We propose the nasal administration of calcium-enriched physiological salts as a new hygienic intervention with possible therapeutic application as a response to the rapid and tenacious spread of COVID-19. We test the effectiveness of these salts against viral and bacterial pathogens in animals and humans. We find that aerosol administration of these salts to the airways diminishes the exhalation of the small particles that face masks fail to filter and, in the case of an influenza swine model, completely block airborne transmission of disease. In a study of 10 human volunteers (5 less than 65 years and 5 older than 65 years), we show that delivery of a nasal saline comprising calcium and sodium salts quickly (within 15 min) and durably (up to at least 6 h) diminishes exhaled particles from the human airways. Being predominantly smaller than 1 μm, these particles are below the size effectively filtered by conventional masks. The suppression of exhaled droplets by the nasal delivery of calcium-rich saline with aerosol droplet size of around 10 μm suggests the upper airways as a primary source of bioaerosol generation. The suppression effect is especially pronounced (99%) among those who exhale large numbers of particles. In our study, we found this high-particle exhalation group to correlate with advanced age. We argue for a new hygienic practice of nasal cleansing by a calcium-rich saline aerosol, to complement the washing of hands with ordinary soap, use of a face mask, and social distancing.

The ability to control the movement of molecules is both fascinating scientifically as well as being critically important to the well-being of our planet and its people. In particular, the sustained release of molecules over prolonged periods at controlled rates has had and will continue to have enormous implications for the delivery of substances in medicine, agriculture, the environment, nutrition, aquaculture, household consumer products, and numerous other areas. This field is advancing at a rapidly accelerating pace. In this article, I largely discuss our own work, starting 45 years ago, in enabling the controlled release of macromolecules from biocompatible polymers. I also discuss the synthesis of novel materials to affect molecular movement and I then examine external approaches for controlling the movement of molecules through materials, using forces such as electric, acoustic, and magnetic fields. I further discuss approaches for controlling molecular movement through physiologic barriers, such as the skin, lung, and intestine. Finally, I outline several future areas of this field, including how it can affect the developing world, the ability to control the movement of molecules into mammalian cells, and the design of intelligent approaches to control molecular delivery.

Materials chemistry has been fundamental to the enormous field that encompasses the delivery of molecules both to desired sites and/or at desired rates and durations. The field encompasses the delivery of molecules including fertilizers, pesticides, herbicides, food ingredients, fragrances and biopharmaceuticals. A personal perspective is provided on our early work in this field that has enabled the controlled release of ionic substances and macromolecules. Also discussed are new paradigms in creating biomaterials for human use, the non-invasive delivery of molecules through the skin and lungs, the development of intelligent delivery systems and extensions to nanomedicine. With the advent of potentially newer biopharmaceutics such as siRNA, mRNA and gene editing approaches and their use being limited by delivery, future research in this field may be more critical than ever before.

Biodegradable polymers with high mechanical strength, flexibility and optical transparency, optimal degradation properties and biocompatibility are critical to the success of tissue engineered devices and drug delivery systems. In this work, microfluidic devices have been fabricated from elastomeric scaffolds with tunable degradation properties for applications in tissue engineering and regenerative medicine. Most biodegradable polymers suffer from short half life resulting from rapid and poorly controlled degradation upon implantation, exceedingly high stiffness, and limited compatibility with chemical functionalization. Here we report the first microfluidic devices constructed from a recently developed class of biodegradable elastomeric poly(ester amide)s, poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)s (APS), showing a much longer and highly tunable in vivo degradation half-life comparing to many other commonly used biodegradable polymers. The device is molded in a similar approach to that reported previously for conventional biodegradable polymers, and the bonded microfluidic channels are shown to be capable of supporting physiologic levels of flow and pressure. The device has been tested for degradation rate and gas permeation properties in order to predict performance in the implantation environment. This device is high resolution and fully biodegradable; the fabrication process is fast, inexpensive, reproducible, and scalable, making it the approach ideal for both rapid prototyping and manufacturing of tissue engineering scaffolds and vasculature and tissue and organ replacements.

