient cases can be produced on a small scale, simulating many kinds of surgical procedures.