Ultrapure N2 gas was bubbled through water, and the humidified output containing undetectable concentrations of ozone filled a closed chamber in which 18 MΩ-cm water was sprayed through a silica capillary to form microdroplets. Analysis of the collected microdroplets by NMR spectroscopy showed the presence of hydrogen peroxide at a concentration level ranging from 0.3 to 1.5 μM depending on the flow conditions. This was confirmed using a spectrofluorometric assay. We suggest that this finding establishes that when sprayed to form microdroplets, water has the ability to produce hydrogen peroxide by itself. When the N2 gas is replaced by compressed air or O2 gas, the concentration of hydrogen peroxide is found to increase, indicating that gas–surface interactions with O2 in aqueous microdroplets promote the formation of hydrogen peroxide.

Next generation engineered tissue constructs with complex and ordered architectures aim to better mimic the native tissue structures, largely due to advances in 3D bioprinting techniques. Extrusion bioprinting has drawn tremendous attention due to its widespread availability, cost‐effectiveness, simplicity, and its facile and rapid processing. However, poor printing resolution and low speed have limited its fidelity and clinical implementation. To circumvent the downsides associated with extrusion printing, microfluidic technologies are increasingly being implemented in 3D bioprinting for engineering living constructs. These technologies enable biofabrication of heterogeneous biomimetic structures made of different types of cells, biomaterials, and biomolecules. Microfluiding bioprinting technology enables highly controlled fabrication of 3D constructs in high resolutions and it has been shown to be useful for building tubular structures and vascularized constructs, which may promote the survival and integration of implanted engineered tissues. Although this field is currently in its early development and the number of bioprinted implants is limited, it is envisioned that it will have a major impact on the production of customized clinical‐grade tissue constructs. Further studies are, however, needed to fully demonstrate the effectiveness of the technology in the lab and its translation to the clinic.

Micro and nanocarriers Micro and nanoscale technologies Oral drug delivery Tissue models Oral administration is a pillar of the pharmaceutical industry and yet it remains challenging to administer hydrophilic therapeutics by the oral route. Smart and controlled oral drug delivery could bypass the physiological barriers that limit the oral delivery of these therapeutics. Micro-and nanoscale technologies, with an unprecedented ability to create, control, and measure micro-or nanoenvironments, have found tremendous applications in biology and medicine. In particular, significant advances have been made in using these technologies for oral drug delivery. In this review, we briefly describe biological barriers to oral drug delivery and micro and nanoscale fabrication technologies. Micro and nanoscale drug carriers fabricated using these technologies, including bioadhesives, microparticles, micropatches, and nanoparticles, are described. Other applications of micro and nanoscale technologies are discussed, including fabrication of devices and tissue engineering models to precisely control or assess oral drug delivery in vivo and in vitro, respectively. Strategies to advance translation of micro and nanotechnologies into clinical trials for oral drug delivery are mentioned. Finally, challenges and future prospects on further integration of micro and nanoscale technologies with oral drug delivery systems are highlighted.

This paper investigates how organization should design their supply chains (SCs) and use risk mitigation strategies to meet different performance objectives. To do this, we develop two mixed integer nonlinear (MINL) lean and responsive models for a four-tier SC to understand these four strategies: i) holding back-up emergency stocks at the DCs, ii) holding back-up emergency stock for transshipment to all DCs at a strategic DC (for risk pooling in the SC), iii) reserving excess capacity in the facilities, and iv) using other facilities in the SC's network to back-up the primary facilities. A new method for designing the network is developed which works based on the definition of path to cover all possible disturbances. To solve the two proposed MINL models, a linear regression approximation is suggested to linearize the models; this technique works 2 based on a piecewise linear transformation. The efficiency of the solution technique is tested for two prevalent distribution functions. We then explore how these models operate using empirical data from an automotive SC. This enables us to develop a more comprehensive risk mitigation framework than previous studies and show how it can be used to determine the optimal SC design and risk mitigation strategies given the uncertainties faced by practitioners and the performance objectives they wish to meet.

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Background: A transdermal patch for delivery of Levonorgestrel (LNG) can be used for long-acting contraception. Objective: In this study, we designed and characterized a patch made of nonwoven electrospun microfibers comprised of Polycaprolactone (PCL) encapsulating LNG for slow release in a mineral oil matrix. Methods and Results: Scanning electron microscopy showed uniform, randomly oriented PCL fibers with large interconnected voids filled with mineral oil. Thermogravimetric analysis indicated that LNG loaded into PCL fibers had thermal stability up to ~200°C. Differential Scanning Calorimetry suggested that LNG was dispersed in the electrospun fibers without interaction between the LNG and PCL, and without formation of drug crystals. Fourier Transform Infrared spectroscopy and X-ray diffraction results further supported the conclusion that there was no chemical drug–polymer interaction in LNGloaded fibers. Effective in vitro flux (i) from patches into mineral oil was 1.9 µgcm-2h-1, (ii) from mineral oil across porcine skin was 4.6 µgcm-2h-1 and (iii) from patches across porcine skin was 1.7 μgcm- 2h-1, indicating that transdermal delivery rate was controlled by a combination of the patch and the skin. Conclusion: The LNG-loaded patches demonstrated steady delivery of LNG across skin for up to 5 days in vitro. With additional development, LNG-loaded electrospun PCL patches could be used for long-acting contraception.

Bacterial and fungal pathogens have caused serious problems to the human health. This is particularly true for untreatable infectious diseases and clinical situations where there is no reliable treatment for infected patients. To increase the antimicrobial activity of materials, we introduce silver nanoparticle (NP) patches in which the NPs are incorporated to the surface of smooth and uniform poly(acrylic acid) (PAA) nanofibers. The PAA nanofibers were thermally crosslinked with ethylene glycol via heat treatment through a mild method. The characterization of the resulting PAA-silver NP patches was done using scanning electron microscopy (SEM), UV spectroscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). To demonstrate the antimicrobial activity of PAA, we incorporated the patches containing the silver NPs into strains of fungi such as Candida albicans (C. albican) and bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA). The PAA-silver fibers achieved zones of inhibition against C. albicans and MRSA indicating their antimicrobial activity against both fungi and bacteria. We conclude that silver NP patches exhibited multiple inhibitory actions for the interruption and blockage of activity fungal and bacterial strains, which has the potential as an antimicrobial agent in infectious diseases. Moreover, the proposed material has the potential to be used in antimicrobial textile fabrics, food packaging films, and wound dressings.

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