Rapidly rotating stars are readily produced in binary systems. An accreting star in a binary system can be spun up by mass accretion and quickly approach the break-up limit. Mergers between two stars in a binary are expected to result in massive, fast rotating stars. These rapid rotators may appear as Be or Oe stars or at low metallicity they may be progenitors of long gamma-ray bursts.

Given the high frequency of massive stars in close binaries it seems likely that a large fraction of rapidly rotating stars result from binary interaction. It is not straightforward to distinguish a a fast rotator that was born as a rapidly rotating single star from a fast rotator that resulted from some kind of binary interaction. Rapidly rotating stars resulting from binary interaction will often appear to be single because the companion tends to be a low mass, low luminosity star in a wide orbit. Alternatively, they became single stars after a merger or disruption of the binary system during the supernova explosion of the primary.

The absence of evidence for a companion does not guarantee that the system did not experience binary interaction in the past. If binary interaction is one of the main causes of high stellar rotation rates, the binary fraction is expected to be smaller among fast rotators. How this prediction depend on uncertainties in the physics of the binary interactions requires further investigation.

Two strategies for vaccine-delivery systems, both relying on concepts of controlled-release technology, are described in this review. The first strategy involves using biodegradable polymer microspheres for parenteral and oral delivery of antigens. The other strategy combines two technologies, the encapsulation of antigen within liposomes and liposome encapsulation in hydrogels, to protect them from a rapid degradation in vivo. Both strategies have shown promise in terms of increasing the immunogenicity of poorly immunogenic peptides and protein vaccines. The microencapsulation process, antigen stability, mechanism of antigen release, and optimal release kinetics for vaccine delivery are reviewed, and the strengths and weaknesses of each approach are discussed.

In Latin America missions have traditionally played a large role in conquering and incorporating native populations into dominant society. Most studies of the missionary enterprise have focused on the colonial period, when the missions reached their high point. The Jesuit missions in Paraguay and the Franciscan missions of central and northern Mexico, for example, ruled over vast territories and thousands of Indians. Although these institutions and their leaders have been widely studied because of their importance and visibility for colonial Latin America, it is not often recognized that missions continued to play a crucial role in the frontier development of the region even after the Spanish and Portuguese had been driven from the continent. Throughout the republican period, missionaries from many orders and creeds became critically important actors who, to a large degree, determined the shape of relations between native peoples and national society. This is quite clear even today in the Amazon basin, where missionaries often provide the natives' first exposure to Europeanized society.

Cell encapsulation has been broadly investigated as a technology to provide immunoprotection for transplanted endocrine cells. Here we develop a new fabrication method that allows for rapid, homogenous microencapsulation of insulin-secreting cells with varying microscale geometries and asymmetrically modified surfaces. Micromolding systems were developed using polypropylene mesh, and the mesh material/surface properties associated with efficient encapsulation were identified. Cells encapsulated using these methods maintain desirable viability and preserve their ability to proliferate and secrete insulin in a glucose-responsive manner. This new cell encapsulation approach enables a practical route to an inexpensive and convenient process for the generation of cell-laden microcapsules without requiring any specialized equipment or microfabrication process.

Since the middle of the 90's, GaN epitaxy techniques have been developed, using either MOCVD or MBE growth methods. A low cost approach is presented aiming at satisfying thermal issues encountered on conventional substrates such as SiC, Sapphire and more recently Silicon. Domain of application are being covered with their associated challenges: RF and High Power applications. Stress engineering is one of the key parameters.

The following article is an edited transcript based on the Von Hippel Award presentation by Robert Langer of the Massachusetts Institute of Technology on November 30, 2005, at the Materials Research Society Fall Meeting in Boston. Langer was honored with MRS's highest award for his “pioneering accomplishments in the science and application of biomaterials in drug delivery and tissue engineering, particularly in inventing the use of materials for protein and DNA delivery, and for his achievements in interdisciplinary research which have generated new medical products, created new fields of biomaterials science, and inspired research programs throughout the world.”

Recent progress in various biotechnology fields, such as microfluidics, tissue engineering, and cellular biology, has created a great demand for substrates that can undergo defined remodeling with time. As a result, the latest research on materials with dynamically controllable surface properties has led to a variety of novel smart surface designs.

Magnetic responsive particles were designed for use in oral delivery of insulin. Magnetite nanoparticles (12 nm average size) were synthesized and co-encapsulated with insulin into poly(lactide-co-glycolide) (PLGA) microparticles (4.6 ± 2.2 μm average particle size) through the double-emulsion method. The spherical structures of resulting microparticles were well maintained at magnetite content 5 wt % or less. Mice were gavaged with 125I-insulin-magnetitePLGA microparticles and a circumferential trans-abdominal magnetic field was applied forty minutes after administration to retard the transit of the microparticles in the intestinal tract. As control, mice were similarly dosed without the subsequent trans-abdominal magnetic field. Mice were sacrificed, and the intestinal radioactivity was 101% and 145% higher in treated mice versus the control at 6 h and 12 h, respectively. A single administration of 50 unit/kg Humulin Rmagnetite-PLGA microparticles to the fasted mice resulted in 66% reduction of blood glucose level in the presence of external magnetic field at 12 h, compared to 27% reduction in the absence of magnetic field.

Nanocomposite materials consisting of colloidal gold (Au) nanoparticles embedded in thermo-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogels are synthesized. Thiol groups that bind to both Au3+ ions and colloidal Au are incorporated into the side-chains of the PNIPAm hydrogels through copolymerization. This report describes formation of morphologically well-defined Au nanoparticles with varying long-term stability inside the hydrogel matrices containing adjustable concentrations of thiols. Compared with the non-Au containing PNIPAm hydrogels, the Au-PNIPAm nanocomposite hydrogels have shown higher degrees of equilibrium swelling and different temperature-triggered phase transitions. It is hypothesized that these remarkable changes in hydrogel bulk properties are related to the different morphologies and sizes, and possibly the amount of surface charges, of the Au nanoparticles.

Biodegradable polymers have significant potential in biotechnology and bioengineering. However, for some applications, they are limited by their inferior mechanical properties and unsatisfactory compatibility with cells and tissues. A strong, biodegradable, and biocompatible elastomer could be useful for fields such as tissue engineering, drug delivery, and in vivo sensing [1, 2]. We designed, synthesized, and characterized a tough biodegradable elastomer from biocompatible monomers. This elastomer forms a covalently crosslinked three-dimensional network of random coils with hydroxyl groups attached to its backbone. Both crosslinking and the hydrogen bonding interactions between the hydroxyl groups likely contributes to the unique properties of the elastomer. In vitro and in vivo studies show the polymer has good biocompatibility. Subcutaneous (SC) polymer implants are absorbed completely within 60 days with restoration of the implantation sites to their normal architecture.

Conductive polymers such as polypyrrole (Ppy) are potentially useful as an active interface for altering cellular processes and function. Their utilization in medically related applications however have been substantially held back by their non-degradable nature. Herein we report a novel approach to creation of bioerodible polypyrroles via modification of pyrrole beta-carbon with an ionizable moiety. It has been shown that the erosion rate of acid-bearing derivative of polypyrrole increases with pH, which is consistent with the pH dependent ionization of carboxylic acid group. The novel paradigm proposed for the creation of bioerodible polypyrroles allows for simple and efficient control over the erosion rate of the substrate independent of the polymer chain length, via the choice of the terminal ionizable group and its concentration along the polymer backbone.

A dual scaffold structure made of biodegradable polymers and seeded with neural stem cells has been developed to address the issues of spinal cord injury including axonal severance and the loss of neurons and glia. The general design of the scaffold is derived the structure of the spinal cord with an outer section which mimics the white matter with long axial pores to provide axonal guidance and an inner section seeded with neural stem cells to address the issues of cell replacement and mimic the general character of the gray matter. The seeded scaffold leads to improved functional recovery as compared with the lesion control or cells alone following spinal cord injury.

The following is an edited transcript of the plenary lecture presented by Robert Langer at the 1995 MRS Spring Meeting on April 17, 1995 in San Francisco.

Over the last 21 years I have been involved in examining and studying, and in some cases synthesizing new polymers and biomaterials, looking at how they might be able to solve two problems. One set of problems involves drug delivery; a second involves creating new tissues.

Controlled drug release is a relatively young field that has involved a fundamental change in the way drugs are delivered. Transdermal drug delivery, for example, uses five layers of polymers, yet the whole system is 0.2 mm thick. One such polymer contains nitroglycerine, which is slowly released for one day from a patch through the skin into the blood circulation. This process provided a novel way to treat angina for patients with chest pains. First introduced in 1982, such drug-delivery systems saw a usage rate of over 500 million last year.

Norplant systems, which are silicone capsules placed under the forearm, slowly release a birth-control drug for over 2,000 days, or five years, from what are actually six small implants about the size of match sticks. These two examples illustrate that drugs can be made to slowly diffuse through polymers over a long period of time.

Novel polymers with good mechanical properties are being developed as degradable matrices for bone growth and regeneration. The poly(anhydride-co-imides) were synthesized from trimellitylimidoglycine and 1,6-bis(p-carboxyphenoxy)hexane in molar compositions of 10:90, 30:70 and 50:50. These polymers have compressive strengths (23–57 MPa), which are similar to human cortical bone. 1 In vitro degradation was performed under acidic (pH 5), physiological (pH 7.4), and basic (pH 10) conditions. The degradation rate increased under basic conditions and by increasing the amount of trimellitylimidoglycine in the polymer backbone. Two erosion zones were observed in the polymers by microscopy. In vivo polymer degradation was evaluated by characterizing polymer discs implanted in subcutaneous tissue of rats over a 56 day time period. Copolymers with the highest ratio of trimellitylimidoglycine in the polymer backbone were completely degraded by 56 days, the other compositions remained in the tissue as solid pellets at this time. In vivo degradation was much slower than the corresponding in vitro degradation.

Biodegradable polymer scaffolds have been used to engineer new tissues or organs by culturing cells on them. The degradation, structure and properties of fibrous nonwoven poly(glycolic acid) (PGA) scaffolds (2 mm thick and 10 mm in diameter) were studied over 9 weeks in tissue culture medium at 37°C under mixing condition. After 3 days of in vitro culture, the mass of the scaffolds increased slightly (5.6%) due to hydration and/or adsorption, but it decreased thereafter. After 9 weeks, only 12.5% of the mass were retained. The melting point of the scaffolds decreased from 218.1°C to 186.0°C in the first 3 weeks, as measured with differential scanning calorimetry (DSC). No melting peak could be identified for later times (6 weeks and 9 weeks). The crystallinity of the scaffolds doubled over the first 11 days, but decreased thereafter. The glass transition temperature of the degrading scaffolds (36–39°C) was lower than that of the dry starting scaffolds (40°C) presumably due to the plasticizing effect of absorbed water and other low molecular weight molecules. The PGA scaffolds without cells lost their structural integrity and mechanical strength completely in 2 to 3 weeks. In contrast, the neocartilage constructs regenerated from the PGA scaffolds and bovine chondrocytes kept their structural integrity throughout the in vitro culture study. After 12 weeks of in vitro culture, the biomechanical properties of the neocartilage constructs reached the same orders of magnitude as those of normal bovine cartilage.